Download 2000 Drug Trend Report

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EXPRESS SCRIPTS
june 2001
www.express-scripts.com
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T H E B OT TO M L I N E
Per member per year (PMPY) Average Wholesale Price (AWP) ingredient costs rose by 16.2 percent in 2000.
This marks the first time since Express Scripts began monitoring drug cost trends in 1993 that the annual
rate of PMPY drug cost increase slowed from the previous year. Over the next five years, it is projected that
PMPY drug costs will increase by 81 percent.
Acknowledgements: The authors owe special thanks to the following people who provided substantial
input and comments: Brian Ellis, BS ; Michelle Farmer, PharmD; Raulo Frear, PharmD; Mark Frisse, MD;
Andrew Goggin, MD; Doug Mager, BS; Chris Peterson, PharmD; Mark Roddy, MHA, CPA; Trey Springer, CPhT;
Yakov Svirnovskiy, MA; Regina Thompson, BA; Belinda Wilkins; and Clinical Services staff.
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Page A
E X P R E S S S C R I P TS
2000
Drug Trend
re p o r t
june 2001
Fred Teitelbaum, PhD
Ruth Martinez, RPh
Andrew Parker, MBA
Rochelle Henderson, MPA
Brian Kolling, PharmD
Catherine Roe, PhD
Sandy Ellis, RPh
© Express Scripts, Inc. June 2001 All Rights Reserved
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TABLE OF
CONTENTS
TABLE OF
CONTENTS
22501_ii58
TA B L E O F C O N T E N T S
VI
1
INTRODUCTION
3
3
SUMMARY OF FINDINGS
134
134
135
136
139
141
143
145
146
APPENDIX B: DRUG UTILIZATION AND COST BY SEX AND AGE
Methods
Utilization of Each Therapy Class by Sex and Age
Gastrointestinals
Central Nervous System
Cardiovascular
Inflammation and Pain Management
Respiratory
Anti-Infectives
Women’s Health
Other
PREFACE
124
Between 1996 and 2000
Between 1999 and 2000
2001 Through 2005 Projections
5
METHODS
7
8
TRENDS IN EXPENDITURES FOR PRESCRIPTION DRUGS
12
13
16
20
21
Changes in Common Drug Costs Between 1998 and 1999;
Utilization of Common Drugs
AWP Ingredient Cost Per Prescription
Inflation
Therapeutic Mix and Strength Mix
Units per Rx
New Drugs
TABLES
7
9
TRENDS IN
EXPENDITURES
TRENDS IN
EXPENDITURES
INTRODUCTION
4
4
INTRODUCTION
123
PREFACE
PREFACE
TABLE 1: Components of Per Member Per Year AWP Cost Trend 1996-2000
TABLE 2: Utilization of Common Drugs of Top 25 Therapy Classes
1999-2000 Ranked by 2000 Rxs Per Member Per Year
14
TABLE 3: Price Changes Due to Inflation of Top 25 Therapy Classes 1999-2000
15
17
20
TABLE 4: Price Changes for Top 50 Common Brand Drugs 1999-2000
TABLE 5: Price Changes Due to Mix of Top 25 Therapy Classes 1999-2000
TABLE 6: Price Changes Due to Changes in Units Per Prescription 1999-2000,
22
24
28
46
TABLE
TABLE
TABLE
TABLE
60
TABLE A1: Cost Per Prescription and Per Member Per Year Cost for Major Therapy
DRUG
IMPORTANCE
ACTIONS
THE GROWING IMPORTANCE OF PRESCRIPTION DRUGS IN DISEASE TREATMENT
51
51
52
52
57
ACTIONS TO MITIGATE IMPACT OF COST TREND PER PRESCRIPTION
Top 25 Therapy Classes by Prescriptions in 2000
Classes, 1998-1999
APPENDIX A: DRUG THERAPY CLASS REVIEW
Gastrointestinals
Central Nervous System
Inflammation and Pain Management
Cardiovascular
Respiratory
Anti-Infectives
Women’s Health
Dermatologicals
Antidiabetics
Anticancer
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
124
126
127
130
131
TABLE
TABLE
TABLE
TABLE
TABLE
B1: Most Frequently Used Therapy Classes by Sex
B2: Most Frequently Used Therapy Classes by Age
B3: Most Frequently Used Therapy Classes by Sex and Age
B4: Overall Drug Utilization by Sex and Age
B5: Percent of Total AWP, Mean AWP Per Prescription and Percent Change in Mean
AWP Prescription by Sex and Age Groups
III
APPENDIX B
II
Drugs and Other Medical Services for Selected Medical Conditions
APPENDIX A
59
61
64
70
78
86
93
103
109
111
115
Actions Aimed at Controlling Per Prescription Costs
Reducing Utilization of Prescription Drugs
Reducing Per Prescription Costs and Utilization
Defined Benefit Contribution and Member Choice
7: Top New Drugs in 2000
8: Percent of 2000 Cost and AWP Cost Per Prescription for Top 50 New Drugs
9: Drug Trends: All Drugs 1999-2000 Summary and 2001-2005 Forecast
10: 1998-1999 Percent Change in Per Member Per Year Covered Charges for
ACTIONS
APPENDIX A
39
DRUG
IMPORTANCE
APPENDIX B
2000 DRUG COST TREND FORECAST
COST
FORECAST
COST
FORECAST
Ranked by Percent Change in Price
25
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TABLE OF
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TABLE OF
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INTRODUCTION
TRENDS IN
EXPENDITURES
COST
FORECAST
DRUG
IMPORTANCE
ACTIONS
APPENDIX A
FIGURE 10:
FIGURE 11:
48
53
FIGURE 12:
FIGURE 13:
56
FIGURE 14:
62
67
69
71
FIGURE
FIGURE
FIGURE
FIGURE
A1:
A2:
A3:
A4:
73
75
76
80
81
82
84
87
89
91
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
A5:
A6:
A7:
A8:
A9:
A10:
A11:
A12:
A13:
A14:
92
96
97
98
FIGURE
FIGURE
FIGURE
FIGURE
A15:
A16:
A17:
A18:
IV
Therapy Class Drug Market Share Trend — Gastrointestinals
Therapy Class Drug Market Share Trend — Antidepressants
Therapy Class Drug Market Share Trend — Antianxiety Agents
Therapy Class Drug Market Share Trend — Anti-Rheum (NSAIDS
and COX-2s)
Therapy Class Drug Market Share Trend — Narcotic Analgesics
Therapy Class Drug Market Share Trend — Migraine Products
Therapy Class Drug Market Share Trend — Anticonvulsants
Therapy Class Drug Market Share Trend — Antihypertensives
Therapy Class Drug Market Share Trend — Calcium Blockers
Therapy Class Drug Market Share Trend — Beta Blockers
Therapy Class Drug Market Share Trend — Antihyperlipidemics
Therapy Class Drug Market Share Trend — Antiasthmatics
Therapy Class Drug Market Share Trend — Antihistamines
Therapy Class Drug Market Share Trend — (Decongestants)
Nasal Steroids
Therapy Class Drug Market Share Trend — Cough/Cold
Therapy Class Drug Market Share Trend — Cephalosporins
Therapy Class Drug Market Share Trend — Macrolides
Therapy Class Drug Market Share Trend — Penicillins
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
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137
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139
140
141
141
142
142
143
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144
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148
149
150
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
B1:
B2:
B3:
B4:
B5:
B6:
B7:
B8:
B9:
B10:
B11:
B12:
B13:
B14:
B15:
B16:
B17:
B18:
B19:
B20:
B21:
B22:
B23:
B24:
B25:
B26:
B27:
Percent of Prescriptions Filled by Members of Each Sex and Age Category
Mean AWP Percent Change from 1999 to 2000 by Sex and Age
Gastrointestinals
Antidepressants
Antianxiety Agents
Antihypertensives
Calcium Blockers
Beta Blockers
Antihyperlipidemics
Anti-rheumatics
Narcotic Analgesics
Migraine Products
Antiasthmatics
Antihistamines
Decongestants
Cough/Cold Products
Penicillins
Cephalosporins
Macrolides
Oral Contraceptives
Estrogens
Dermatologicals
Antidiabetics
Anticancer
Antivirals
Anticonvulsants
Antifungals
V
APPENDIX B
APPENDIX B
44
45
5:
6:
7:
8:
9:
Therapy Class Drug Market Share Trend — Antivirals
Therapy Class Drug Market Share Trend — Oral Contraceptives
Therapy Class Drug Market Share Trend — Estrogens
Therapy Class Drug Market Share Trend — Miscellaneous Endocrines
Therapy Class Drug Market Share Trend — Dermatologicals
Therapy Class Drug Market Share Trend — Oral Hypoglycemics
Therapy Class Drug Market Share Trend — Insulins
Therapy Class Drug Market Share Trend — Anticancer
APPENDIX A
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
A19:
A20:
A21:
A22:
A23:
A24:
A25:
A26:
ACTIONS
22
23
26
27
40
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
FIGURE
DRUG
IMPORTANCE
FIGURE 2:
FIGURE 3:
FIGURE 4:
99
104
106
107
109
112
113
118
COST
FORECAST
2
7
12
National Health Expenditures as a Percent of GDP and Percent of
Population 65 and Older, 1980-2010
Average Annual Percentage Growth from Previous Year
Per Member Per Year AWP Costs 1996-2000
Percent of AWP Change Attributed to Inflation, Units, Theraputic Mix and
Strength Mix 1999-2000
Impact of New Drugs Introduced Since 1992 on 2000 Utilization and Cost
Percent of AWP Accounted for by New Drugs
Per Member Per Year AWP 1996-2005
Percent Change in PMPY AWP Cost 1995-2005
Prescription Drugs, Hospital Care and Physician and Clinical Services as
a Percentage of National Healthcare Expenditures 1980-2010
Summary Changes in Treatments for Selected Diseases
Per Member Per Year Covered Charges for Drugs and Other Medical
Services 1998-1999
Length of Treatment in Any Prescription in Selected Therapy Classes
Increases in Average Prescription Cost From 1996 to 2000
by Therapy Class
Generic Fill Rate and Generic AWP per Prescription for Selected
Therapy Classes 2000
TRENDS IN
EXPENDITURES
FIGURE 1:
INTRODUCTION
1
PREFACE
PREFACE
FIGURES
TABLE OF
CONTENTS
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P R E FA C E
DRUG
IMPORTANCE
COST
FORECAST
TRENDS IN
EXPENDITURES
INTRODUCTION
PREFACE
DEAR READER,
Few industries enjoy the excitement and inherent value of the pharmaceutical industry — nor
do most sectors of the economy grow as rapidly. Prescription-drug development leads the way in
healthcare today — both in innovation and in cost increases.
This year’s Drug Trend Report analyzes the complex dynamics producing the continuing increase
in prescription drug costs. The factors driving trend — price inflation, the changing mix of
drugs taken, units per prescription, increased usage and new therapies — remain the same.
In 2000, drug trend increased at a rate of 16.2 percent, slightly lower than in 1999; 2000 was
the first time this has decreased since Express Scripts began measuring drug trend.
The continued escalation of drug costs is leading plan sponsors to adopt three-tier copay plans
and to evaluate other cost-management approaches such as defined-contribution benefits —
multiple-plan offerings that require members to choose among several drug plans with different
levels of coverage and corresponding member contributions.
Perhaps most importantly, this year’s Drug Trend Report adds a new chapter discussing the
relationship between drug costs and medical costs — both in the aggregate and for selected
chronic conditions. Whether increased drug costs are associated with decreased medical costs
is a hotly debated topic. Express Scripts’ data suggest that drugs may replace the costs of
selected medical services in certain circumstances. However, these data also indicate that,
for a variety of reasons, it is difficult to adequately measure the impact that prescription
drugs has on other medical costs.
We see improved patient care as the primary value of higher drug expenses — and it is to this
value that Express Scripts will direct future research. Faced with high drug and medical expenses,
plan sponsors (HMOs, employers and insurance carriers) must determine how they assess the
benefits versus the costs of different drug classes and decide whether this value is adequately
reflected in their plan designs.
Barrett A. Toan
Chairman and Chief Executive Officer
APPENDIX B
APPENDIX A
ACTIONS
Sincerely,
VI
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
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INTRODUCTION
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TABLE OF
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INTRODUCTION
BACKGROUND
NATIONAL HEALTH EXPENDITURES AS A PERCENT OF GDP AND PERCENT OF POPULATION 65 AND OLDER
15.9%
15.7%
15.5%
15.3%
15.1%
14.9%
14.6%
14.3%
13.9%
13.4%
13.1%
13.0%
13.0%
13.2%
13.3%
12.0%
8.8%
10
Percentage of US Population
Age 65 and Older
COST
FORECAST
15
13.4%
National Health Expenditures
as a percentage of GDP
%
20
DRUG
IMPORTANCE
5
0
TRENDS IN
EXPENDITURES
FIGURE 1
INTRODUCTION
Healthcare expenditures in general, and spending on prescription drugs in particular, have grown
significantly in recent years. Between 1980 and 1990, national health expenditures as a percentage
of Gross Domestic Product (GDP) grew by almost three-fourths from 8.8 percent to 12 percent
(see Figure 1). It is estimated that this share grew to 13.1 percent in 2000 and is projected to
rise to 15.9 percent in 2010. The magnitude of these increases has outstripped the aging of the
population, indicating that rising healthcare expenditures are attributable to more than simply
the graying of America.
PREFACE
Election politics brought heightened attention to the conundrum of high and ever-increasing
prescription drug costs. On one hand, prescription drugs are playing a more critical role in
disease treatment, a trend that will be discussed in more detail later in this report. On the other
hand, the costs of prescription drugs have outpaced the ability of many uninsured people, primarily
the elderly, to pay for their medications, and, indeed, the capacity of many companies to shoulder
the growing costs of health insurance premiums.
1980 1990 1993 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010
Source: Health Care Financing Administration1, U.S. Census Bureau2
ACTIONS
APPENDIX B
1
APPENDIX A
1 Health Care Financing Administration, Office of the Actuary: National Health Statistics Group; U.S. Department of
Commerce, Bureau of Economic Analysis. Table1: National Health Expenditures and Selected Economic Indicators, Levels
and Annual Percent of Change: Selected Calendar Years 1980-2010. National Health Care Expenditures Projections Tables.
Published March 2000, www.hcfa.gov/stats/NHE-Proj/proj2000/tables/t1.htm. Accessed March, 2001.
2 U.S. Census Bureau. 1900-1980,1980 Census of Population, General Population Characteristics, United States Summary
(PC80-1- B1); 1990, 1990 Census of Population, General Population Characteristics, United States Summary (CP-1-1); and
2000-2050, Population Projections of the United States by Age, Sex, Race, Hispanic Origin, and Nativity: 1999 to 2100.
Published January 2000, www.census.gov/population/www/projections/natproj.html Accessed March, 2001.
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PREFACE
As shown in Figure 2, since 1993-1994, the annual rate of increase in prescription drug
expenditures exceeded the growth rate of overall health expenditures. By 1997-1998, the annual
rate of increase in prescription drug expenditures grew 179 percent faster than overall health
expenditures and between 1998 and 1999 by 202 percent faster. HCFA actuaries project that the
annual rise in prescription drug costs will peak at 17.4 percent in 2000 before the rate of growth
gradually declines to 10.3 percent in 2010. In contrast, the annual growth rate in total national
health expenditures is expected to peak at 8.6 percent in 2001 and gradually decline to a 6.4 percent growth rate in 2010.
AVERAGE ANNUAL PERCENTAGE GROWTH FROM PREVIOUS YEAR
National Health Expenditures
%
Prescription Drugs
18
14
12
10
8
TRENDS IN
EXPENDITURES
TRENDS IN
EXPENDITURES
16
INTRODUCTION
FIGURE 2
As the cost pressures from rising drug costs mount, reliance on prescription drugs as an important treatment modality has grown. This inherent conflict is being played out against the hope
that drug spending will at least offset spending for other medical services. The extant literature
supports this proposition only in isolated instances such as treatment for diabetes11 and in some
cases for mental illness.12 Prescription drugs do oftentimes replace other more expensive forms of
therapies. For example, general risk factors for heart disease and stroke are well known, with
family history, obesity, high blood pressure, high cholesterol levels, diabetes and smoking at the
head of the list. Types of people who are at risk are fairly easy to identify. What remains unknown,
however, is which specific individuals, with or without identified risk factors, will have heart
attacks if they do not take medicines. Inpatient hospital costs are avoided only to the extent that
heart attacks and strokes are avoided. Since it is unknown which specific people will have heart
attacks without drug treatment, the money spent to provide these drugs to a large at-risk group
can easily be greater than the hospital costs that are saved for the few people that do avoid hospitalization for heart attacks. Thus, as this example demonstrates, it is probably more accurate to
assume that many prescription drugs save the lives of individual people, improve the quality of
life for those with a wide variety of illnesses and are a prerequisite for those who are interested in
promoting good quality of care. The key issue is who — the individual, the employer or the public
sector — should pay for what proportion of the cost of what types of pharmaceuticals.
PREFACE
INTRODUCTION
TABLE OF
CONTENTS
TABLE OF
CONTENTS
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SUMMARY OF FINDINGS
2
0
1960
1970
1980
1988
1990
1991
1992
1993
1994
1995
1996
1997
1998
ACTIONS
APPENDIX A
APPENDIX B
3
APPENDIX B
2 EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
3 Fifth Annual Survey on Purchasing Values in Health Care as cited in Managed Healthcare News, 2001; 17(2):11.
4 Goozner M. Drug makers, employers in battle over rising costs. Chicago Tribune Internet Edition 2000 , May 13 , 2000.
5 For 2001 Hewitt [and Associates]… is projecting average [healthcare cost] increases of 10% – 13%” as cited in Drug
Benefit Trends, December.
6 Credit Suisse First Boston Corporation, Employee Benefit Manager Survey 2000, January 30, 2001.
7 Noonan D. “GM’s war on drug costs. Newsweek; February 26, 2001:46-47.
8 Buck Consultants. Fifth Annual National Health Care Trend Survey. by Buck Consultants as cited by Reuters Health,
September 7, 2000.
9 The Segal Company. 2001 Segal Health Plan Cost Trend Survey. Published October 2000. abstract at
www.segalco.com/corporate/pub-corporate.cfm?ID=302 Accessed February, 2001.
10 William M. Mercer, Inc. Survey as cited in: Brubaker B. Steep rise predicted in health benefit costs. Washington Post
Online, Published December 12, 2000. Accessed February, 2001.
11 Testa MA, Simonson DC. Health economic benefits and quality of life during improved glycemic control in patients with
type 2 diabetes mellitus: a randomized, controlled, double-blind trial. Journal of the American Medical Association. 1998;
280(17):1490-1496.
12 Nightengale BS, Crumly JM, Liao J, Lawrence BJ, Jacobs EW. Economic outcomes of antipsychotic agents in a Medicaid
population: traditional agents vs Risperdal. Psychopharmacology Bulletin. 1998; 34(3): 373-382.
APPENDIX A
The private sector also is attempting to deal with spiraling drug costs. But unlike the public sector
that is discussing ways to subsidize drug costs, the private sector is faced with the dilemma of
how to continue paying for escalating healthcare costs — driven primarily by higher drug costs —
as the economy slows down and cost pressures grow. A variety of consultants and employer
surveys have documented that healthcare premiums rose more rapidly in the last two years than in
the recent past and that the dramatic increase in drug costs is a central reason for this phenomenon.3,4,5,6,7,8,9,10 To date, most employers have been willing to pay for all or most of these increases to
attract and retain employees in a tight labor market. However, as the economy slows, more employers are beginning to shift some of the burden of these cost increases to the employees.
Between 1996 and 2000
• Per Member Per Year (PMPY) Average Wholesale Price (AWP) ingredient costs grew by 85 percent.
• Drugs introduced since 1996 represent 35.7 percent of this growth.
ACTIONS
The impact of these dramatic increases in prescription drug costs on the elderly was manifested
during the 2000 election season. Presidential and Congressional candidates from both parties
talked about the plight of the elderly who cannot afford to pay for their medications. Some candidates escorted their elderly constituents to Canada and Mexico where prescription drugs are less
expensive. During the next year or two, the administration and Congress will debate various forms
that potential Medicare prescription coverage may take; governors and state legislators will
discuss how state government might help the uninsured pay for prescription drugs.
DRUG
IMPORTANCE
DRUG
IMPORTANCE
Source: Healthcare Financing Administration
The intent of the Express Scripts’ Drug Trend Report series is to provide clients with a better
understanding of the dynamics underlying current drug cost increases and future drug cost
trends. This fifth edition of the Express Scripts’ Drug Trend Report discusses the magnitude of
and the reasons for prescription drug cost increases between 1996 and 2000, with particular
emphasis placed on the 1999-2000 trend. Among the key findings of this study are:
COST
FORECAST
COST
FORECAST
4
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PREFACE
INTRODUCTION
TRENDS IN
EXPENDITURES
COST
FORECAST
DRUG
IMPORTANCE
Appendix B presents gender and age group profiles of prescription use across key therapy
classes. This information offers clients a way to better understand drug usage according to
the demographic makeup of their populations.
METHODS
APPENDIX A
APPENDIX A
4 EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
5
APPENDIX B
APPENDIX B
ACTIONS
The analyses contained in the 2000 Drug Trend Report are based on claims for prescription
medications for a substantial sample of Express Scripts clients. Prescriptions in this database
represent drug usage for a monthly average of 9.6 million members in 1999 and 8.8 million
members in 2000. Because of the unique demographics and drug coverage for Medicaid recipients
and Medicare beneficiaries receiving drug coverage through Medicare Plus Choice plans, data
from those two groups are excluded from this study. The resulting 2000 sample consists of 75
percent non-managed care commercial members and 25 percent managed care commercial
members. The average age of the sample population is 32.8, slightly higher than the 1999
sample age of 32.4. Drugs sold over-the-counter and prescriptions dispensed in inpatient settings
are also excluded from consideration. To ensure comparability across time periods and across
client groups, all cost figures are expressed as Average Wholesale Price (AWP) ingredient costs
(retail “list” price of the medication). Consequently, retail network discounts, mail discounts,
dispensing fees and member financial contributions are not reflected in these data. Overall
figures may not represent actual client experience due to differences in plan design. Finally,
the numbers of prescriptions dispensed through mail service have been converted to equivalent
numbers that would have been dispensed through retail pharmacies to adjust for differential
mail usage rates across Express Scripts clients.
DRUG
IMPORTANCE
The trend figures cited above reflect past experience with and future expectations about the
magnitude of drug cost increases on an AWP ingredient cost basis. When considered from a net
cost perspective — costs after discounts and member financial contribution — plan sponsors
can significantly curb costs. Plan sponsors that took aggressive steps saw their drug cost trend
decrease by one-half or more of the 2000 PMPY AWP trend.
Appendix A includes an analysis of drug cost changes across and within therapy classes between
1996 and 2000. This appendix highlights some of the key changes in utilization of specific drugs
and drug classes, as well as pointing out factors that are likely to impact future product mix in
these classes.
COST
FORECAST
These estimates are slightly lower than those presented in last year’s Report, despite the higher
inflation assumptions used in this edition. One major reason for this decline is the anticipated
decrease in the rates of cost increases in drug classes used for treatment of gastrointestinal
disorders, hyperlipidemia, pain/inflammation and diabetes. Some of the expected moderation
in utilization stems from a presumed increase in member financial contribution. As member
contribution goes up, utilization drops somewhat due to high out-of-pocket expenses.
Two appendices are included in this report.
TRENDS IN
EXPENDITURES
2001 Through 2005 Projections
PMPY AWP ingredient costs are projected to increase by:
• 15.4 percent in 2001
• 12.7 percent in 2002
• 11.9 percent in 2003
• 11.6 percent in 2004
• 11.3 percent in 2005
The first portion of this Report describes the reasons for the 1999-2000 drug cost growth, followed
by our PMPY AWP drug cost forecast for the period from 2001-2005. This section includes an
analysis of pipeline drugs that may come to market during this period, as well as drugs that will
lose patent protection and become eligible to become generics. The next section of this Report
describes the role of prescription drugs in the healthcare treatment arsenal. This new section
explores the magnitude of and the change in the relative proportion of overall healthcare spending
that was attributable to prescription drugs between 1999 and 2000. The final part of this analysis
discusses the types of actions that plan sponsors can take to offset growing prescription costs.
INTRODUCTION
Between 1999 and 2000
• In 2000, PMPY AWP ingredient costs grew by 16.2 percent, from $387.09 in 1999 to $449.74.
This is the first time since Express Scripts began monitoring prescription drug trends in 1993
that the rate at which PMPY AWP costs rose slowed from the previous year.
• The PMPY AWP growth rates for non-managed care clients grew at a somewhat lower rate of
14.9 percent.
• About three-fourths of this increase is attributable to increased costs per prescription, although
this percentage varies across therapy classes.
• The inflation rate for common drugs (drugs available in 1999 and 2000) grew by 5.4 percent,
the third consecutive year that inflation topped 5 percent. Inflation accounted for one-third of
the overall 1999-2000 drug expenditure increase.
• Increased use of non-steroidal anti-inflammatory drugs, gastrointestinal products, antihyperlipidemics and antidepressants accounted for $25.08, or 40 percent, of the total $62.65
cost increase.
PREFACE
ACTIONS
TABLE OF
CONTENTS
TABLE OF
CONTENTS
22501_ii58
APPENDIX B
APPENDIX A
ACTIONS
DRUG
IMPORTANCE
COST
FORECAST
TRENDS IN
EXPENDITURES
INTRODUCTION
PREFACE
TABLE OF
CONTENTS
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TABLE OF
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TRENDS IN EXPENDITURES FOR PRESCRIPTION DRUGS
PREFACE
Express Scripts began monitoring prescription drug costs for the 1993-1994 period. Every year
from 1993 through 1999, PMPY AWP costs have increased at a faster pace than in the previous
year. In 2000, however, while still growing by 16.2 percent, PMPY AWP ingredient costs grew less
than the 17.4 percent these costs rose in 1999. PMPY AWP ingredient costs grew to $449.74 —
$62.65 over 1999 PMPY costs, representing an 85 percent rise over the 1996 PMPY cost of
$243.34 (see Figure 3).
INTRODUCTION
FIGURE 3
PER MEMBER PER YEAR AWP COSTS 1996-2000
$500
449.74
$450
387.09
$400
329.83
$350
TRENDS IN
EXPENDITURES
$300
282.48
234.34
$250
$200
$150
$100
$50
1996
1997
1998
1999
2000
TABLE 1:
ACTIONS
To understand the dynamics underlying these cost trends, growth rates for one-year and five-year
periods were analyzed in terms of 1) changes in the utilization of medications — so-called common
drugs — that were available for use between 1996 and 2000; 2) increases in AWP ingredient costs
per prescription of these common drugs; and 3) introduction of new products to the market.
DRUG
IMPORTANCE
Managed care clients experienced slightly higher PMPY cost increases (16.2 percent) than nonmanaged care clients (14.9 percent). This disparity is due primarily to higher rates of increase
in therapeutic mix and in the number of units per prescription among managed care clients. The
actual net claim costs trend for Express Scripts’ clients ranged from zero to a 35 percent rise,
depending on how aggressively plan sponsors chose to implement Express Scripts’ recommended
cost-management programs.
COST
FORECAST
$0
COMPONENTS OF PER MEMBER PER YEAR COST TREND 1996-2000*
1996 v 1997
1997 v 1998
1998 v 1999
1999 v 2000
1996 v 2000
2.4%
1.0%
0.6%
4.7%
4.5%
13.7%
2.4%
5.1%
0.6%
0.6%
4.4%
3.8%
15.2%
1.6%
5.4%
0.2%
0.8%
2.3%
6.2%
15.6%
1.8%
5.4%
1.0%
0.9%
4.2%
3.7%
15.9%
0.3%
20.3%
2.7%
4.2%
9.9%
10.2%
54.0%
31.0%
= All Drug
16.1%
16.8%
17.4%
16.2%
85.0%
7
APPENDIX B
*The percentage contribution of each factor does not total to the All Drug percentage increase.The calculation takes the base cost for a
given year and multiplies it by one times the percentage contributed by the first factor (pricing). The resulting total is then multiplied by
the percentage contributed by the second factor (number of units dispensed), and so on. The percentage contribution of the New Drugs
is then added to the total Common Drug percentage to yield an All Drug percentage increase. The final results may differ due to rounding.
APPENDIX A
Inflation
Units per Rx
New Strengths
Mix
Utilization
= Common Drugs
+ New Drugs
6/4/01
2:58 PM
Page 8
PREFACE
Between 1996 and 2000, PMPY AWP ingredient costs grew by 85 percent from $243.34 to
$449.74. Almost $98 of the total $206.40 increase is attributable to the rise in per prescription
costs. Inflation alone accounted for about $48 of the overall increase and an additional $30
is attributable to therapeutic mix. Utilization of common drugs contributed about $34 of the
increase, while drugs introduced since 1996 accounted for approximately $74 of the 1996-2000
cost growth rate.
CHANGES IN COMMON DRUG COSTS BETWEEN 1999 AND 2000
COST
FORECAST
DRUG
IMPORTANCE
ACTIONS
Total
8.28
8.57
3.6%
While ranking only 22nd in terms of common drug use at 0.12 prescriptions PMPY, the use rate
increase of 12.5 percent placed anticonvulsants as the second-fastest growing class. This large
rise in use was fueled by wider use of Neurontin®, which is prescribed more and more as a pain
control medication. The market share for Neurontin® grew from 17.1 percent in 1999
to 21.6 percent in 2000.
The use of common drugs in the non-steroidal anti-inflammatory (NSAID) class rose 12 percent
in 2000 to 0.34 PMPY. This substantial increase was due primarily to the dramatic growth in
prescriptions written for cyclo-oxygenase 2 (COX-2) inhibitors, Celebrex® and Vioxx®. Introduced
in 1999, the combined market share for these products grew from 18.9 percent in 1999 to
39.8 percent in 2000. It is anticipated that sales of these products will continue to grow, in
part because of the DTC advertising for these products. In the first nine months of 2000,
about $193 million was spent on DTC advertising for Celebrex® and Vioxx®.14
14 Ibid.
9
APPENDIX B
8 EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
9.5%
9.9%
9.7%
-2.6%
17.0%
7.5%
12.0%
-9.8%
7.1%
0.6%
-5.1%
-3.5%
6.9%
0.8%
8.1%
5.4%
-1.9%
5.7%
5.9%
-7.4%
-11.3%
-1.4%
12.5%
1.1%
-1.3%
3.6%
3.4%
APPENDIX A
13 Scott-Levin. Direct-to-Consumer Advertising Audit and Competitive Media Reporting. Third Quarter 2000.
0.56
0.51
0.41
0.41
0.37
0.35
0.34
0.33
0.31
0.29
0.29
0.28
0.27
0.27
0.26
0.26
0.25
0.22
0.19
0.19
0.14
0.13
0.12
0.11
0.10
6.98
1.60
ACTIONS
Similar to past years, changes in utilization of common drugs between 1999 and 2000 varied
widely (see Table 2). In 2000, utilization of common drugs declined in nine of the top 25 therapy
classes, compared to only three in 1999. In contrast, only three therapeutic classes experienced
double-digit utilization growth in 2000. The use of common antihyperlipidemic medicines rose
by 17 percent, catapulting this class to the fastest growing class in terms of utilization in 2000.
This significant growth rate took place on top of the 16.3 percent and 18.1 percent rates in 1998
and 1999 when antihyperlipidemics ranked as the second fastest rising class next to antihistamines.
Indeed by 2000, a PMPY use rate of 0.37 placed antihyperlipidemics as the fifth most used drug
class. These dramatic increases in the use of antihyperlipidemics in recent years have been
spurred not only by evidence showing that their use reduces mortality but also by substantial
direct-to-consumer (DTC) advertising. According to Scott-Levin’s Direct-to-Consumer Advertising
Audit and Competitive Media Reporting, $130.4 million was spent on DTC advertising for these
products just between January and September 2000.13 Lipitor® dominated this class with a
51.8 percent market share, followed by Zocor® and Pravachol® with 2000 market shares that
declined to 15.7 percent and 13.8 percent, respectively.
0.51
0.46
0.38
0.42
0.32
0.32
0.30
0.37
0.29
0.29
0.30
0.29
0.26
0.27
0.24
0.25
0.25
0.21
0.18
0.20
0.15
0.14
0.11
0.11
0.10
6.73
1.54
% Change
DRUG
IMPORTANCE
APPENDIX A
After growing by a robust 6.3 percent between 1998 and 1999, the rate of increase in the utilization
of common drugs slowed to 3.6 percent, the lowest rate of increase seen since the 1995-1996
timeframe. In turn, utilization of common drugs accounted for 25.6 percent of the overall 19992000 PMPY growth. In contrast, utilization of common drugs represented 38.8 percent of the
1998-1999 total cost rise. Despite the slower growth rate, PMPY utilization reached 8.57 in
2000 compared to 8.28 in 1999.
Antihypertensives
Antidepressants
Narcotic Analgesics
Estrogens
Antihyperlipidemics
Gastrointestinals
Anti-Rheumatics (NSAIDS)
Cough/Cold
Antidiabetics
Antiasthmatics
Penicillins
Oral Contraceptives
Antihistamines
Dermatologicals
Beta Blockers
Diuretics
Calcium Blockers
Thyroid
Antianxiety Agents
Macrolides
Cephalosporins
Decongestants
Anticonvulsants
Ophthalmic Products
Corticosteroids
Top 25
Other
Therapy Class
COST
FORECAST
APPENDIX B
To determine the nature of variable use patterns across therapeutic drug groupings, common
drugs were categorized into therapy classes — groups of pharmaceutical agents that are chemically or therapeutically related. Products were grouped according to the first two digits of the
14-digit Generic Product Identifier (GPI) code as classified by First DataBank. This classification
system defines broad drug groups employed to treat similar medical conditions. This classification
scheme is used in the remainder of this Report.
2000
Selected Year
Rxs PMPY
TRENDS IN
EXPENDITURES
TRENDS IN
EXPENDITURES
Utilization of Common Drugs
1999
Previous Year
Rxs PMPY
INTRODUCTION
The following sections discuss in more detail how each of the components of cost trend contributed
to cost increases of the combined non-managed and managed commercial memberships between
1999 and 2000.
TABLE 2:
UTILIZATION OF COMMON DRUGS OF TOP 25 THERAPY CLASSES 1999-2000
RANKED BY 2000 PRESCRIPTIONS PER MEMBER PER YEAR
PREFACE
INTRODUCTION
TABLE OF
CONTENTS
TABLE OF
CONTENTS
22501_ii58
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Page 10
10 EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
16 Ibid.
11
APPENDIX B
15 Ibid.
APPENDIX A
From 1997 through 1999, antihistamines experienced the largest percentage utilization increases
of any class. In 2000, the rise in antihistamine use was 6.9 percent, making it the 10th highest
The use of common antiasthmatic drugs remained flat at 0.29 prescriptions PMPY. The continued
relatively stable use of this drug class is somewhat surprising given the emphasis that has been
placed on asthma control in recent years and the central role that prescription drug therapy plays
in that control.
ACTIONS
The use of common antidiabetic drugs increased by 7.1 percent to 0.31 PMPY in 2000. The
continued rise in the use of this class is attributable to the emphasis on aggressive management
of diabetes, as well as to the availability of newer oral products such as Glucophage®, which
increased its market share from 21.5 percent in 1998 to 28 percent in 2000.
After growing by 13.2 percent in 1999, the use of drugs in the macrolide antibiotic class decreased
by 7.4 percent to 0.19 prescriptions PMPY in 2000. With the growing problem of bacterial resistance,
especially S. pneumoniae, many physicians are initiating therapy with narrower spectrum antibiotics,
as evidenced by the 5.1 percent decrease in PMPY utilization of penicillins and the 11.3 percent
decline in the use of cephalosporins.
PREFACE
INTRODUCTION
TRENDS IN
EXPENDITURES
COST
FORECAST
DRUG
IMPORTANCE
DRUG
IMPORTANCE
In 2000, the use of GI drugs rose by 7.5 percent to 0.35 prescriptions PMPY. The continued
significant increase seen in the utilization of GI drugs over the past several years was partially
the result of greater use of proton pump inhibitors (PPIs), Prilosec®, Prevacid® and Protonix®.
Manufacturers of these products have effectively used DTC advertising to help increase their
combined market share from 36.2 percent in 1997 to 60 percent in 2000. From January through
September of 2000, $124 million was spent for DTC advertising of PPIs.15
The PMPY use of cough and cold products and common decongestants declined in 2000. PMPY
utilization of the cough/cold class decreased by almost 10 percent to 0.33 prescriptions PMPY.
This follows a 12.9 percent rise in the use of these products in 1999. Generics still hold a majority
market share, 54.9 percent, but they are losing ground to Claritin® D and Allegra® D. Utilization of
common decongestants, consisting primarily of nasal steroids used to alleviate allergy symptoms,
declined by 1.4 percent to 0.13 prescriptions PMPY. Flonase® and Nasonex® continue to dominate
this market with a combined market share of 55.5 percent.
COST
FORECAST
Consisting of angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers
(ARBs), vasodilators and combination products, the antihypertensive class continues to be the
most widely prescribed therapy class. In 2000, the use of antihypertensives grew by 9.5 percent
to 0.56 prescriptions PMPY. This strong growth pattern will likely continue as the population
ages. Most heavily prescribed in this class were the ACEIs. Both new indications for use of ACEIs
and the perception that ACEIs have superior efficacy and better side effect profiles than other
kinds of cardiac medications have added to their increasing popularity. Changes in the 2000
PMPY use of other cardiac-related drug classes were mixed. The use of beta blockers and diuretics,
the recommended first-line agents for uncomplicated hypertension, grew by 8.1 percent and
5.4 percent, respectively. In contrast, the use of calcium blockers continued to decline, dropping
by 1.7 percent.
Between 1999 and 2000, changes in utilization of common drugs in several drug classes pertaining
to women’s health were mixed. Increases were seen in the use of thyroid replacement products
and miscellaneous endocrine agents in 2000, but declines were evident in use of estrogens and
oral contraceptives. PMPY utilization of thyroid replacement products rose by 5.7 percent, slightly
below its 8.3 percent rise in 1999. Although the PMPY use of miscellaneous endocrine agents
stands at 0.06 PMPY, its use increased by more than 30 percent. This growth was fueled by the
increased use of Fosamax® and Evista®, products that dominate the miscellaneous endocrine
class with a combined 72.6 percent market share. The use of these products, in conjunction with
possible negative side effects related to estrogen use, contributed to the 2.6 percent decline in
the utilization of estrogens, commonly used to treat postmenopausal symptoms and to prevent
osteoporosis. Because of this decrease in use, estrogens dropped from the third to the fourth most
widely prescribed class of drugs at 0.41 prescriptions PMPY. After growing during 1999, utilization
of oral contraceptives declined by 3.5 percent to 0.28 prescriptions PMPY in 2000. This decrease
likely is related to changes in plan design regarding coverage of oral contraceptives.
TRENDS IN
EXPENDITURES
ACTIONS
In 2000, the use of narcotic analgesics grew by 9.7 percent, or 1.7 times the overall increase in
common drugs. The 2000 common drug use rate of 0.41 PMPY moved narcotic analgesics from
the fourth to the third most widely used class of drugs. The increased use of these medications is
due to several factors that include more-aggressive pain management strategies — particularly
for non-life threatening conditions such as lower back pain — the growing number of patients
being treated in outpatient settings and longer survival times for more terminally ill patients.
rising class in terms of common drug utilization. At 0.27 prescriptions PMPY, antihistamines
maintained position as the 13th most used therapy class. The continued widespread use of
antihistamines is manifest in the use of three non/low sedating products, Claritin®, Allegra®
and Zyrtec®, that account for nine out of every 10 prescriptions written for antihistamines.
More money, $197 million, was spent on DTC advertising for antihistamine products than for
any other class of drugs during the first nine months of 2000.16
INTRODUCTION
APPENDIX A
PMPY utilization of common antidepressant drugs increased by 9.9 percent to 0.51 PMPY in 2000.
The antidepressant class was the fourth fastest growing in terms of common drug use, maintaining its status as the second most-used class of common drugs in 2000. Part of this increase is
due to the use of these products for new indications such as social phobia, bulimia nervosa, post
traumatic stress disorder and generalized anxiety disorder. This class continues to be dominated
by selective serotonin reuptake inhibitors (SSRIs), such as Prozac®, Zoloft®, Paxil® and Celexa®,
and by selective norepinephrine reuptake inhibitors (SNRIs), such as Effexor®.
PREFACE
APPENDIX B
TABLE OF
CONTENTS
TABLE OF
CONTENTS
22501_ii58
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Page 12
AWP INGREDIENT COST PER PRESCRIPTION
INFLATION
Almost three-quarters of the overall PMPY drug cost increase between 1999 and 2000 is attributable to the rise in AWP ingredient costs per prescription for common drugs. In contrast, growth in
per prescription costs represented one-half of the overall 1998-1999 PMPY cost increase.
Components of the trend in the cost per prescription for common drugs are:
Inflation reflects the AWP that manufacturers set for each unit of their product. Between 1999
and 2000, inflation grew 5.4 percent. This marks the third consecutive year that inflation has
topped 5 percent. By comparison, inflation ranged from 1 percent to 3.3 percent between 1993
and 1997. Based on Consumer Price Index (CPI) statistics reported by the U.S. Department of
Labor (which defines inflation somewhat differently than this analysis), the inflation rate for
prescription drugs has continued to exceed the rate of increase for the overall CPI, as well as
for other types of medical care.17 This trend has occurred in each of the last three years.
Therapeutic mix (changes in the mix of chemical entities within and across therapeutic classes)
Strength mix (changes in the mix of strengths and dosage forms of existing chemical entities)
COST
FORECAST
FIGURE 4
Inflation 45.0%
Therapeutic Mix 37.9%
Units 8.7%
APPENDIX A
APPENDIX A
ACTIONS
ACTIONS
Strength Mix 8.4%
DRUG
IMPORTANCE
DRUG
IMPORTANCE
PERCENT OF AWP CHANGE ATTRIBUTED TO INFLATION, UNITS,
THERAPEUTIC MIX AND STRENGTH MIX 1999-2000
Across the top 25 classes, generics also had a greater variation in trend rates with nine classes
having inflation rates of greater than 10 percent and nine classes with rates under 4 percent
(see Table 3). In contrast, among brands, only two classes had trend rates above 10 percent
and two classes fell below 4 percent. Among the generic classes with high inflation rates, this
inconsistency is likely due to the aggressive pricing strategies of selected generic manufacturers
operating in the generic market where the scrutiny of AWP price changes is not as great as it
is with brands. Conversely, the classes with low generic trend may be a reflection of backlash
generated from pricing strategies that were too aggressive. A case in point was the lawsuit
charging unfair pricing practices that was filed two years ago against the makers of generic
antianxiety drugs.
COST
FORECAST
Inflation, the number of units dispensed and the two types of mix contributed somewhat unevenly
to the 1999-2000 change in per prescription cost. (See Table 1 and Figure 4) While there are variations across therapy classes, generally between 1999 and 2000 for common drugs, inflation had
by far the greatest impact on the average AWP ingredient cost per prescription, followed by therapeutic mix, number of units per prescription and strength mix. The relative contributions of these
factors to the overall increase in the average prescription AWP cost for common drugs are
described below.
TRENDS IN
EXPENDITURES
TRENDS IN
EXPENDITURES
Units (the number of units dispensed per prescription)
In the 1999-2000 time period inflation was the largest cost trend driver, accounting for one-third
of the total cost increase. Because inflation rates did not increase in a uniform manner, inflation
must be examined between brands and generics as well as across therapy classes. The data indicate that generics, at 7.1 percent, experienced a higher inflation rate than brands, which grew by
5.4 percent. (The apparent anomaly of a 5.4 percent increase in brand prices and a 7.1 percent
increase in generic prices resulting in a 5.4 percent increase for all products reflects the fact that
our inflation rate also captures cost changes resulting from the shift from branded products to
their generic equivalents. The move to generics somewhat moderates the inflation rate because
generics are usually less expensive than their brand equivalents.) The respective inflation rates
are very close to the 7 percent and 5.8 percent seen for generics and brands in 1999.
INTRODUCTION
INTRODUCTION
Inflation (AWP price increases per unit moderated by the availability of less expensive generic
equivalents for branded products)
PREFACE
PREFACE
TABLE OF
CONTENTS
TABLE OF
CONTENTS
22501_ii58
12 EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
13
APPENDIX B
APPENDIX B
17 Bureau of Labor Statistics, U. S. Department of Labor. Consumer price index-all urban consumers (current series).
Updated January, 2001. http://146.142.4.24/labjava/outside.jsp?survey=cu Accessed January, 2001.
6/4/01
2:58 PM
Page 14
PREFACE
INTRODUCTION
TRENDS IN
EXPENDITURES
COST
FORECAST
Therapy Class
Thyroid
Estrogens
Corticosteroids
Dermatologicals
Antidiabetics
Diuretics
Cough/Cold
Beta Blockers
Penicillins
Antidepressants
Macrolides
Ophthalmic Products
Anticonvulsants
Narcotic Analgesics
Antihyperlipidemics
Anti-Rheumatics (NSAIDS)
Decongestants
Antianxiety Agents
Antihistamines
Cephalosporins
Gastrointestinals
Antihypertensives
Antiasthmatics
Oral Contraceptives
Calcium Blockers
Top 25
Other
Price % Change
Branded Products
Price % Change
All Products
22.7%
1.2%
12.1%
14.3%
16.1%
8.6%
13.7%
6.3%
0.8%
11.8%
2.8%
1.0%
6.1%
8.9%
10.9%
8.6%
-20.4%
3.1%
20.3%
2.1%
3.8%
10.0%
0.8%
7.8%
5.0%
6.9%
7.8%
11.8%
14.0%
8.0%
9.7%
5.9%
7.0%
5.4%
5.6%
7.4%
4.9%
5.5%
6.7%
5.3%
4.0%
4.8%
3.6%
4.8%
9.5%
4.5%
5.9%
4.4%
5.0%
5.5%
4.6%
3.7%
5.5%
4.9%
13.2%
12.6%
10.2%
9.9%
7.3%
7.1%
7.0%
6.2%
5.6%
5.3%
5.3%
5.2%
5.2%
5.1%
5.1%
5.1%
4.8%
4.8%
4.6%
4.6%
4.2%
4.2%
3.9%
3.8%
2.4%
5.4%
5.2%
7.1%
5.4%
5.4%
$1.97
$2.44
$4.00
$4.14
$6.76
$0.64
$1.02
$2.85
$1.11
$2.52
$3.05
$1.92
$2.62
$0.69
$3.50
$2.53
$2.34
$2.41
$1.03
$1.37
$0.38
$1.60
$0.90
$2.17
$0.62
$2.16
$2.75
$0.96
$1.38
$4.51
$2.43
$2.24
$1.03
$3.22
$0.61
$0.81
$11.89
$5.19
$1.16
$0.35
$8.53
$2.41
$3.76
$5.35
$3.98
$3.50
$0.54
$1.09
$1.12
$0.78
4.9%
8.8%
7.0%
3.9%
3.1%
12.8%
18.2%
7.9%
3.9%
4.0%
4.9%
3.1%
8.2%
6.9%
5.0%
8.7%
3.1%
3.1%
4.0%
3.1%
0.0%
5.0%
12.8%
0.0%
12.8%
7.1%
8.8%
4.0%
8.8%
8.7%
6.9%
4.9%
4.0%
7.0%
4.0%
4.9%
3.1%
9.1%
4.0%
12.1%
0.0%
5.1%
6.9%
4.0%
4.5%
0.0%
8.2%
6.9%
4.9%
12.8%
# of Price Changes
Between 12/31/1999
and 12/31/2000
1
3
2
1
1
2
2
3
1
1
1
1
2
1
1
2
1
1
1
1
0
1
2
0
2
2
4
1
4
2
1
1
1
2
1
1
1
2
1
2
0
1
1
1
1
0
2
2
1
2
15
APPENDIX B
14 EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
$1.88
$2.24
$3.73
$3.99
$6.55
$0.57
$0.87
$2.64
$1.07
$2.42
$2.90
$1.86
$2.42
$0.65
$3.34
$2.33
$2.27
$2.34
$0.99
$1.32
$0.38
$1.53
$0.79
$2.17
$0.55
$2.02
$2.53
$0.93
$1.26
$4.15
$2.27
$2.14
$0.99
$3.01
$0.58
$0.77
$11.53
$4.76
$1.11
$0.31
$8.53
$2.29
$3.52
$5.14
$3.81
$3.50
$0.50
$1.02
$1.07
$0.69
Percent
Change
APPENDIX A
Analysis of the thyroid class reveals that the price of the dominant brand, Synthroid®, increased
slightly more than 12 percent in 2000 (see Table 4). However, the brand increase alone was not
enough to propel the thyroid class to the top of the inflation list. Among generic products only,
thyroid medications were also at the top of the list with an inflation trend of 22.7 percent. Leading
the charge was the branded generic Levoxyl®. The price of the most commonly dispensed form of
Levoxyl® was increased three times in 2000 and ended the year at a unit cost almost 34 percent
higher than at the end of 1999.
LIPITOR® 10MG
CLARITIN® 10MG
PREVACID® 30MG
PRILOSEC® 20MG
ZITHROMAX® 250MG
PREMARIN® 0.625MG
PREMPRO® 0.625-2.5MG
PROZAC® 20MG
ORTHO TRI-CYCLEN®
CELEBREX® 200MG
LIPITOR® 20MG
ZYRTEC® 10MG
VIOXX® 25MG
GLUCOPHAGE® 500MG
FLONASE® 50MCG
PAXIL® 20MG
ZOLOFT® 50MG
ZOLOFT® 100MG
ALLEGRA® 60MG
NORVASC® 5MG
TRIMOX® 500MG
WELLBUTRIN SR® 150MG
PREMARIN® 1.25MG
NORVASC® 10MG
PREMARIN® 0.625MG
CELEXA® 20MG
CLARITIN-D 24 HOUR® 240-10MG
ZESTRIL® 10MG
CLARITIN-D 12 HOUR® 120-5MG
CIPRO® 500MG
PRAVACHOL® 20MG
AMBIEN® 10MG
ZESTRIL® 20MG
NASONEX® 50MCG
TOPROL XL® 50MG
ULTRAM® 50MG
DIFLUCAN® 150MG
AUGMENTIN® 875-125MG
ALLEGRA-D® 120-60MG
SYNTHROID® 100MCG
LEVAQUIN® 500MG
HUMULIN® N 100U/ML
BIAXIN® 500MG
SEREVENT® 21MCG
ZOCOR® 20MG
LIPITOR® 40MG
K-DUR® 20MEQ
TRIPHASIL-28®
ORTHO-NOVUM® 7-7-7
PREMARIN® 0.9MG
Unit Price on
12/31/2000
ACTIONS
The top two classes in terms of price increases are those that have been consistently at the top of
the list in the last several years: thyroid drugs and estrogens. The common denominator between
these two classes is that each is dominated by single brands made by one company, with relatively
little generic competition. This combination has allowed substantial price increases of the dominant
brands without fear of a loss of market share to competition. These price increases have been
masked in part by the fact that the most commonly dispensed drugs are relatively inexpensive.
While manufacturers can claim small per unit dollar increases, the percentage increases are
actually high.
Product
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
Unit Price on
12/31/1999
DRUG
IMPORTANCE
Total
Price % Change
Generic Products
COST
FORECAST
DRUG
IMPORTANCE
PRICE CHANGES FOR TOP 50 COMMON BRAND DRUGS 1999-2000
TRENDS IN
EXPENDITURES
ACTIONS
TABLE 4
INTRODUCTION
APPENDIX A
TABLE 3
PRICE CHANGES DUE TO INFLATION OF TOP 25 THERAPY CLASSES 1999-2000
RANKED BY PERCENT CHANGE IN PRICE
PREFACE
APPENDIX B
TABLE OF
CONTENTS
TABLE OF
CONTENTS
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Total
PREFACE
INTRODUCTION
TRENDS IN
EXPENDITURES
COST
FORECAST
DRUG
IMPORTANCE
Strength Mix
% Change
Total Mix
% Change
13.6%
10.7%
7.5%
4.5%
7.3%
5.1%
3.4%
5.1%
1.8%
2.8%
1.1%
0.4%
0.5%
1.3%
0.2%
-0.1%
0.1%
0.4%
-1.1%
-2.8%
-0.7%
-0.8%
0.5%
-1.2%
-3.3%
4.1%
4.7%
0.5%
2.7%
1.3%
3.6%
0.3%
2.2%
1.9%
0.0%
1.6%
0.4%
0.9%
1.1%
0.8%
-0.4%
0.4%
0.5%
0.1%
-0.4%
0.6%
2.3%
0.1%
0.1%
-1.2%
0.1%
0.5%
0.9%
0.6%
14.1%
13.4%
8.9%
8.1%
7.6%
7.3%
5.3%
5.0%
3.3%
3.2%
2.1%
1.5%
1.3%
1.0%
0.6%
0.5%
0.2%
0.1%
-0.5%
-0.6%
-0.6%
-0.6%
-0.7%
-1.0%
-2.7%
5.0%
5.3%
4.2%
0.9%
5.1%
17
APPENDIX B
16 EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
Anti-Rheumatics (NSAIDS)
Narcotic Analgesics
Anticonvulsants
Penicillins
Antiasthmatics
Antidiabetics
Cough/Cold
Ophthalmic Products
Antianxiety Agents
Gastrointestinals
Dermatologicals
Decongestants
Antidepressants
Estrogens
Antihypertensives
Calcium Blockers
Oral Contraceptives
Thyroid
Antihistamines
Antihyperlipidemics
Macrolides
Diuretics
Beta Blockers
Corticosteroids
Cephalosporins
Top 25
Other
Therapeutic Mix
% Change
APPENDIX A
Therapeutic mix is the use of relatively more expensive or less expensive drugs within and across
therapy classes. Strength mix refers to cost impacts caused by shifts to more or less expensive
strengths of the same drug or by the introduction of new strengths for existing products. In 2000,
the impact of therapeutic mix on overall trend was 4.2 percent, a dramatic increase over the
2.3 percent seen from 1998 to 1999 but more in line with trends seen from 1995 through 1998.
The impact of strength mix continued to climb to 0.9 percent. Although the impact of strength mix
is relatively small compared to therapeutic mix, it is still relevant because it reflects the tendency
of manufacturers to modify their existing drugs to improve patient compliance or to comply with
new treatment recommendations.
Therapy Class
ACTIONS
THERAPEUTIC MIX AND STRENGTH MIX
PRICE CHANGES DUE TO MIX OF TOP 25 THERAPY CLASSES 1999-2000
DRUG
IMPORTANCE
Antidiabetics rounded out the top five classes in inflation trend. While the brand inflation trend
in this class was a relatively modest 5.9 percent, just slightly higher than the overall class
average, the generic inflation trend shot up by 16.1 percent. Not coincidentally, the generic fill
rate decline in the antidiabetic class was among the largest of the top 25 classes. The market
share of generic sulfonylureas, traditionally the drugs of choice to treat Type 2 diabetes, is being
eroded by newer branded classes that work in different ways. In response to this loss in market
share, generic manufacturers apparently have increased prices in an attempt to maintain
consistent revenues.
TABLE 5
COST
FORECAST
Dermatologicals were another class for which the generic inflation rate outpaced the brand rate,
contributing to the overall trend. However, dermatologicals were ranked in the top four for both
brand and generic trend, in turn ranking the entire class fourth among the top 25. Among
branded dermatologicals, three products — Benzamycin®, Bactroban® and Accutane® —
experienced inflation trend of greater than 15 percent. These three products are all either off
patent (Benzamycin® and Bactroban®) or soon to go off patent (Accutane® in August 2001). In
each case the dramatic price increases may be a reflection of their manufacturers’ desire to
maximize revenues prior to the onset of generic competition. The primary reason for the large
increase in generic dermatologicals was the increase in the highest volume generic product.
The most frequently dispensed size/strength for desoximetasone cream, used to treat inflammation
and itch associated with several skin conditions, increased 35.9 percent.
TRENDS IN
EXPENDITURES
ACTIONS
The class with the third greatest inflation increase was oral corticosteroids. The ranking represented
a 14-position leap from last year. With greater than a 92 percent generic fill rate and an average
cost per prescription of less than $10, this class is similar to the thyroid products — generic
manufacturers can mask large percentage increases with small dollar increases.
As seen in Table 5, the therapeutic mix trend from 1999 to 2000 for the top 25 classes by utilization
was 4.1 percent. Between the trend periods 1998-1999 and 1999-2000 the top five mix trend
classes — anti-rheumatics, narcotic analgesics, anticonvulsants, penicillins and antiasthmatics
— remained the same, although ranked in a different order. Between 1999 and 2000, antirheumatics and narcotic analgesics were far and away the leading classes in this trend component at 14.1 percent and 13.4 percent combined mix, respectively. Within the anti-rheumatic class,
the COX-2 products, Celebrex® and Vioxx®, more than doubled their combined market share from
18.9 percent in 1999 to 39.8 percent in 2000. However, despite the resulting significant blow to
the market share of branded NSAIDS, the dramatic increase in mix trend is due primarily to the
erosion of the cheaper generic NSAID market share by more expensive COX-2 brands. To a lesser
extent the increase in market share of DMARDs, Arava® and Enbrel® has also increased mix trend.
These were the only others in the top 20 anti-rheumatics to gain market share. Their high costs
relative to the class average (Arava® is 3.5 times the class average and Enbrel® 15 times the
class average) show why these products can significantly impact mix trend with only small
increases in market share.
INTRODUCTION
APPENDIX A
The combination of a 14 percent brand increase and a low 12 percent generic fill rate resulted
in a 12.6 percent inflation increase for the estrogen class. As in years past, the manufacturer of
Premarin® made two price increases in 2000 to end the year at a unit cost almost 13 percent
higher than the price at the end of 1999. The AWP of Prempro®, a combination conjugated estrogen
and progestin product, which has been gaining market share in recent years, only changed twice
during 2000 but still experienced an 18.2 percent jump. This rise was twice the rate of increase
of any other drug among the top 50 brands, except for Premarin® and Synthroid®.
PREFACE
APPENDIX B
TABLE OF
CONTENTS
TABLE OF
CONTENTS
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APPENDIX A
PREFACE
INTRODUCTION
TRENDS IN
EXPENDITURES
COST
FORECAST
APPENDIX A
ACTIONS
18 EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
19
APPENDIX B
APPENDIX B
DRUG
IMPORTANCE
The last of the top five mix trend classes, antiasthmatics, experienced results similar to
what occurred in 1999. Asthma controllers Singulair® tablets and Flovent® inhalers experienced
4 percent and 3.3 percent market share gains, respectively. This reflects the practice among
people with asthma to use products that control the condition rather than products that stop
asthma attacks once they have started. Other products worth mentioning because of their
impact on mix trend are Pulmicort®, RespulesTM and Serevent®. Pulmicort® RespulesTM, an
inhaled steroid in a new dosage form for children as young as one year old, was a mix trend
factor because of its relatively high cost. Serevent®, and in particular the Serevent® Diskus
inhalation powder product, was a factor in 2000 and is likely to be a factor in future years
as CFC-free products gain popularity.
The ophthalmic class mix trend was almost entirely due to a 5.1 percent increase in therapeutic
mix. This increase was slightly over 1 percent greater than last year. The biggest movers in this
class were Xalatan®, used to treat glaucoma, and Patanol®, used to treat eye irritation caused by
allergies. These two products increased market share by 1.4 percent and 1.2 percent, respectively.
The market share increase for Xalatan® was greater in 1999-2000 than in 1998-1999, likely
reflecting the increased awareness of treatment options for glaucoma. The market share increase
for Patanol® was actually lower this year than last. Contributing to the lower market share for
Patanol® was the introduction of several new products to the anti-allergy ophthalmic market.
In fact, two of these newer products, Zaditor® and Alocril®, together made up the lost market
share for Patanol®. This type of growth in this market is likely to be challenged as healthcare
plans begin to question the practice of concurrent use of oral antihistamines and ophthalmic
antihistamines. The prevailing theme in the ophthalmic class this year was increased market
share for brands and decreased marketshare for generics. This year marked the first time in
four years that the generic market share in the ophthalmic class declined. The decrease is an
example of a phenomenon in which new drug sub-classes now treat conditions formerly treated
by generics.
COST
FORECAST
Penicillins also experienced mix trend of greater than 8 percent but for different reasons. Penicillins
are dominated primarily by generics with a 76.6 percent market share and secondarily by
Augmentin® with a 23.3 percent share. Augmentin®, with an average prescription cost of over
three times the class average, increased market share by 1.6 percent, accounting for virtually all
of the therapeutic mix change. However, penicillins also had the greatest impact of strength mix
among the top 25 classes. This was due to dramatic increases in market share of higher strength
suspension dosage forms of Augmentin® and Amoxil®.
Two other classes, cough/cold and ophthalmics, had mix trend of greater than 5 percent.
Cough/cold rose five positions from 12th in 1998-1999 to 7th in 1999-2000. The total cough/cold
increase was comprised of a slightly below-average increase in therapeutic mix of 3.4 percent
and a healthy almost 2 percent increase in strength mix. Much of the therapeutic mix increase
was due to increased market share of the non-sedating antihistamine/decongestant combination
products Claritin-D® and Allegra-D®. These two products increased market share within the class
by 2.6 percent. The strength mix component was relatively high because of a shift from the less
expensive 12-hour formulation of Claritin-D® to the more expensive 24-hour formulation.
TRENDS IN
EXPENDITURES
Anticonvulsants also experienced a total mix trend of almost 9 percent due to the large market
share increase of expensive drugs. Neurontin®, costing about 1.5 times the class average,
increased market share by 4.5 percent. Topamax®, at 2.4 times the class average, increased
market share by 1.5 percent and contributed about one-half as much as Neurontin® to the class
mix trend. Both products are indicated for seizures, but Neurontin® can be used as monotherapy
for adults as well as for children. (Neurontin® also is used off-label for pain control.) Topamax®
is indicated as adjunct therapy for adults only.
Antidiabetics rose from 15th in the 1998-1999 ranking to sixth in the 1999-2000 ranking, with
a 7.3 percent mix trend increase. In the 1997-1998 mix ranking, the antidiabetic class was
ranked first due to the popularity and the relatively high price of Rezulin®, the first glitazone on
the market. By the time Rezulin® was pulled from the market in early 2000 due to concerns about
liver toxicity, two new glitazones — Avandia® and Actos® — had been introduced in the United
States. While not quite as costly as Rezulin®, they are both more than twice the class average cost.
Not only have Avandia® and Actos® replaced Rezulin®, they have contributed to a 55-percent rise
in the market share of glitazones in the antidiabetic class, accounting for most of the mix trend
increase from 1999 to 2000.
INTRODUCTION
DRUG
IMPORTANCE
The 13.4 percent mix trend increase in the narcotic analgesic class was split between a 10.7 percent increase in therapeutic mix and a 2.7 percent increase in strength mix. The therapeutic mix
increase has been driven by increased use of more powerful products such as OxyContin®. After
increasing market share by only 0.8 percent from 1998-1999, the OxyContin® market share
rose 1.3 percent from 1999-2000, contributing to almost one half of the class mix increase.
The average AWP prescription cost of OxyContin® is $207.42 compared to the class average of
$30.09 in 2000. The strong strength mix component of trend was due to the release of the
160mg strength of OxyContin® in 2000.
PREFACE
ACTIONS
TABLE OF
CONTENTS
TABLE OF
CONTENTS
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TABLE OF
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TABLE OF
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The 1-percent change in the cost per prescription due to changes in the number of units per
prescription was the highest level seen since 1996-1997. Despite the increased impact of this
component over last year, as seen in Table 6, many of the same classes appear in the top five.
Cough/cold, narcotic analgesics and antihistamines, all consistently in the top five, secured
the top three positions from 1999-2000.
INTRODUCTION
TRENDS IN
EXPENDITURES
COST
FORECAST
% Change
3.8%
2.8%
2.7%
2.4%
2.3%
1.6%
1.6%
1.5%
1.5%
1.4%
1.4%
1.3%
1.2%
1.0%
1.0%
0.9%
0.5%
0.4%
0.3%
0.2%
0.2%
0.1%
-0.1%
-0.5%
-0.9%
1.2%
0.2%
100.0%
1.0%
The narcotic analgesic trend is likely continuing to show the use of these products in the treatment of long-term pain rather than only on a short-term basis such as after surgical procedures.
However, a potential danger in long-term use of these products is that patients may become
dependent on them, requiring greater quantities per prescription.
One other class worth noting in this analysis is the anti-rheumatic class. The impact of units
per prescription jumped from 1 percent last year to 2.3 percent this year. This was the first year
during which COX-2s were included in the common drugs and they displayed some of the higher
increases in units per prescription.
NEW DRUGS
APPENDIX A
APPENDIX A
The significance of new drugs in the use and cost of prescription drugs continued to grow in
2000. In 1999, drugs introduced since 1992 accounted for 40.8 percent of costs and 25.4 percent
of prescriptions. By 2000, new drugs introduced since 1992 accounted for 46.7 percent of 2000
cost and 29.6 percent of prescription use (see Figure 5). In 2000, 27 new drugs and six biologic
agents were approved by the FDA, compared with the introduction of 35 new drugs and five
biologics in 1999.18 However, unlike the recent past, the impact of drugs introduced in 2000 was
minimal. Drugs sold for the first time in the United States accounted for only 0.3 percent of overall 2000 PMPY AWP ingredient costs. The two drugs introduced in 2000 that had the largest cost
impact were Protonix® and Lotronex®, each of which accounted for only 0.1 percent of total PMPY
drug costs. (See Table 7) Protonix® is facing stiff market challenges from its competitors Prilosec®
and Prevacid®. In addition, the generic version of Prilosec® likely will be available late in 2001
and another PPI, Nexium®, was brought to market in early 2001. Lotronex®, used to treat irritable
bowel syndrome, was taken off the market in November 2000 due to reports of severe side effects.
ACTIONS
ACTIONS
3.9%
4.9%
3.0%
1.5%
4.0%
2.9%
4.1%
6.5%
3.1%
4.8%
3.3%
2.6%
3.1%
2.1%
3.6%
4.4%
1.6%
3.4%
2.2%
6.0%
1.2%
3.4%
3.1%
1.3%
1.4%
81.4%
18.6%
DRUG
IMPORTANCE
Total
% Rxs
COST
FORECAST
Cough/Cold
Narcotic Analgesics
Antihistamines
Decongestants
Anti-Rheumatics (NSAIDS)
Calcium Blockers
Gastrointestinals
Antihypertensives
Beta Blockers
Estrogens
Oral Contraceptives
Thyroid
Dermatologicals
Macrolides
Antidiabetics
Antihyperlipidemics
Cephalosporins
Penicillins
Antianxiety Agents
Antidepressants
Corticosteroids
Antiasthmatics
Diuretics
Ophthalmic Products
Anticonvulsants
Top 25
Other
TRENDS IN
EXPENDITURES
DRUG
IMPORTANCE
PRICE CHANGES DUE TO CHANGES IN UNITS PER PRESCRIPTION 1999-2000,
TOP 25 THERAPY CLASSES BY PRESCRIPTIONS IN 2000
INTRODUCTION
Another class of respiratory drugs, decongestants, made a strong showing in the units trend
ranking, showing up in the fourth place ranking at 2.4 percent. Consisting primarily of nasal
steroids, the decongestant class is likely benefiting from the same trend toward preventing
reactions to allergens rather than treating the attacks after they have occurred.
TABLE 6:
Therapy Class
The cough/cold and antihistamines classes usually track closely to each other because Claritin-D®
and Allegra-D® are the most commonly dispensed cough/cold products, while their sister products
Claritin® and Allegra® dominate the antihistamines. Increased units in these classes are likely an
indication that these types of drugs are being used to treat allergies on a prophylactic basis
rather than just to treat them symptomatically.
PREFACE
PREFACE
UNITS PER PRESCRIPTION
20 EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
21
APPENDIX B
APPENDIX B
18 The Pharmaceutical Research and Manufacturers of America (PhRMA). New drug approvals of 2000. Published January
18, 2001. www.phrma.org/publications/documents/backgrounders/2001-01-18.197.pdf Accessed March, 2001.
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TABLE OF
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TABLE OF
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22501_ii58
New 1995
New 2000
FIGURE 6
New 1994
New 1999
PERCENT OF AWP ACCOUNTED FOR BY NEW DRUGS
New 1998
%
PREFACE
%
100
INTRODUCTION
80
60
40
20
New 1993
INTRODUCTION
Total Existing
IMPACT OF NEW DRUGS INTRODUCED SINCE 1992 ON 2000 UTILIZATION AND COST
PREFACE
New 1996
rose to 4.7 percent in 2000. This dramatic increase is a function not only of these drugs being
blockbusters, but also due to the time it takes for new products to become part of the everyday
treatment arsenal used by physicians. Clearly, the advent of DTC advertising may quicken the
growth of a product’s market share. Indeed, from January through September of 2000, Vioxx®
ranked first in terms of DTC advertising with $138.3 million spent on such promotion. One of
the reasons for this heavy consumer advertising is that, unlike its competitor product Celebrex®
which was available in January 1999, Vioxx® did not come to market until May and had to
compensate for this later market entry.
FIGURE 5
New in 2000
New in 1999
0
New 1992
TABLE 7
COST
FORECAST
New in 1995
TOP NEW DRUGS IN 2000
PO
PO
SQ
PO
PO
PO
PO
IJ
PO
PO
OP
PO
PO
PO
IJ
PO
PO
VG
PO
TP
Feb-00
Feb-00
Dec-99
Jan-00
Apr-00
Jul-00
Nov-99
Aug-99
Apr-00
Apr-00
Dec-99
Aug-00
Oct-99
May-00
Jul-99
Dec-99
Mar-00
Jun-00
Feb-00
Jul-00
4
New in 1994
Primary Indication
% AWP
Cost
Gastroesophageal Reflux Disease
Irritable Bowel Syndrome (IBS)
Diabetes Mellitus/Hyperglycemia
Partial Seizures
Osteoarthritis
Type 2 Diabetes
Epilepsy
Pituitary Suppression
Alzheimer’s
Enterococcus
Allergic Conjunctivitis
Migraine
Breast Cancer
Hyperlipidemia
Ovarian Hyperstimulation
T-cell Lymphoma
Epilepsy
Yeast Infections
Sjogren’s Syndrome
Unwanted Facial Hair
0.1%
0.1%
0.0%
0.0%
0.0%
0.0%
0.0%
0.0%
0.0%
0.0%
0.0%
0.0%
0.0%
0.0%
0.0%
0.0%
0.0%
0.0%
0.0%
0.0%
2
New in 1993
0.3%
All New Drugs
0.3%
All Other Drugs
99.7%
All Drugs
100.0%
22 EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
1993
1994
1995
1996
1997
1998
1999
2000
As we look ahead five years, the number of new drugs coming to market will increase dramatically.
The potential explosion of new drug products is even more dramatic when current drug pipeline
activity is examined. According to SG Cowen, 1,010 products are in the development pipeline. Of
these products, 152 are in preclinical trials, 699 are in phase I, II or III clinical trials, and an
additional 159 products have been filed with the FDA.19 However, based on our analysis of existing
pipeline products, we think very few blockbuster drugs will come to market over the next five years.
The rough map of the Human Genome, completed ahead of schedule in the summer of 2000,
marked a giant step toward development of drugs to combat such diseases as breast cancer,
hereditary deafness and skeletal disorders, hemorrhagic strokes, kidney disorders and one type of
diabetes. Over the next three to five years, as researchers locate the exact position of all 35,000+
genes on human chromosomes and sequence millions of base pairs, drugs targeted to specific
conditions with pinpoint accuracy will begin to emerge. Eventually, research may enable scientists
to predict who will respond most effectively to a particular drug therapy, or who may suffer a
side effect, as well as yield designer drugs targeted to each individual’s unique genetic profile
and engineered in a much more precise way than today’s drugs. This information may also be
used to determine an individual’s susceptibility to common disorders, allowing the design of
programs for effective, individualized, preventive medicine focused on lifestyle changes.
19 SG Cowen Securities. Pipeline Pulse. March 2001.
23
APPENDIX B
The number of drugs approved in a given year, however, is only one part of the story. Another
important factor is whether blockbuster drugs were among the products introduced. In 1999,
new drugs accounted for 1.6 percent of total costs, largely on the strength of Celebrex® and
Vioxx® (See Figure 6 and Table 8). The contribution of all 1999 new drugs to total annual costs
New in 1992
1992
APPENDIX A
PO – Oral, SQ – Injected under the skin, IJ – Injected, OP – Opthalmic, VG – Vaginal, TP – Topical
0
ACTIONS
PROTONIX®
LOTRONEX®
HUMALOG MIX 75/25®
TRILEPTAL®
MOBIC®
GLUCOVANCE®
KEPPRA®
REPRONEX®
EXELON®
ZYVOX®
ALOCRIL®
DEPAKOTE ER®
AROMASIN®
WELCHOL®
FOLLISTIM/ANTAGON®
TARGRETIN®
ZONEGRAN®
GYNAZOLE-1®
EVOXAC®
VANIQA®
FDA
Route Approval Date
Top 20 New Drugs
APPENDIX A
New in 1996
6
DRUG
IMPORTANCE
DRUG
IMPORTANCE
New in 1997
COST
FORECAST
ACTIONS
10
8
Drug Name
APPENDIX B
New in 1998
New 1997
% Cost
% Rxs
TRENDS IN
EXPENDITURES
TRENDS IN
EXPENDITURES
12
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PREFACE
TABLE OF
CONTENTS
22501_ii58
We are looking at nothing less than a new era in healthcare, one that promises incalculable
potential to eradicate diseases and improve quality and length of life. We cannot predict with
certainty when this promise will be fulfilled or how it may eventually impact pharmacy benefit
plans. What we can predict is that a new generation of biotech drugs is in our future, and both
the rewards and the costs will likely be high.
TABLE 8
APPENDIX B
APPENDIX A
ACTIONS
DRUG
IMPORTANCE
COST
FORECAST
TRENDS IN
EXPENDITURES
INTRODUCTION
PERCENT OF 2000 COST AND AWP COST PER PRESCRIPTION FOR TOP 50 NEW DRUGS
Year of
Introduction
2000
% Cost
2000
AWP/Rx
LIPITOR®
1997
1995
PREVACID®
®
CLARITIN
1993
®
1992
ZOLOFT
®
ZOCOR
1992
®
1999
CELEBREX
®
PAXIL
1993
®
1995
GLUCOPHAGE
®
VIOXX
1999
®
1992
NORVASC
®
ZITHROMAX
1992
®
1996
ALLEGRA
®
ZYRTEC
1996
®
1995
PREMPRO
®
NEURONTIN
1994
®
1998
CELEXA
®
ROXICODONE
1992
®
1992
ACCUTANE
®
FLONASE
1994
®
1998
SINGULAIR
®
AVANDIA
1999
®
1998
ENBREL
®
REBETRON 600
1998
®
1996
FLOVENT
AVONEX® ADMINISTRATION PACK 1996
®
1997
LEVAQUIN
AMBIEN®
1993
®
1999
ACTOS
®
LAMISIL
1996
®
1994
SEREVENT
®
FOSAMAX
1995
®
1995
HYZAAR
®
ZYPREXA
1996
®
1995
ULTRAM
®
NASONEX
1997
®
1995
LOTREL
®
CEFZIL
1992
®
1992
ASACOL
®
EVISTA
1998
®
1998
PLAVIX
®
RELAFEN
1992
®
1999
ACIPHEX
®
VALTREX
1995
®
1994
RISPERDAL
®
SERZONE
1995
®
1998
VIAGRA
®
DIOVAN
1997
®
1995
COZAAR
®
SPORANOX
1992
®
1998
ZOMIG
OTHER
7.7%
6.8%
4.0%
3.4%
3.3%
3.3%
3.0%
2.8%
2.5%
2.3%
2.2%
1.7%
1.7%
1.6%
1.5%
1.4%
1.4%
1.4%
1.3%
1.2%
1.1%
1.1%
1.1%
1.1%
1.1%
1.1%
1.0%
1.0%
0.9%
0.9%
0.9%
0.8%
0.8%
0.8%
0.7%
0.7%
0.7%
0.7%
0.6%
0.6%
0.6%
0.6%
0.6%
0.6%
0.6%
0.6%
0.5%
0.5%
0.5%
0.5%
22.3%
$83.41
$134.23
$71.93
$84.42
$116.86
$93.75
$82.66
$66.14
$83.03
$57.68
$39.57
$57.13
$54.94
$30.38
$118.24
$73.22
$177.48
$341.48
$54.94
$81.49
$124.01
$1,084.78
$1,241.78
$74.92
$856.32
$83.83
$58.26
$143.30
$224.22
$72.09
$69.49
$51.30
$256.54
$54.09
$53.80
$63.07
$68.35
$147.55
$71.06
$101.52
$77.97
$126.88
$92.88
$141.88
$78.81
$54.81
$46.12
$53.67
$237.44
$156.14
$87.39
100.0%
$83.07
Brand Name
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
Total
24 EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
22501_Tabs
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Page 3
COST
FORECAST
22501_ii58
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Page 25
TABLE OF
CONTENTS
2001-2005 DRUG COST TREND FORECAST
TRENDS IN
EXPENDITURES
COST
FORECAST
• 15.4 percent in 2001
• 12.7 percent in 2002
• 11.9 percent in 2003
• 11.6 percent in 2004
• 11.3 percent in 2005
INTRODUCTION
The remainder of this section contains Express Scripts’ annual projections for the next five years.
These projections are presented in the aggregate and for major therapy class groupings. In terms
of the former, Express Scripts projects that PMPY AWP ingredient costs will continue to rise but at a
reduced rate through 2005. More specifically, Express Scripts projects that drug costs will grow by:
PREFACE
Since Express Scripts began monitoring drug costs in 1993, PMPY AWP ingredient costs have
grown by an escalating annual rate. In the 1999 Drug Trend Report, PMPY drug costs were projected to rise marginally to 17.6 percent in 2000 before growing at a gradually declining rate
through 2004. As is evident, the actual 2000 PMPY cost estimate was 1.4 percentage points lower
than last year’s projection. In the aggregate, this over-estimate stems principally from the lower
than expected inflation rate — 6 percent anticipated versus 5.4 percent actual — and the minimal contribution of new drugs — 0.3 percent in 2000 versus 1.6 percent in 1999. Clearly, this
explanation is simplistic. The degree of variability across therapy classes in terms of all cost drivers is considerable. For example, we projected that 2000 PMPY costs for COX-2s would rise by
62 percent and that costs for oral anti-diabetic drugs would grow by 17 percent. In fact, these
costs grew by 152.2 percent and 29.6 percent, respectively. Similarly, we estimated that PMPY
costs for PPIs and medications used to treat women’s health conditions would rise by 32 percent
and 17.2 percent, respectively; but they actually grew by 28.6 percent and 12.2 percent, respectively.
DRUG
IMPORTANCE
ACTIONS
These projections translate into an 81 percent increase in PMPY costs over the next five years
from $449.74 in 2000 to $815.17 in 2005 (see Figure 7). As was the case in building last year’s
estimate, the assumption regarding the inflation rate that will occur through 2005 is a key factor
influencing the magnitude of the projected rates of cost increases. As was discussed in the price
portion of this Report, inflation for prescription drugs was 5.1 percent in 1998 and 5.4 percent in
both 1999 and 2000. Express Scripts anticipated that price hikes would grow to 6 percent in
2000, and diminish thereafter, largely because the political environment was becoming somewhat
hostile toward the pharmaceutical industry. It was expected that the industry probably would
react to this pressure by increasing prices significantly during 2000 before reducing the level of
price increases as it did during the healthcare reform debate that took place during the initial
Clinton administration.
APPENDIX A
APPENDIX B
25
6/4/01
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Page 26
TABLE OF
CONTENTS
TABLE OF
CONTENTS
22501_ii58
FIGURE 7
FIGURE 8
PERCENT CHANGES IN AWP COST 1995-2005
815
$
800
655
15
519
560
TRENDS IN
EXPENDITURES
15.4
12.8
Inflation
12.7
11.9
11.6
11.3
400
10
330
243
282
240
5
3.3
0
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
(2001–2005 projected)
5.4
5.4
5.5
5.0
5.0
5.0
5.0
97/98
98/99
99/00
00/01
01/02
02/03
03/04
04/05
2.4
0
95/96
96/97
(00/01–04/05 projected)
Although these assumed inflation rates were applied to all classes, a number of other factors
were also considered. First, actual 2000 costs and utilization were carefully analyzed. Then other
considerations — including aging of the population, anticipated utilization and product mix,
products losing patent status and introduction of new products — were factored into the therapy
class specific projections. Express Scripts’ annual PMPY cost estimates from 2001 through 2005
are presented in the aggregate and for major therapeutic classes, along with a brief rationale
for these projections in Table 9. Key new drugs and patent expirations that were considered in
developing our cost projections for each therapy class are highlighted.
DRUG
IMPORTANCE
ACTIONS
APPENDIX A
Against this backdrop and despite initiatives in states such as Maine and Vermont, Express
Scripts has altered its inflation assumptions upward from last year’s estimates to 5.5 percent in
2001 and 5 percent annually from 2002 through 2005. The relationship between our overall PMPY
cost projections and our inflation assumptions is depicted graphically in Figure 8.
APPENDIX A
26 EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
27
APPENDIX B
APPENDIX B
COST
FORECAST
Medicare prescription drug coverage was clearly one of the central issues debated during the
Bush-Gore presidential campaign. Both candidates promised to tackle this issue, albeit in different
ways, if elected. Gore essentially proposed grafting on prescription drug coverage to the current
Medicare benefit, while Bush suggested that the federal government fund states to provide such
coverage while the federal government grappled with how to restructure Medicare and fold
prescription coverage into that new scheme. With Bush winning the presidency, the urgency of
passing Medicare prescription drug benefit legislation is not as paramount as it likely would
have been had Gore won. President Bush’ priorities appear to be tax reduction, education, military
spending and then Medicare prescription drug coverage. At least one short-term result of the Bush
Administration’s agenda is reduced political pressure regarding this issue. The accompanying
attention paid to high prescription drug costs and other ancillary charges related to manufacturer
pricing practices and profit margins as well as to government indirect underwriting of some drug
discovery has also diminished. In addition, the disappearance of an industry-perceived threat
that a Gore election would increase the likelihood of indirect or direct prescription cost controls
seems to have reduced the pressure on the industry to curb price increases.
5.1
TRENDS IN
EXPENDITURES
COST
FORECAST
16.2
387
80
DRUG
IMPORTANCE
PMPY Cost
17.4
450
480
160
ACTIONS
16.8
INTRODUCTION
INTRODUCTION
16.1
585
640
320
20
730
720
%
PREFACE
PREFACE
PER MEMBER PER YEAR AWP COSTS 1996-2005
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Page 28
TABLE OF
CONTENTS
TABLE OF
CONTENTS
22501_ii58
TABLE 9
Gastrointestinal
PPIs
$34.23
$23.99
18.4%
28.6%
$40.53
$30.86
18.4%
23.5%
$47.97
$38.11
10.0%
12.0%
$52.74
$42.69
5.8%
6.0%
$55.78
$45.25
9.2%
10.0%
$60.89
$49.77
6.7%
7.0%
$64.97
$53.26
$8.91
$1.33
-7.1%
4.5%
$8.28
$1.39
0.5%
10.5%
$8.32
$1.54
0.0%
13.0%
$8.32
$1.74
3.0%
13.0%
$8.57
$1.96
5.0%
8.0%
$9.00
$2.12
5.0%
7.0%
$9.45
$2.27
Central Nervous
System (CNS)
Antidepressants
$52.95
$33.68
20.3%
17.4%
$63.72
$39.55
16.8%
14.5%
$74.43
$45.28
14.5%
11.0%
$85.24
$50.27
15.2%
12.0%
$98.20
$56.30
15.6%
12.0%
$113.55
$63.05
16.2%
12.0%
$131.91
$70.62
Anticonvulsants
$7.13
29.9%
$9.26
27.5%
$11.81
28.0%
$15.11
29.0%
$19.49
31.0%
$25.54
32.0%
$33.71
Antianxiety Agents
$6.96
15.1%
Antipsychotics
$3.10
31.0%
$8.01
9.5%
$8.77
8.0%
$9.47
7.0%
$10.14
6.0%
$10.74
6.0%
$11.39
$4.06
27.5%
$5.18
24.0%
$6.42
20.0%
$7.70
17.0%
$9.01
15.0%
$10.36
Hypnotics
Antihyperlipidemics
$2.08
$26.17
36.5%
23.4%
$2.84
$32.28
19.5%
20.5%
$3.39
$38.90
17.0%
18.0%
$3.97
$45.90
15.0%
16.0%
$4.57
$53.24
14.0%
14.0%
$5.21
$60.70
12.0%
13.0%
$5.83
$68.59
Cardiovascular
Antihypertensives
$44.72
$20.37
11.8%
16.6%
$50.00
$23.74
10.5%
13.5%
$55.27
$26.94
7.1%
7.0%
$59.21
$28.83
7.7%
8.0%
$63.77
$31.14
7.6%
8.0%
$68.61
$33.63
7.7%
8.0%
$73.87
$36.32
Calcium Blockers
Beta Blockers
$13.77
$7.70
2.5%
15.7%
$14.11
$8.91
3.5%
13.5%
$14.60
$10.11
3.0%
12.0%
$15.04
$11.33
3.0%
12.0%
$15.49
$12.69
3.0%
11.0%
$15.96
$14.08
3.0%
11.0%
$16.44
$15.63
$2.89
12.1%
$3.24
11.5%
$3.61
11.0%
$4.01
11.0%
$4.45
11.0%
$4.94
11.0%
$5.48
Pain/Inflammation
Anti-Rheum (NSAIDS)
Cox-2s
Narcotic Analgesics
$33.57
$13.16
$4.77
$9.24
31.9%
-3.6%
152.2%
34.8%
$44.27
$12.69
$12.03
$12.46
20.2%
-0.5%
45.5%
22.5%
$53.23
$12.63
$17.50
$15.26
15.2%
0.0%
25.0%
20.0%
$61.32
$12.63
$21.88
$18.32
13.6%
1.0%
20.0%
17.0%
$69.66
$12.75
$26.26
$21.43
11.7%
2.0%
15.0%
15.0%
$77.81
$13.01
$30.19
$24.64
11.5%
5.0%
15.0%
12.0%
$86.74
$13.66
$34.72
$27.60
Migraine Products
Diabetes
Oral
Insulin
$6.40
$14.82
$11.79
$3.03
10.9%
25.9%
29.6%
11.6%
$7.09
$18.66
$15.28
$3.38
10.5%
16.1%
17.5%
9.5%
$7.83
$21.66
$17.95
$3.70
8.5%
15.1%
16.0%
11.0%
$8.50
$24.93
$20.83
$4.11
8.5%
14.5%
15.0%
12.0%
$9.22
$28.55
$23.95
$4.60
8.0%
13.2%
14.0%
9.0%
$9.96
$32.32
$27.30
$5.02
8.0%
12.2%
13.0%
8.0%
$10.76
$36.27
$30.85
$5.42
Respiratory
Antiasthmatics
$43.04
$13.67
10.9%
12.7%
$47.73
$15.40
12.1%
14.5%
$53.50
$17.63
11.1%
13.0%
$59.43
$19.93
10.2%
13.0%
$65.51
$22.52
8.8%
12.0%
$71.25
$25.22
8.8%
12.0%
$77.53
$28.24
Antihistamines
$13.96
14.2%
$15.95
11.5%
$17.78
11.0%
$19.74
9.0%
$21.52
6.0%
$22.81
6.0%
$24.18
INTRODUCTION
TRENDS IN
EXPENDITURES
COST
FORECAST
DRUG
IMPORTANCE
ACTIONS
%
Change
%
Change
2004
$PMPY
%
Change
2005
$PMPY
5.6%
$9.54
11.0%
$10.59
9.5%
$11.60
8.5%
$12.58
7.5%
$13.52
7.5%
$14.54
7.3%
13.3%
-2.7%
-7.5%
$6.84
$13.36
$10.02
$3.85
9.5%
10.0%
16.8%
1.0%
$7.49
$14.70
$11.70
$3.89
9.0%
10.0%
17.9%
2.0%
$8.16
$16.17
$13.79
$3.97
9.0%
10.0%
16.5%
2.0%
$8.90
$17.78
$16.07
$4.05
9.0%
10.0%
15.3%
2.0%
$9.70
$19.56
$18.52
$4.13
9.0%
10.0%
13.0%
2.0%
$10.57
$21.52
$20.92
$4.21
$2.98
$0.19
5.7%
1094.7%
$3.15
$2.27
7.5%
58.5%
$3.39
$3.60
7.0%
47.0%
$3.62
$5.29
7.0%
35.0%
$3.88
$7.14
7.0%
28.0%
$4.15
$9.14
7.0%
21.0%
$4.44
$11.06
Other/Flu
Women’s Health
Estrogens
Oral Contraceptives
Misc. Endocrine
$2.97
$24.07
$9.59
$9.18
$5.31
-74.7%
12.2%
12.5%
1.8%
29.9%
$0.75
$27.02
$10.79
$9.34
$6.89
10.5%
16.3%
11.0%
10.5%
32.5%
$0.83
$31.43
$11.98
$10.32
$9.13
10.0%
15.1%
9.0%
10.0%
29.0%
$0.91
$36.18
$13.05
$11.35
$11.78
10.0%
14.1%
7.0%
10.0%
26.0%
$1.00
$41.30
$13.97
$12.49
$14.84
10.0%
13.7%
5.0%
10.0%
25.0%
$1.10
$46.95
$14.67
$13.74
$18.55
10.0%
14.1%
4.0%
10.0%
25.0%
$1.21
$53.55
$15.25
$15.11
$23.19
Anti-Infectives
Macrolides
$27.58
$8.18
2.8%
-2.1%
$28.37
$8.01
9.9%
8.5%
$31.17
$8.69
9.8%
8.0%
$34.21
$9.39
9.6%
8.0%
$37.49
$10.14
9.0%
8.0%
$40.85
$10.95
8.8%
8.0%
$44.43
$11.82
Cephalosporins
$7.65
-9.3%
$6.94
0.5%
$6.97
1.0%
$7.04
2.0%
$7.19
3.0%
$7.40
4.0%
$7.70
Penicillins
$6.78
9.0%
$7.39
11.5%
$8.24
10.0%
$9.06
9.0%
$9.88
8.0%
$10.67
7.0%
$11.42
Quinolones
$4.97
21.3%
$6.03
20.5%
$7.27
20.0%
$8.72
18.0%
$10.29
15.0%
$11.83
14.0%
$13.49
Herpes
Hepatitis
28 EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
Growth rate will moderate as market reaches
saturation; generic Prilosec will lower per Rx cost
Utilization will continue to shift to PPIs
New drugs for IBS will offset decreased use
of other drugs
New indications for existing products will increase use;
generic Prozac will decrease cost
Shift from traditional to newer products and use of
Neurontin and successor product pregabalin for pain
relief will drive up costs
Little growth expected because of growing
preference for SSRIs for treatment of anxiety
Increased use of new branded products and expanded
indications will drive up costs
Increase in use of new branded products will grow costs
With aging of poulation and DTC, expect high growth
to continue
Expected generic availibility of serveral ACE inhibitors
will slow growth
Continued erosion of class use expected
Use for heart failure and first-line use for hypertention
will increase utilization
Rise in use due to JNC-6 guidelines pushing first-line
use for HTN
Cox-2s continue to erode market share of branded NSAIDS
Continued high use will moderate over time
Use will continue to increase as will use of more
expensive products
Modest increases expected to continue
Growing use will drive up class cost
New modes of administration will increase utilization
primarily for Type II
Utilization grows marginally but use of more expensive
products pushes costs up
Significant but declining utilization increases but generic
Claritin will moderate costs beginning in 2003
Modest increases anticipated unless bad flu/allergy
season; use of expensive products will continue
Growth will be moderate unless bad allergy season
Price increases will drive class costs
Cost growth will be minimal due to standardization of
treatment
Modest growth will continue
Utilization growth and introduction of pegylated interferon/ribavirin product will further increase costs
Rise in use dependent on severity of flu season
Declining use somewhat offset by price increases
Modest growth as more plan sponsors cover OCs
Aging of the population, massive undertreatment of
osteoporosis and fear of using estrogens will lead to
substantial utilization growth
Physician preference for use in respiratory infections
will continue; use dependent on severity of flu season
Market for these products supplanted by quinolones
and macrolides
Utilization declines as preference for other antibiotic
classes expands but use of Augmentin will grow
Growth in class costs will increase despite Cipro
going generic in 2003
29
APPENDIX B
$9.03
$6.38
$11.79
$10.30
$4.16
Decongestants/Nasal Steroids
Dermatologicals
Antivirals
HIV
Comments
APPENDIX A
APPENDIX A
2001 Est.
$PMPY
ACTIONS
APPENDIX B
Cough/Cold
%
Change
DRUG
IMPORTANCE
2003
$PMPY
Diuretics
2000
$PMPY
COST
FORECAST
2002
%
$PMPY Change
H2RAs
Other
%
Change
TRENDS IN
EXPENDITURES
1999
$PMPY
INTRODUCTION
Therapy Class
PREFACE
PREFACE
DRUG TRENDS: ALL DRUGS 1999-2000 SUMMARY AND 2001-2005 FORECAST
6/4/01
2:58 PM
Page 30
PREFACE
INTRODUCTION
The most significant development in the gastrointestinal drug class is the expiration of the
Prilosec® patent, currently scheduled for October 2001. Prilosec® was the top-selling drug in
2000 in the United States. Approved in early 2001, Nexium®, a drug derived from Prilosec®, is
expected to compete with generic forms of Prilosec® as well as with the other branded proton
pump inhibitors (Prevacid®, Aciphex® and Protonix®). Other GI drugs in advanced clinical trials
include Zelmac®, which will likely be approved in 2001 for the treatment of irritable bowel
syndrome, and the Substance P inhibitor MK-869, which is being studied for chemotherapyinduced nausea and vomiting.
Prozac® was at the center of two important developments in the central nervous system (CNS)
drug class in 2000. First, the courts ruled that the patent for Prozac® expired in 2001, not 2003
as originally thought. Second, the development of an expected replacement for Prozac®, r-fluoxetine,
was discontinued after clinical trials showed evidence of cardiovascular toxicity. A new product,
duloxetine, is being developed to possibly replace Prozac® in the antidepressant market. An
unnamed product in advanced clinical trials treats depression by inhibiting a brain chemical
called substance P. A product in development for attention-deficit hyperactivity disorder, atomoxetine, shows promise for two reasons: first, it treats the disease differently than other available
products; and second, it is not a narcotic, which should limit abuse and make it easier for schools
to store and administer the drug. A pipeline product that may have a broad range of uses is the
anticonvulsant pregabalin, which is expected on the market in 2002. Similar to Neurontin®,
pregabalin may have indications for both epilepsy and pain when it is approved.
NEW PRODUCTS:
Expected Release Date
2001 2002 2003 2004 2005
Brand name
Generic name
Proposed Use
Nexium®
esomeprazole
GERD, PUD
X
Zelmac®
tegaserod
IBS
X
MK-869
Chemotherapyinduced vomiting
NEW PRODUCTS:
Brand name
Generic name
X
GERD
X
Geodon®
ziprasidone
Psychosis
X
cilansetron
IBS
X
Reminyl®
galantamine
Alzheimer’s
X
Zomaril®
iloperidone
Psychosis
X
aripiprazole
Psychosis
X
Prevacid® – 2005
®
Aciphex – 2004
Vestra®
duloxetine
Depression
reboxetine
Depression
X
X
escitalopram
Depression
X
pregabalin
Epilepsy, pain
X
atomoxetine
Attention-deficit
hyperactivity disorder
DRUG
IMPORTANCE
DRUG
IMPORTANCE
Prilosec – 2001
Axid® – 2002
COST
FORECAST
®
Expected Release Date
2001 2002 2003 2004 2005
norcisapride
Patent expirations:
Pepcid® – 2001
Proposed Use
X
substance P
inhibitor
TRENDS IN
EXPENDITURES
TRENDS IN
EXPENDITURES
CENTRAL NERVOUS SYSTEM
INTRODUCTION
GASTROINTESTINAL
PREFACE
COST
FORECAST
TABLE OF
CONTENTS
TABLE OF
CONTENTS
22501_ii58
X
olanzapine
Psychotic depression
GW320659
Attention-deficit
hyperactivity disorder
Ariza®
X
Depression
X
memantine
Alzheimer’s
X
leteprinim
Alzheimer’s
Neurontin® – expired,
Serzone® – 2003
X
APPENDIX A
APPENDIX A
Neotrofin®
Patent expirations:
BuSpar® – 2001
®
Prozac – 2001
but competition
delayed until 2002
30 EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
®
Celexa – 2003
Zofran® – 2005
Zoloft® – 2005
®
Wellbutrin SR – 2004
31
APPENDIX B
APPENDIX B
X
ACTIONS
ACTIONS
fluoxetine/
6/4/01
2:58 PM
Page 32
PREFACE
INTRODUCTION
PAIN/INFLAMMATION
A number of new products are in the short-term pipeline for the treatment of respiratory disease,
but most are similar to existing products. Clarinex® a derivative of Claritin®, and Soltara® a derivative of Hismanal®, are two antihistamines that have been submitted to the FDA for approval. Two
unique products for the treatment of chronic obstructive pulmonary disease, Ariflo® and Viozan®,
are in late-stage clinical trials. One unique product expected on the market shortly is Xolair®,
which is being studied in both asthma and allergic rhinitis. Xolair® works by antagonizing the
effects of IgE, which is an inflammatory protein found in the lungs.
This therapeutic category contains drugs for general pain, osteoarthritis, rheumatoid arthritis
and migraine headaches. With the success of the COX-2 inhibitors Celebrex® and Vioxx®, similar
products, including the first injectable product, parecoxib, are quickly being developed to compete
in this category. Enbrel® received a first-line indication for the treatment of rheumatoid arthritis
in 2000, and studies for its use in psoriasis are ongoing. Three additional triptans that are close
to approval will provide additional competition in this therapeutic category, although none
appears to offer improved safety or efficacy.
NEW PRODUCTS:
NEW PRODUCTS:
Generic name
Asmanex®
mometasone
Asthma
Foradil®
formoterol
Asthma
X
Clarinex®
desloratadine
Allergic rhinitis
X
Soltara®
norastemizole
Allergic rhinitis
Zyrtec-D®
cetirizine/
Allergic rhinitis/
pseudoephedrine
congestion
olizumab*
Asthma,
X
X
COST
FORECAST
SB-207499
Viozan®
Spiriva
®
Nuvance®
Proposed Use
valdecoxib
Arthritis, pain
parecoxib*
Acute pain
etoricoxib
Arthritis, pain
COX-189
Arthritis, pain
anakinra*
Rheumatoid arthritis
X
Pain
X
Kineret®
X
Dirame®
propiram
Relpax®
X
X
X
X
D2E7
X
eletriptan
Migraine headache
X
COPD
X
Miguard®
frovatriptan
Migraine headache
X
COPD
X
Axert®
almotriptan
Migraine headache
X
Prosaptide®
TX-14
Neuropathic pain
Relafen® – 2002
Duragesic® – 2004
tiotropium
COPD
X
interleukin-4
Asthma
X
Asthma
X
COST
FORECAST
Ariflo
Expected Release Date
2001 2002 2003 2004 2005
Generic name
X
allergic rhinitis
®
Brand name
TRENDS IN
EXPENDITURES
Brand name
Xolair®
Proposed Use
Expected Release Date
2001 2002 2003 2004 2005
INTRODUCTION
RESPIRATORY
PREFACE
TRENDS IN
EXPENDITURES
TABLE OF
CONTENTS
TABLE OF
CONTENTS
22501_ii58
X
*injectable product
Symbicort®
formoterol/
budesonide
interleukin-4
Patent expirations:
Stadol® NS – 2001
Asthma
DRUG
IMPORTANCE
DRUG
IMPORTANCE
receptor
X
antagonist*
Patent expirations:
Flovent® – 2003
Flonase® – 2003
32 EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
33
APPENDIX B
APPENDIX B
APPENDIX A
APPENDIX A
Claritin® – 2002
ACTIONS
ACTIONS
*injectable product
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TABLE OF
CONTENTS
TABLE OF
CONTENTS
22501_ii58
CARDIOVASCULAR
WOMEN’S HEALTH
INTRODUCTION
NEW PRODUCTS:
NEW PRODUCTS:
Expected Release Date
2001 2002 2003 2004 2005
Brand name
Generic name
Proposed Use
Crestor®
rosuvastatin
Hyperlipidemia
X
omapatrilat
Hypertension
X
eplerenone
Hypertension,
X
Vanlev
®
Brand name
Generic name
Proposed Use
Bonviva®
ibandronate
Osteoporosis
arzoxifene
Cancer
lasofoxifene
Osteoporosis,
Fortéo®
teriparatide
Osteoporosis
Xyvion®
tibolone
Osteoporosis
Ortho Evra®
ethinyl estradiol/
Contraceptive patch
heart failure
roxifiban
Inhibition of platelet
X
X
breast cancer
X
X
aggregation
itavastatin
Hyperlipidemia
X
ezetimibe
Hyperlipidemia
prasterone
Lupus
ranolazine
Angina, CHF
X
estradiol/
Osteoporosis
melagatran
DVT prophylaxis
X
trimegestone
BAY 13-9952
Hyperlipidemia
X
avasimibe
Hyperlipidemia
X
X
norgestimate
Aslera®
X
X
X
Zometa®
zolendronate
Osteoporosis
Yasmin®
ethinyl estradiol/
Contraception
Seasonale®
ethinyl estradiol/
X
X
X
DRUG
IMPORTANCE
DRUG
IMPORTANCE
Hypertension
X
COST
FORECAST
COST
FORECAST
Lumaxis®
olmesartan
Expected Release Date
2001 2002 2003 2004 2005
TRENDS IN
EXPENDITURES
TRENDS IN
EXPENDITURES
Compounds from several different chemical classes fill the osteoporosis pipeline. Arzoxifene
and lasofoxifene are selective estrogen receptor modulators. Bonviva® and Zometa® are bisphosphonates. Xyvion® is a synthetic hormone with tissue-specific effects. Fortéo® is recombinant
parathyroid hormone, given by injection to patients with severe osteoporosis. Contraception
continues to be a major focus for pharmaceutical manufacturers, and while the compounds in
development offer only slight clinical differences over currently available products, they provide
women with different therapy options. Yasmin® contains a progestin not previously available in
the United States, Ortho Evra® is the first transdermal contraceptive, and Seasonale® will be
taken continuously for 91 days (84 days of active drug followed by 7 days of placebo tablets).
X
drospirenone
Patent expirations:
Mevacor® – 2001
Accupril® – 2002
Lotensin® – 2003
Plendil® – 2001
Zestril®/Prinivil®– 2002 Zocor® – 2005
INTRODUCTION
The most significant product in the short-term cardiovascular pipeline appears to be Crestor ,
which is a “statin” similar to Lipitor® and Zocor®. Early reports indicate that Crestor® may be the
most potent statin to date. Another high-profile product, Vanlev®, was originally expected on the
market in 2000, but concerns about side effects led to a new clinical study and a new launch
date of 2002. Ezetimibe is a cholesterol absorption inhibitor that is being studied in combination
with Zocor® in a fixed-dose regimen for the treatment of elevated cholesterol. Ranolazine, which
represents a new class of drugs called partial fatty acid oxidation inhibitors, is being studied in
chronic angina and heart failure. Several drugs in this class lose patent protection in the coming
years, including Mevacor®, the first statin.
PREFACE
PREFACE
®
Pravachol® – 2005
Contraception
X
levonorgestrel
Ortho-Novum® – 2003
34 EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
35
APPENDIX B
APPENDIX B
APPENDIX A
APPENDIX A
Nolvadex® – 2002
ACTIONS
ACTIONS
Patent expirations:
Estraderm® – 2001
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PREFACE
INTRODUCTION
TRENDS IN
EXPENDITURES
Drugs used to treat viral illness dominate the anti-infective pipeline. A significant number of
drugs are in development for HIV. Most of them, however, are similar to products already on the
market. The combination product Rebemax® is expected to replace Rebetron® as a therapy of
choice for some patients with hepatitis C. Approval of ribavirin as a stand-alone product, which
is expected in 2001, would expand use of ribavirin, which is currently available in the United
States only in Rebetron®. One intriguing product, Picovir®, is being studied as a treatment for
the common cold. Clinical trial results indicate that treatment with Picovir® slightly decreases
the duration of a cold, but whether these data can convince physicians to prescribe the product
remains to be seen.
The diabetes pipeline centers on the insulin product Exubera®. This product administers dry
powder human insulin by use of an inhaler rather than the traditional method of injection.
Exubera® is in Phase III trials for both Type 1 and Type 2 diabetes and should be available in
2002. Other oral insulin products are in earlier stages of development. Symlin® is a synthetic
version of the hormone amylin that helps regulate glucose metabolism.
NEW PRODUCTS:
Brand name
Generic name
Proposed Use
Exubera®
insulin, inhaled
Diabetes
Expected Release Date
2001 2002 2003 2004 2005
NEW PRODUCTS:
Brand name
Generic name
Proposed Use
Spectracef®
cefditoren
Respiratory
Ketek®
telithromycin
Respiratory
Factive®
gemifloxacin
Respiratory tract
Expected Release Date
2001 2002 2003 2004 2005
X
tract infection
Symlin®
GI-262570
Diabetes Type 2
PNU-182716
Diabetes Type 2
X
Diabetes
X
pramlintide*
X
Oralgen®
insulin, oral liquid
X
Diabetes
Macular edema
beta inhibitor
and retinopathy
faropenem
Multiple infections
Vfend®
voriconazole
Fungal infections
X
Coactinon®
emivirine
HIV
X
Patent expirations:
tenofovir
HIV
X
Amaryl® – 2005
X
X
HIV
X
HIV
pegylated
Hepatitis C
*injectable product
DRUG
IMPORTANCE
HIV
BMS-232632
X
COST
FORECAST
protein kinase-C
tract infection
tipranavir
X
Types 1 and 2
infection; urinary
GW-433908
X
Types 1 and 2
tract infection
Pegasys®
X
Types 1 and 2
TRENDS IN
EXPENDITURES
COST
FORECAST
DIABETES
INTRODUCTION
ANTI-INFECTIVES
PREFACE
DRUG
IMPORTANCE
TABLE OF
CONTENTS
TABLE OF
CONTENTS
22501_ii58
X
X
interferon
alfa-2b
Rebemax®
pleconaril
Common cold
T-20
HIV
X
X
pegylated
Hepatitis C
X
ACTIONS
ACTIONS
Picovir®
interferon
alfa-2a/ribavirin
RWJ-270201
Treatment of
X
ribavirin
Hepatitis C
Floxin® – 2003
Cipro® – 2003
Zithromax® – 2005
Ceftin® – 2003
Diflucan® – 2004
X
Patent expirations:
36 EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
37
APPENDIX B
APPENDIX B
Rebetol®
APPENDIX A
APPENDIX A
influenza
APPENDIX B
APPENDIX A
ACTIONS
DRUG
IMPORTANCE
COST
FORECAST
TRENDS IN
EXPENDITURES
INTRODUCTION
PREFACE
TABLE OF
CONTENTS
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DRUG
IMPORTANCE
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TABLE OF
CONTENTS
T H E G R O W I N G I M P O R TA N C E O F P R E S C R I P T I O N
D R U G S I N D I S E A S E T R E AT M E N T
COST
FORECAST
A continued supply of new drugs is coming to market: According to the Pharmaceutical
Research and Manufacturers of America, an estimated $26.4 billion was spent on research and
development in 2000 alone.
TRENDS IN
EXPENDITURES
The dynamics underlying these substantial cost increases are the same as those discussed in
previous editions of this Report. The key cost drivers are:
INTRODUCTION
The trend figures cited above reflect past experience with and future expectations about the
magnitude of drug cost increases if plan sponsors take no aggressive action to curb costs.
Indeed, plan sponsors that did take aggressive steps — such as increasing member financial
share of costs and implementing three-tier copays during the 2000 plan year experienced trends
of 8 percent or less during the year.
PREFACE
In last year’s edition of the Drug Trend Report, we projected that 2000 PMPY drug costs would
grow at a slightly faster rate than 1999, 17.4 percent to 17.6 percent. Actual 2000 data show that
for the first time since Express Scripts began monitoring drug cost trends in 1993, the rate of
growth in PMPY AWP ingredient costs declined — to 16.2 percent. Although inflation was somewhat lower than anticipated, 5.4 percent versus the 6 percent projection, increases in per prescription costs, not utilization or new drugs, accounted for the lion’s share — almost 75 percent
— of the overall cost rise. By comparison, the growth in per-prescription costs represented onehalf of the overall 1998–1999 cost increase. Despite the promise of significant products going
generic over the next several years, it is anticipated that prescription drug costs will continue to
grow at a rapid but declining rate of growth over the next five years.
DRUG
IMPORTANCE
The demand for prescription drugs continues unabated, fueled by a society that looks to drugs
as a primary curative for all sorts of maladies: Some drugs are used by consumers in lieu of
changing behaviors or lifestyles, and other products enhance the quality of life. This phenomenon
has occurred with an apparent disregard for the possible known and unknown long-term effects
of some prescription drugs.
Consumer demand is also stimulated by DTC advertising: In a May 2001 press release, ScottLevin estimated that DTC spending for pharmaceuticals reached approximately $2.5 billion in
2000, more than double the amount spent in 1997.
APPENDIX A
Consumers are empowered: More and more Americans feel that it is their right to control the
healthcare services they receive.
ACTIONS
Consumers expect all prescription drugs should be available and accessible and that employers
or health plans should subsidize the cost of these drugs: Most Americans look at the drug benefit as an entitlement.
39
APPENDIX B
These forces do not operate in a vacuum but rather in a historical context of medical care
practice. That is, the seemingly never-ending flow of new pharmaceuticals and consumer
demand and empowerment have intersected with, and in some cases caused, a change in
the way diseases are treated.
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Page 40
%
100
PREFACE
90
70
Prescription Drugs
60
Physician and
Clinical Services
50
Hospital Care
40
30
Other
ACTIONS
1980
1990
1999
2010
(projected)
40
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
20 Delozier JE, Gagnon, RO. 1989 Summary: National Ambulatory Medical Care Survey. Advance data from Vital and Health
Statistics; no. 203. Hyattsville, MD: National Center for Health Statistics. 1991.
21 Woodwell DA. 1998 Summary: National Ambulatory Medical Care Survey. Advance data from Vital and Health Statistics;
no. 315. Hyattsville, MD: National Center for Health Statistics. 2000.
22 National survey of consumer reactions to direct-to-consumer advertising. In: Prevention Magazine. Emannaus Pa;
Rodale Press; 1998:6.
23 Office of Medical Policy, Division of Drug Marketing, Advertising, and Communications, Center for Drug Evaluation and
Research, U.S. Food and Drug Administration. Attitudes and behaviors associated with direct-to-consumer (DTC) promotion of prescription drugs. Main survey results. Published 2000. www.fda.gov/cder/ddmac/dtcindex.htm Accessed
February, 2001.
24 Reichert S, Simon T, Halm EA. Physicians’ attitudes about prescribing and knowledge of costs of common medications.
Archives of Internal Medicine. 2000;160:2799-2803. As cited in Managed Care Executive Edition, January 2001:8.
41
APPENDIX B
The decreased reliance on hospital care as measured by relative spending levels is not surprising.
The outcry in the late 1970s and 1980s over high and rising hospital costs led to a revolt over
fee-for-service payment systems that encouraged over utilization and unnecessary costs. Many
such systems were replaced by prospective, capitated payment schemes that encouraged efficiencies in the delivery of medical services. Such forces led not only to reduced costs per hospital
stay, but also to fewer inpatient admissions and to a consequent increase in the delivery of
medical services in outpatient settings. While some of these reductions in inpatient hospital
days resulted from the pruning of inappropriate admissions and excessive lengths of stay, in a
few instances prescription drugs enabled decreases in hospital days. That is, in the past many
diseases were treated with inpatient procedures — such as surgery for peptic ulcer disease or
electroconvulsive therapy in the case of severe depression; today prescription drugs taken in
ambulatory settings are treating these diseases.
APPENDIX A
APPENDIX A
0
ACTIONS
APPENDIX B
10
DRUG
IMPORTANCE
DRUG
IMPORTANCE
20
In sum, the practice of medicine has changed significantly over time. The relative importance of
pharmaceuticals has grown while the criticality of inpatient hospital care has declined. The role
of the PCP continues, and some would argue has gained prominence, particularly in the prescribing
arena, at the expense of the specialist. Finally, the relative power of the patient has grown and
the “control” of the physician over the patient has eroded. The remainder of this section presents
descriptions of how medical practice has changed for several important diseases and examines
the implications that these changes have on the pharmacy benefit.
COST
FORECAST
COST
FORECAST
80
In the last several years, consumers have become more active participants in their healthcare.
Today it is not unusual for a patient to walk into a physician’s office requesting that certain tests
be performed or that specific drugs be prescribed. DTC advertising for prescription drugs has
reinforced this consumer empowerment movement. The effectiveness of these campaigns in
generating consumer requests for and receipts of prescriptions for specific drugs has been well
documented.22, 23 In addition, another study found that 88 percent of the physicians surveyed did
not consider the cost of a medication when prescribing, and that 80 percent of the physician
respondents were unaware of the actual drug costs.24
TRENDS IN
EXPENDITURES
TRENDS IN
EXPENDITURES
FIGURE 9
PRESCRIPTION DRUGS, HOSPITAL CARE, AND PHYSICIAN AND CLINICAL SERVICES AS A
PERCENTAGE OF NATIONAL HEALTH EXPENDITURES 1980-2010
As the role of pharmaceuticals has grown and that of inpatient hospital treatment has declined,
primary care physicians (PCPs) — internists and general and family practitioners — have become
more critical players in treating patients who used to be seen primarily by specialists. Many patients
with hypertension, depression and other affective mood disorders, asthma and gastrointestinal
diseases are now being treated or at least monitored by their family physicians, not by cardiologists, psychiatrists, pulmonologists and gastroenterologists. Moreover, because of more convenient
dosing and substantially better side-effect profiles of many drugs, PCPs have become the principal
prescribers of legend drugs. The increased role of prescription drugs in medical treatment, particularly by PCPs, is further illuminated by the results of 1989 and 1998 National Ambulatory Medical
Care Surveys. According to data derived from these surveys, in 1989, 63.6 percent of physician
office visits were associated with drug mentions. By 1998, this figure had grown to 68.7 percent.
Furthermore, in 1998, 75.5 percent of visits to general/family practices and 78 percent of visits to
internal medicine offices included drug mentions. In contrast, only 59.2 percent of specialist visits
(excluding those to pediatricians, which had a 68.4 percent rate) had a drug mention.20, 21
INTRODUCTION
Healthcare Financing Administration (HCFA) data presented in the introduction of this Report
demonstrate the growth of prescription spending relative to overall national health expenditures.
When these HCFA data are further disaggregated, the increasing prominence of prescription
medicines in the medical care arsenal becomes more apparent. As is shown in Figure 9, reliance
on hospital-based care was much greater two decades ago than it was in 1999 and than what
is expected in 2010. In 1980, expenditures for hospital care represented 41.3 percent of national
health expenditures. This level, which dropped to 32.3 percent in 1999, is projected to decrease
further to 27.3 percent by 2010. Although they grew slightly from 19.2 percent in 1980 to 22.3
percent in 1999, expenditures for physician and clinical services are anticipated to decline to
20.7 percent in 2010. In contrast, outlays for prescription drugs as a percentage of national
health expenditures grew from 4.9 percent in 1980 to 8.2 percent in 1999. They are projected
to rise to 13.9 percent by 2010.
PREFACE
INTRODUCTION
TABLE OF
CONTENTS
TABLE OF
CONTENTS
22501_ii58
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PREFACE
INTRODUCTION
TRENDS IN
EXPENDITURES
MENTAL ILLNESS
While most medical services provided to cardiac patients are diagnostic or treatment oriented,
most cardiac drugs are preventive in nature. Drugs are used both for patients with existing heart
conditions and for people who have diseases that may lead to heart problems. Antihypertensives
and antihyperlipidemics are designed to prevent heart attacks and thereby save lives. The use
of cardiovascular medications, such as beta blockers, calcium blockers and angiotensinconverting enzyme inhibitors (ACEIs), became widespread beginning in the late 1970s, followed
by antihyperlipidemics and angiotensin receptor blockers (ARBs) in the late1990s. The aging of
the population, better education about hypertension and hyperlipidemia and lowered thresholds
for determining which patients should receive drug treatment have all contributed to increasing
numbers of people now taking drugs.25
ASTHMA
Not until the mid to late 1950s did effective drug therapies — neuroleptics and chlorpromazine
for people with schizophrenia, tricyclics and monoamine oxidase inhibitors for depressed people
and lithium carbonate for those suffering from bipolar disorders — begin to be used for treating
people with mental illnesses. The advent of these drugs, along with humanitarian concerns
about the conditions in asylums, led to the de-institutionalization movement that began in the
1970s. By the late 1980s, selective serotonin reuptake inhibitors (SSRIs) appeared on the market. Offering fewer side effects and better efficacy than previously available drug therapy, SSRIs
are more comfortable for non-psychiatrists to prescribe, as well as being less complicated for
patients to take. As they gained widespread use, some SSRIs demonstrated effectiveness in
treating disorders such as social anxiety, obsessive-compulsive disorder, premenstrual dysphoria
and panic as well as bulimia nervosa. In recent years, atypical antipsychotic drugs that have
come to market have been effective in treating schizophrenia and other psychotic disorders.
Coupled with increasing public awareness of mental health and often in conjunction with
psychological therapies, newer drugs have helped to encourage more people to seek pharmaceutical therapy for depression and other mental illnesses.
ACTIONS
APPENDIX A
The four examples above illustrate the increasing role of pharmaceuticals in treating a variety
of diseases. This evolution of disease treatment is portrayed in Figure 10. This role ranges from
direct treatment to prevention.
APPENDIX A
25 Fairman KA. The effect of new and continuing prescription drug use on cost: a longitudinal analysis of chronic and seasonal utilization. Clinical Therapeutics. 2000;22(5):641-652.
42
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
43
APPENDIX B
APPENDIX B
DRUG
IMPORTANCE
In contrast, prescription drugs have been and still are the only treatment modality available to
asthma patients (many nonprescription drugs are also used, as are allergy shots for patients with
allergic asthma). Before the introduction of asthma controller medications, people who suffered
from asthma were usually treated only after asthma attacks started. Preventive therapy consisted
mainly of avoiding risk factors — cold air, exercise and stress — thought to be responsible for
triggering attacks. Theophylline, discovered in the late 1890s but not used widely until the 1930s,
was the first “controller” in general medical use. It represented a new way to keep acute attacks
from sending people with asthma to emergency rooms or hospitals. Inhaled bronchodilators like
albuterol, which were first used during the 1960s, do a much better job of aborting acute attacks,
while inhaled corticosteroids — introduced in the following decade — and leukotriene receptor
antagonists — only available since the mid-1990s — serve to prevent asthma attacks. As the
prevalence of asthma grows, the number of people who use anti-asthmatic medications, and the
associated costs, will escalate.
During the past two centuries, science learned much about physical diseases and about mental
illnesses. Around the turn of the 20th century, psychological therapies began to be used. Sigmund
Freud popularized psychoanalysis; later other psychological treatments, such as behavioral,
humanistic and cognitive therapies became commonplace. By the 1930s, prefrontal lobotomy and
electroconvulsive shock were used to treat patients with schizophrenia and depression.
COST
FORECAST
COST
FORECAST
The treatment of GI diseases has also evolved dramatically over time. Until the availability of
H2 receptor antagonists in the 1970s and proton pump inhibitors (PPIs) in the 1990s, peptic
ulcer disease (PUD) was treated primarily with bland diets and surgery. Gastroesophageal reflux
disease (GERD), a disorder with symptoms similar to PUD, is treatable with drug therapy except
in rare, severe cases. GERD can be controlled with the same drugs used for ulcers, although longterm maintenance medications are usually necessary and some patients require higher doses for
adequate relief of symptoms. Over-the-counter (OTC) and prescription drugs used to treat GERD
and heartburn are heavily marketed through direct-to consumer (DTC) advertising. More money is
spent PMPY on prescription drugs to treat GI diseases than on any other class of drugs.
TRENDS IN
EXPENDITURES
DRUG
IMPORTANCE
GASTROINTESTINAL (GI) DISEASES
Although prescription drugs may replace other types of medical services, in some cases drugs
usually represent additive therapies. For example, few treatment options were available for people
who suffered heart attacks in the 1950s. Anyone who survived an initial heart attack was sent
home from the hospital with instructions to “take life easy” and little else. Twenty years later, cardiac pacemakers, open-heart surgeries, angioplasty and the first drugs to control blood pressure
had been developed for the treatment of heart attack survivors. By the end of the 20th century,
diagnostic procedures, like cardiac catheterization, and invasive therapies, like coronary artery
bypass surgery, were relatively commonplace — even among individuals who would not have been
considered for such heroic measures just a few years previously. In most cases, however, those
medical interventions must be followed by drug therapy to keep heart diseases under control.
INTRODUCTION
CARDIOVASCULAR DISEASES
PREFACE
ACTIONS
TABLE OF
CONTENTS
TABLE OF
CONTENTS
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TABLE OF
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TABLE OF
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22501_ii58
FIGURE 10
Disease
Earlier Treatment Type
Cardiovascular
lifestyle changes
2000 Typical Treatment Type
cardiac catheterization
cardiac pacemakers
coronary artery bypass surgery
open heart surgery
drug therapy
Asthma
theophylline
bronchodilators
avoiding risk factors
corticosteroids
PER MEMBER PER YEAR COVERED CHARGES FOR DRUGS AND OTHER MEDICAL SERVICES 1998-1999
(PERCENTAGE CHANGE)
$
leukotriene receptor antagonists
2000
Gastrointestinal
Mental Illness
diet
proton pump inhibitors
surgery
H2 receptor antagonists
psychoanalysis
psychoanalysis
psychological therapies
psychological therapies
prefrontal lobotomy
1,731
1998
1,592
1600
1999
1200
DRUG THERAPIES:
DRUG THERAPIES:
tricyclics
SSRIs
monoamine oxidase inhibitors
atypical antipsychotics
800
319 347
400
205 210
213 234
Office Visits
(2.5%)
Test/
Lab Path
(9.8%)
DRUG
IMPORTANCE
368 367
122 135
lithium carbonate
0
Total
(8.7%)
To further explore this changing relationship between drug and other medical care spending,
integrated medical and pharmacy claims data from Express Scripts’ subsidiary Practice Patterns
Science were analyzed. More specifically, claims data from 617,828 and 606,864 people who were
continuously eligible in calendar years 1998 and 1999, respectively, were examined. Primarily
consisting of HMO and PPO members, 51 percent of the members in these groups were females
and members had an average age of 33. For each of these populations, covered charges (charges
that were eligible for plan coverage before member financial contribution) were aggregated into
the following six categories of service:
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
Alternative
Sites &
Other
(10.6%)
To ascertain the degree to which these spending patterns held for members with particular
chronic diseases, the primary diagnosis was used to identify both the people with the following
diseases and the services used to treat them:
1. Hypertension
2. Peptic Ulcer Disease (PUD)
3. Gastroesophageal Reflux Disease (GERD)
4. Allergic Rhinitis
5. Asthma
6. Depression
For a member to be classified as having one of these six diseases, a diagnosis for that disease
must have been present sometime during the calendar year in question. To identify patients
with two other chronic conditions — diabetes and hyperlipidemia — either a diagnosis code or
a history of using specific drugs was employed. The drugs used to treat these specific diseases
are rarely used for other conditions.
45
APPENDIX B
44
Inpatient
Prof. &
Facility
(-0.4%)
APPENDIX A
1. Office visits
2. Tests/laboratory pathologies
3. Medical surgical/outpatient facility
4. Prescription drugs
5. Inpatient professional/facility
6. Alternative sites/all other services
Med Surg/
Prescription
Outpt Facility Drugs
(8.5%)
(20.3%)
ACTIONS
ACTIONS
438
DRUG
IMPORTANCE
APPENDIX A
364
COST
FORECAST
COST
FORECAST
electroconvulsive shock
INTEGRATED MEDICAL AND PHARMACY CLAIMS ANALYSIS
APPENDIX B
TRENDS IN
EXPENDITURES
TRENDS IN
EXPENDITURES
FIGURE 11
blood pressure medication
INTRODUCTION
INTRODUCTION
angioplasty
PREFACE
PREFACE
SUMMARY CHANGES IN TREATMENTS FOR SELECTED DISEASES
Expenditures for all medical conditions in total and for eight chronic conditions in particular
were analyzed in terms of PMPY costs. As is shown in Figure 11, consistent with the HCFA data,
prescription drugs charges increased at a faster rate than all other medical services. Between
1998 and 1999 charges for prescription drugs increased from 22.9 percent to 25.3 percent of
total charges PMPY. Put another way, of the $139 increase in total charges between 1998 and
1999, $74, or 53 percent of the total medical charge growth was attributable to increased
prescription drug costs.
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PREFACE
INTRODUCTION
TRENDS IN
EXPENDITURES
COST
FORECAST
TABLE 10:
In summary, analyses of integrated medical and pharmacy claims data support the argument
that, at least for some chronic diseases, prescription drugs account for a significant and growing
percentage of overall medical costs.
1998-1999 PERCENT CHANGE IN PER MEMBER PER YEAR COVERED CHARGES FOR DRUGS
AND OTHER MEDICAL SERVICES FOR SELECTED MEDICAL CONDITIONS
Medical Condition
Hypertension
Hyperlipidemia
Peptic Ulcer
Gastroesophageal Reflux
Rhinitis
Asthma
Diabetes
Depression
1998 Charges per Patient
1999 Charges per Patient
% Change
Other
Medical $
Drug $
Other
Medical $
Drug $
Other
Medical $ Drug $
$142
$76
$554
$238
$198
$205
$313
$649
$312
$338
$401
$470
$158
$339
$524
$629
$143
$76
$591
$267
$197
$220
$333
$498
$334
$378
$448
$503
$174
$388
$593
$697
1.1%
-0.4%
6.7%
12.1%
-0.2%
7.3%
6.4%
-23.3%
7.2%
11.7%
11.7%
7.2%
10.7%
14.3%
13.3%
10.8%
26 Adams PF, Hendershot GE, Marano MA. Table 57: Number of selected reported chronic conditions per 1,000 persons by
age. Current Estimates from the National Health Interview Survey, 1996. National Center for Health Statistics. Vital
Health Statistics. 10(200). 1999. p 81.
27 Nebel OT, Formes MF, Castell DO. Symptomatic gastroesophageal reflux: incidence and precipitating factors. American
Journal of Digestive Diseases. 1976;21:953-956.
28 Regier DA, Narrow WE, Rae DS, Manderscheid RW, Locke BZ, Goodwin FK. The de facto mental and addictive disorders
service system. Epidemiological Catchment Area prospective 1-year prevalence rates of disorders and services. Archives
of General Psychiatry. 1993;50(2): 85-94.
29 Roe CM, Motheral BR, Teitelbaum F, Rich MW. Angiotensin-converting enzyme inhibitor compliance and dosing among
patients with heart failure. American Heart Journal. 1999;138:818-825.
30 Fairman KA., Course of antidepressant treatment, drug type, and prescriber’s specialty. Psychiatric Services.
1998;49:1180-1186.
47
APPENDIX B
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
By the same token, however, some patients may be receiving inadequate doses of their medicines.
This situation can be the result of a patient’s or a physician’s behavior. In terms of the former, a
person with asthma may not know the proper way of using an inhaler, thereby wasting some of
the medication. Other patients may not follow-up with testing to assure adequate responses to
prescribed drugs. In terms of the latter, a physician may inadvertently prescribe subtherapeutic
doses of the medication, despite the prescription guidelines that are available for many diseases.29
This issue may be more prevalent among general practitioners who must digest a plethora of
information on the numerous diseases they must treat as opposed to a specialist who can concentrate on a few diseases and treatments.30
APPENDIX A
46
The growing dependence on pharmaceuticals to treat many diseases does not imply that prescription drugs are always used appropriately. Some people take prescription drugs unnecessarily.
For example, although depressive symptoms should be treated regardless of cause, short-term
situational depression does not usually have to be treated with antidepressants. People who
overeat or who indulge spicy foods once in awhile do not have to take prescription drugs to
treat the resulting heartburn. Some people with high blood pressure or high cholesterol levels
can control their conditions with diet and exercise. Some people with asthma can prevent acute
asthma attacks and the subsequent use of inhaled beta agonists to counteract those attacks
by avoiding exposure to various allergens.
ACTIONS
Two of the most widely used drug classes include products that treat GI diseases and depression.
Yet, as indicated by diagnosis codes, the prevalence of PUD/GERD, the most predominant GI
diseases, and depression were relatively small, approximately 2.1 percent and 1.8 percent,
respectively, in 1999. This situation could be an artifact of either people having received a
diagnosis for these diseases before the time period of the study or people being treated for those
conditions without having a corresponding diagnosis recorded. To get a better indication
of the probable prevalence of these diseases, members who had diagnoses for these diseases or
who used medicines that primarily treat these same diseases were identified. When the drug
markers are used as a surrogate for diagnosis, the prevalence of PUD/GERD and depression
increase dramatically. The prevalence of PUD/GERD rises from 2.1 percent to 9.2 percent. This
prevalence rate compares with national estimates that 1.4% of the population have an active
ulcer26, and that about 10 percent of Americans suffer from heartburn daily. 27 The prevalence
of depression grows from 1.8 percent to 9.9 percent, about the same as the 9.5 percent
national prevalence rate.28 It should be noted that some patients with other types of mental
illnesses likely are using these antidepressive drugs.
APPROPRIATE USE OF PRESCRIPTION DRUGS
DRUG
IMPORTANCE
DRUG
IMPORTANCE
• Drugs account for an even higher percentage of total costs in at least some diseases. In the
case of this expanded definition of PUD/GERD, drugs account for about 85 percent of total
spending. For depression, drugs spending grew to 81.8 percent of total 1999 charges, causing
PMPY total expenditures for depression treatment to go from negative 6.5 percent to a positive
0.6 percent compared to 1998 levels
COST
FORECAST
ACTIONS
• It is possible that diagnoses are not being properly recorded for a variety of reasons — to avoid
the stigma attached to a diagnosis of depression, for instance
TRENDS IN
EXPENDITURES
APPENDIX A
The implications of these findings are twofold:
INTRODUCTION
These eight medical conditions were selected for analysis because drugs used to treat them are
major contributors to overall drug costs. (See Table 10) Charges for prescription drugs ranged
from a low of 42 percent for PUD in 1998 to a high of 83.3 percent for hyperlipidemia in 1999.
Between 1998 and 1999, the proportion of total spending attributable to drugs rose for each of
these diseases except for GERD, which decreased slightly. Finally, charges for prescription drugs
account for one-half to the entire amount of the total expenditure growth for each of these diseases. Also noteworthy is that, with the exception of depression, which declined by 6.5 percent,
total PMPY covered charges associated with the treatment of these diseases increased from
4.6 percent for allergic rhinitis to 11.7 percent for asthma.
PREFACE
APPENDIX B
TABLE OF
CONTENTS
TABLE OF
CONTENTS
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PREFACE
LENGTH OF TREATMENT WITH ANY PRESCRIPTION IN SELECTED THERAPY CLASSES
90
80
60
90
180
270
360
450
540
630
720
Beta Blockers
Antipsychotics
Antihyperlipidemics
Anticonvulsants
Antihypertensives
Diuretics
Estrogens
Calcium Blockers
Antidiabetic
31 Phillips DP, Christenfeld N, Glynn, LM. Increase in US medication-error deaths between 1983 and 1993. The Lancet.
1998;351(9103):643-644.
32 Roe, CM. Have you been taking your medication? Proceedings of the 1999 Express Scripts Outcomes Conference; 1999
June, St. Louis, Missouri.
48
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
49
APPENDIX B
APPENDIX B
Optimizing the Benefits of Medication Use: In what are often referred to as utilization review
programs, patient populations that have been prescribed specific agents are screened for appropriateness to generally accepted medical guidelines. Physicians who routinely prescribe outside
guidelines may be offered information through one-on-one verbal interventions or use of printed
media targeting specific patients under their care. This information in intended not only to educate physicians about those specific patients, but also to improve prescribing in the future.
APPENDIX A
APPENDIX A
Antiasthmatics
In addition to concurrent DUR, Express Scripts offers a number of complimentary retrospective
clinical programs designed to promote appropriate drug use. Communications with physicians
and members for disease management and retrospective DUR programs will be greatly enhanced
by the availability of the Internet. Some of these programs are described below.
ACTIONS
ACTIONS
Days Since Initial Prescription
DRUG
IMPORTANCE
DRUG
IMPORTANCE
70
COST
FORECAST
COST
FORECAST
%
100
0
The appropriate use of legend drugs starts with the physician writing a prescription for the correct
drug in the right dosage form. For this to occur, the physician needs to be familiar with the array
of drugs that may be used to treat a particular disease, professional guidelines describing the
appropriate sequence and dosage of those drugs, drugs on the plan’s formulary, and other drugs
that patient is taking that may counteract or interact with the drug being prescribed. Once the
physician writes the prescription, the pharmacist must be able to read it and fill it correctly.
There are a number of tactics that can be employed to address these issues.
Most PBMs offer concurrent drug utilization review (DUR) programs. These programs consist of a
number of clinical edits designed to ensure that the appropriate drug is dispensed in the correct
dose to the suitable patient. To function correctly, concurrent DUR systems require access to
a patient’s eligibility and claims history. While the claim is being adjudicated real-time by the
pharmacy and PBM, a prescribed medication is edited for such things as appropriateness for a
gender, age group, disease, dosage, possible interactions with another medication the patient
is taking and formulary status. When these edits raise any of these concerns, a client can choose
to implement a hard block — meaning that the prescription cannot be adjudicated without an
override — or a soft-block that merely informs the pharmacy of a potential issue and relies on
the pharmacy to intercede with the physician if it chooses to do so. Most clients choose to
implement these edits via soft-blocks that minimize member disruption.
FIGURE 12
50
APPROACHES TO PROMOTING APPROPRIATE DRUG UTILIZATION
TRENDS IN
EXPENDITURES
In fact, most patients do receive the proper medication at the appropriate dosage levels. A more
important issue is whether the patient adheres to the treatment regimen — those with chronic
diseases need to take their medications exactly as prescribed. Figure 12 depicts a survival curve
showing the probability that continuously eligible members who used at least one drug in one of
10 chronic therapy classes stayed on a drug in that therapy class over a 24 month period (calendar
years 1997-1998). These data indicate that compliance decreases with time and varies with therapy
class. The probability of continuation for antidiabetic therapy was 95 percent and for antiasthmatic
therapy 82 percent at six months. The probabilities of continuation decreased to 92 percent for
antidiabetics and to 75 percent for antiasthmatics at one year. At two years, the probability of
continuing antidiabetics was 81 percent and the probability of continuing antiasthmatic therapy
was 51 percent.32
These data suggest that although there is variability in compliance rates across therapy classes,
there is room for improvement. Drug therapy cannot be effective unless patients take their medications appropriately. Improving compliance undoubtedly increases drug costs at the same time
that it enhances quality of care. From a different perspective, not only may noncompliance with
drug therapy jeopardize quality of care and, perhaps, health outcomes, it also results in wasted
resources. Paying for prescriptions that are not used properly is just the initial cost in a series of
potentially negative consequences that may result.
INTRODUCTION
INTRODUCTION
Most people assume that translating the physician’s hand-written prescription into the delivery
of the medication in the correct strength and dose to the patient is done correctly 100 percent of
the time. Unfortunately, this is not always the case. A recent report by the Institute of Medicine
indicated that errors involving prescription drugs kill more than 7,000 Americans a year.31
PREFACE
TRENDS IN
EXPENDITURES
TABLE OF
CONTENTS
TABLE OF
CONTENTS
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APPENDIX B
APPENDIX A
ACTIONS
DRUG
IMPORTANCE
COST
FORECAST
TRENDS IN
EXPENDITURES
INTRODUCTION
PREFACE
TABLE OF
CONTENTS
22501_ii58
Additional Pharmacological Intervention: Through retrospective targeting programs, patients
whose diseases could be better treated through the addition of medications to their treatment regimens can be identified. For instance, as discussed above, many new medications for the prevention of acute exacerbations of asthma are available. Patients receiving medications to treat exacerbations, or attacks, can benefit from the addition of controller medications, potentially decreasing
costs for avoidable physician office and emergency room visits. Many other examples point to the
importance of using databases organized across practice sites to better coordinate care.
Adhering to the Pharmacological Regimen: To benefit from an appropriately prescribed therapy,
the patient must continue to take the medication. As discussed earlier, patient compliance with
drug regimens often is less than optimal. Express Scripts has developed programs that help
patients remember to refill prescriptions, that provide access to professionals who can answer
questions or alleviate concerns about their drug therapy and that make the medication refill
process easy to use.
Disease Management: Another strategy to encourage appropriate prescription drug use is disease
management, an approach that encompasses the comprehensive management of a patient with a
specific disease. Programs range from identifying patients who have a given disease and sending
them objective educational materials to actively intervening, contacting and monitoring patients on
a regular basis. The latter strategy necessitates not only the availability of data to identify patients
with those diseases, but also the mechanisms to intervene.
Use of Preferred Products: The availability of many products with similar therapeutic profiles
within distinct therapeutic drug classes allows flexibility in selection of preferred agents that can
decrease costs and obtain equal or superior clinical efficacy. Adding formulary benefit designs
that incentivize physicians and patients to select preferred products is a rational approach.
Electronic Prescribing: Neither the concurrent nor the retrospective DUR programs involve
real-time communications with a physician, a situation that reduces the effectiveness of many
such programs. This reality has particular importance at the points that a physician prescribes
a product and that prescription is filled with the medication the pharmacist thinks was written
by the physician. A strategy to ameliorate this problem is to link the physician, PBM and pharmacy
real-time in the prescribing and dispensing processes. This approach — enabled by standardized
communication protocols and electronic prescribing technology — puts all of the patient’s
pharmacy claims history and plan sponsor’s coverage rules in the hands of the physician as the
prescription is written. This information allows the physician to act immediately on any concurrent
clinical edits, formulary concerns or coverage issues that may be triggered before the prescription
is sent to the pharmacy. In addition, the prescription is sent electronically to the pharmacy of
the member’s choosing to be filled. The electronic transmission of the prescription avoids misfills
due to problems reading handwritten prescriptions. The communication channel also provides a
vehicle for the PBM, in concert with the plan sponsor, to communicate with the physician on any
possible issues related to prescribing guidelines, polypharmacy, patient compliance issues or
other matters related to retrospective DUR programs.
50
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
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A C T I O N S T O M I T I G AT E I M PA C T O F C O S T T R E N D
APPENDIX A
Managing drug choices within a therapeutic class has become a viable alternative for reducing
costs. Compared with the more indirect approach of physician intervention and behavior changes,
ACTIONS
Limiting the number of pills that a member can receive for one copay can control excessive
quantities per prescription. Such a quantity limit program involves targeting products for which
prescriptions are prone to include quantities beyond what is suggested for typical use. Depending
on how aggressive the client is willing to be, a quantity limits program can save between
$0.10 and $0.20 per member per month.
DRUG
IMPORTANCE
The plan sponsor can directly affect the per-prescription cost by controlling or influencing the
mix of products reimbursable under the drug plan benefit. In a mandatory generic program,
the member is required to pay the difference in price between a multi-source brand for which a
generic is available and the generic equivalent. A mandatory generic program can be implemented
in a way that requires the member to pay the difference only if the physician has indicated that
a generic can be substituted or regardless of whether the physician had indicated that a generic
could be substituted. In 2000, 86 percent of Express Scripts’ HMO clients had a mandatory generic
program. In contrast, 51 percent of non-managed care commercial clients had such a program.
COST
FORECAST
The deepest discounts that payers generally can attain are through a mail service pharmacy, which
can lower costs by capitalizing on economies of scale. Consequently, when member copayments
are set appropriately, it is beneficial for the payer to encourage members to have prescriptions
that are used to treat chronic diseases filled through mail service. About 87 percent of large
employers have a mail service benefit.33 On the retail side of the equation, better discounts can
be obtained by driving higher volume into network stores. Thus, a payer willing to limit the
number of retail pharmacies in its network can obtain deeper discounts.
TRENDS IN
EXPENDITURES
Payers can reduce per-prescription costs by adopting particular ground rules under which they
will pay for drug products. They can limit the size of retail networks; promote the use of mail
service; and implement programs for mandatory generics, quantity limits, step therapy and
therapeutic switching.
INTRODUCTION
ACTIONS AIMED AT CONTROLLING PER-PRESCRIPTION COSTS
PREFACE
The confluence of the factors described above has placed plan sponsors in the dilemma of paying
for ever increasing pharmacy costs, a situation that is compounded by the downturn in the economy.
In addition to the clinical interventions discussed in the preceding section, a number of strategies
can be employed to offset rising drug costs. These techniques include actions aimed at controlling
per-prescription drug costs, reducing utilization of prescription drugs and reducing both prescription costs and utilization, as well as implementing defined contribution programs that include
member choice.
33 Wyeth-Ayerst Prescription Drug Benefit Cost and Plan Design Survey Report, 2000 Edition. Albuquerque: Wellman
Publishing, Inc. 2000.
APPENDIX B
51
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PREFACE
INTRODUCTION
FIGURE 13
INCREASES IN AVERAGE PRESCRIPTION COST FROM 1996 TO 2000 BY THERAPY CLASS
84.62
58.64
Antidepressants
77.51
Anti-Rheumatics (NSAIDS)
43.53
Antihypertensives
42.54
36.07
60.24
Antidiabetics
31.99
58.25
44.78
Antihistamines
52.59
Antiasthmatics
35.04
57.28
50.18
49.40
Calcium Blockers
Dermatologicals
31.57
30.09
16.02
Narcotic Analgesics
190.09
Antivirals
122.06
28.83
17.64
32.87
26.08
Cough/Cold
Oral Contraceptives
76.45
Anticonvulsants
46.85
33.90
28.58
Beta Blockers
241.87
APPENDIX A
APPENDIX B
52 EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
Macrolides
42.59
Antianxiety Agents
25.79
Penicillins
25.56
14.56
138.19
Migraine Products
85.12
50.73
44.97
Cephalosporins
110.19
Misc. Endocrine
128.25
51.25
36.09
Decongestants
38.77
24.19
Other
52.39
Total
$
34.68
0
50
100
150
200
250
53
APPENDIX B
Member cost share directly affects the cost of every prescription covered by plan sponsors. Every
dollar the member pays for a drug is a dollar the payer does not have to pay. Despite this fact,
many plan sponsors do not regularly adjust their member cost share structure. The effects of
43.25
35.64
APPENDIX A
Persons who view prescription drugs as a virtually free good to which they are entitled have little or no
incentive to worry about the cost of that drug. Consequently, one critical challenge facing the payer
is to sensitize participants/members to drug costs. The most direct way of accomplishing this goal
is to make the member financially responsible for part of the cost of the medications consumed.
Members who are not cost-sensitive have no reason to think about whether they really need the prescription. Neither do they consider the number of units of the drug needed vs. how many might be
used or whether a less expensive drug will yield the same clinical outcome as a more costly agent.
168.36
ACTIONS
ACTIONS
Antineoplastics
REDUCING PER-PRESCRIPTION COSTS AND UTILIZATION
DRUG
IMPORTANCE
26.07
17.52
Estrogens
Other types of initiatives can be adopted to assist payers that have a closed panel of physicians.
Some plans have put physicians at risk for prescription drug costs, while others have incorporated
financial incentives for physicians to better manage prescription drug costs. Challenges to
including drugs in capitation and risk pools have emerged in some states through litigation
and proposed legislation to prohibit or modify these reimbursement techniques.
1996
86.84
76.08
72.23
Antihyperlipidemics
COST
FORECAST
A number of strategies can be employed to reduce utilization in a responsible manner. One
approach is simply to exclude prescription cosmetics and other lifestyle drugs. Most plans do
exclude a variety of such products, but given the number of lifestyle products that continually
come to market, the list of excluded products must be continually re-evaluated. Concurrent drug
utilization review (DUR) programs include online edits for duplicate therapies, drug interactions,
too-early refills and the like. Another concurrent program aimed at reducing unnecessary utilization is prior authorization. Prior authorization programs require a patient be a given age or have
a documented diagnosis to receive a prescription for a specific drug. Retrospective DUR programs
also can be implemented. Such programs are designed to identify issues pertaining to polypharmacy, drugs of concern for specific age groups and questionable use of controlled substances.
2000
116.37
Gastrointestinals
REDUCING UTILIZATION OF PRESCRIPTION DRUGS
TRENDS IN
EXPENDITURES
TRENDS IN
EXPENDITURES
Therapeutic switching is another vehicle that can be used to reduce per-prescription costs. Most
formulary lists designate specified products as preferred — products that are at least as efficacious
as non-preferred drugs but that have the potential to provide the greatest level of net savings for
the plan. These programs encourage physicians and members to switch from more expensive
products to less costly but still therapeutically equivalent products. As connectivity between the
PBM and the physician’s office becomes more widespread, real-time implementation regarding
formulary compliance and concurrent plan design edits will become a more effective and less
cumbersome method of implementing plan sponsor programs.
holding member cost share constant can be dramatic. The average AWP cost per prescription
grew by 51.1 percent between 1996 and 2000. As is shown in Figure 13, average per-prescription
costs rose for all but one — miscellaneous endocrines — of the top 25 therapy classes. These
increases ranged from 12.8 percent for cephalosporins to 88.3 percent for antidiabetics. Payers
that had static member cost share levels during this period had to bear the entire burden of these
increases. Between 1995 and 1998, member share of cost for clients in this report actually declined
from 21.8 percent in 1995 to 20.3 percent in 1998. As payers have increased copays in the last
couple of years, member share of cost grew to 21 percent in 1999 and to 22.4 percent in 2000.
This pattern is evident among both HMO and commercial clients. However, in all years, member
share of cost is higher for HMO clients than for commercial clients.
INTRODUCTION
COST
FORECAST
plans are opting to manage utilization choices at the point of service. Requiring the plan participant to try the most cost effective drug therapy, such as a generic, for a particular condition before
the plan will pay for a more-advanced, and generally more-expensive drug, can potentially reduce
the cost of treatment. This strategy, often referred to as step therapy, is especially successful for
short-term drug therapies.
PREFACE
DRUG
IMPORTANCE
TABLE OF
CONTENTS
TABLE OF
CONTENTS
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APPENDIX B
55
PREFACE
INTRODUCTION
TRENDS IN
EXPENDITURES
COST
FORECAST
DRUG
IMPORTANCE
ACTIONS
APPENDIX A
APPENDIX A
54 EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
34 Scott-Levin. 2000 Managed Care Formulary Drug Audit.
35 Roe. 1999.
36 Fairman KA, Motheral BR, Teitelbaum F. One size fits most: commercially insured enrollees respond to a three-tier drug
copayment. Presented at: Managing the Pharmacy Benefit. 1999 January. Tucson, Arizona.
ACTIONS
A three-tier copay plan has become more attractive to payers because the plan sponsor still pays
for the drug, albeit a lesser amount, making it perhaps more marketable than a closed formulary.
Depending on the number of drugs placed on the third tier, a plan moving from a $5/$10 copay
The classes bolded in Figure 14 — gastrointestinals, antihypertensives, antianxiety agents and
antihistamines — appear poised to make significant moves toward high generic cost and high
generic fill rate status in the next couple of years. Each class has a current popular brand
DRUG
IMPORTANCE
Some clients have initiated or are contemplating a four-tier copay system. This approach essentially
is a variant of a closed formulary in that the member must pay 100 percent of the costs for some
drugs. As in a three-tier system, there are three escalating copay amounts for generics, preferred
brands and non-preferred brands. However, specific types of drugs are placed on a fourth tier.
The member is responsible for paying the total cost of all these fourth-tier products. The plan
does not exclude drugs from coverage; rather, all drugs are accessible but the member copay
varies according to which drugs the member chooses. The advantage to members is that they
benefit from the negotiated discounts for the tier-four products. Another variation of a four-tier
copay system is to cover these fourth-tier drugs but charge the member a substantial copay,
50 percent-75 percent, of the cost of these products.
In the same way that payers are adopting copay structures with non-preferred brands on a third
tier, so too can they adopt benefit designs to address the disparity in the costs of generic drugs
across therapy classes. Such plan designs, however, need to be carefully thought out so as to
maximize the savings realized by the payer. Figure 14 shows that the classes with low cost
generics and high generic fill rates are classes that have not had any significant brands lose
patent protection in recent years. Conversely, some of the classes with higher cost generics have
had popular brands recently go generic. None of these classes currently lie in the upper right
quadrant in Figure 14 where high priced generics are coupled with a high generic fill rate.
COST
FORECAST
In the recent past, few payers adopted closed formularies that exclude significant numbers of
branded drugs from coverage. As consumers have increasingly demanded access to all drugs,
even fewer payers have chosen this approach. To the contrary, more plans that had closed formularies are moving to less restrictive approaches. One such approach is a three-tier copay
plan. Under this scenario, a member’s copay is lowest for generics (tier one), somewhat higher
for preferred or neutral brands (tier two) and highest for expensive and non-preferred branded
products (tier three). Members desiring tier-three products are not denied access to them as
part of the covered benefit but instead are charged a premium, in the form of a higher copay,
for using those products. This type of plan helps the payer either by inducing the member to use
less expensive brands (tier-two drugs) or generics (tier-one drugs) or by allowing the payer to
reduce costs for tier-three drugs through higher member copays.
Three-tier and four-tier copay plans usually focus on whether branded products should be placed
on the second, third or fourth copay tier. Much less thought or attention is paid to generic copays.
For many years, generic copays were set at very low amounts to encourage use of these products.
This strategy was premised on the fact that generics were not only less expensive than branded
products, but also were inexpensive in absolute terms. Until very recently, this strategy was sound.
Now, however, not all generics are as inexpensive as others. The average AWP cost for generics in
classes such as antidepressants, narcotic analgesics, estrogens, cough/cold, penicillins, corticosteroids and diuretics ranges from $2.28 to $25 (see Figure 14). However, the generic versions of
many of the brands that recently have come off patent are more expensive than generics in the
aforementioned classes. For example, led by an average prescription cost of $88 for ranitidine
(generic Zantac®), the average generic prescription cost in the GI class was $65 in 2000. Relatively
high average AWP per prescription costs are also evident for generics in the antihypertensive,
oral antidiabetic, calcium blocker and anticonvulsant classes. These relatively high costs are
compounded by the recent large price increases seen for some generic products.
TRENDS IN
EXPENDITURES
Express Scripts clients, like other payers nationwide, have raised 2000 copay levels more aggressively than in the past, particularly for branded products. In the aggregate, between 1997 and
2000, MCO and commercial clients raised network copays for generics from $5.57 to $7.54 and
copays for brands from $10.91 to $15.31. MCO clients raised copays more than their commercial
counterparts. Between 1999 and 2000, MCO copays went from $7.06 to $7.89 for generics and
from $14.84 to $16.50 for brands. Commercial clients raised their generic copays from $6.73 to
$6.90 and branded copays from $12.20 to $13.08.
structure to a three-tier plan at $5/$10/$25 can save between 5 percent and 8 percent of its overall drug cost. The percentage of MCOs offering a three-tier copay structure rose from 36 percent
in the spring of 1998 to 80 percent by the spring of 2000.34 The number of members enrolled in
three-tier copay plans rose from 9 percent to 35 percent in this same period. According to the
Scott-Levin findings, in 2000 the average three-tier copayment was $7.06 for generics, $14.30
for formulary branded drugs and $29.01 for non-formulary drugs. For clients choosing a threetier copay approach, care should be taken not to set the third-tier copay level so high as to
dissuade members from having essential prescriptions filled or refilled, a situation that could
result in emergency room or inpatient admissions.35 Thus, the levels at which copays are set
must take into account the family income of the covered membership and the types of drugs
placed on the third tier.36
INTRODUCTION
The member share of cost generally takes the form of a front-end deductible, a copay for every
prescription dispensed or a limitation on the total amount of drug costs for which the plan
sponsor will pay over a year. Very few clients have a front-end deductible — only about 7 percent
of commercial clients and less than 1 percent of HMOs. That so few clients have a deductible is
not surprising. A deductible is not member friendly in that it affects all members who use the drug
benefit. Deductibles also place more of a hardship on patients who potentially must pay the full
cost of a prescription instead of a much smaller copay amount. This larger payment may keep a
patient from receiving a discretionary (lifestyle/cosmetic) medicine, but it also potentially deters
that patient from getting a more needed medication. For the few commercial clients that did have
a deductible plan, the average deductible is $82 for an individual and $174 for a family.
PREFACE
APPENDIX B
TABLE OF
CONTENTS
TABLE OF
CONTENTS
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PREFACE
INTRODUCTION
An additional opportunity to reduce cost and utilization is by augmenting a mandatory generic
program with a closed formulary, which limits the single-source drugs for which the plan sponsor
will pay. A payer can choose to exclude from coverage more expensive branded products for which
less costly therapeutic alternatives are available. An even more aggressive strategy is to deny
coverage for entire classes of drugs, such as those to treat baldness or obesity. A payer adopting
a closed formulary must have medical override protocols to deal with instances in which the
physician determines that a patient must have the non-covered drug. The amount of saving from
this strategy is directly related to the degree of restrictiveness of the formulary.
To deal with changing cost of generic products, payers should consider instituting higher copays
for generics that cost more than a set amount. For example, a copay of $15 could be levied for
any generic product that costs more than $15. A copay of, for instance, $3 could apply to generic
products that cost less than $15. This type of two-tier generic copay can be combined with a
preferred brand/non-preferred brand copay structure to form a four-tier copay.
DEFINED BENEFIT CONTRIBUTION AND MEMBER CHOICE
$70
Gastrointestinals
Antihyperlipidemics
Calcium Blockers
$50
Oral Antidiabetics
Antihypertensives
$40
Anticonvulsants
$30
Macrolides
Anti-Rheumatics (NSAIDS)
Antiasthmatics
Oral Contraceptives
Antidepressants
Cephalosporins
Migraine Products
Estrogens
Antihistimines
Narcotic Analgesics
Diuretics
Penicillins
Thyroid
Corticosteroids
$0
0%
20 %
40 %
60 %
80%
100%
56 EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
57
APPENDIX B
38 Levitt L, Holve E, Wang J, Gaebel JR, Whitmore HH, Pickreign JD, Miller N, Hawkins S. Employer Health Benefits. 2000
Annual Survey. Menlo Park, California: The Kaiser Family Foundation and Chicago: The Health Research and Educational
Trust. 2000.
APPENDIX A
Another approach that payers can adopt to keep pace with increases in the average cost per prescription is co-insurance — a percentage member copay. Clients that adopt co-insurance do not
have to worry about inflation creep because the member automatically assumes a constant percentage of per-prescription cost increase. Only 3 percent to 4 percent of HMO, PPO and indemnity
clients have co-insurance plans,38 because co-insurance is not member friendly. That is, because
the member pays a percentage of the cost of a prescription and the cost of most medicines
changes once or twice a year, the member never knows how much she will have to pay for that
prescription at any point in time.
A second way that defined contribution can be operationalized is similar to the first in two ways:
the employer fixes the level of contribution it will provide; and the member has a choice. However,
instead of handing over the amount to the employee and expecting the individual to purchase
coverage, the employer negotiates with various insurers for different coverage packages. These
packages offer more coverage at higher rates or less coverage at lower cost. The employee then
chooses which of these packages to purchase and pays the difference between the premium and
the amount of the employer’s contribution. This approach still fixes the employer’s cost and gives
the employee choice, but it has the advantage of leveraging a large number of lives to negotiate
better insurance rates. It also takes the burden off of the employee to identify and analyze the
various insurance packages that are marketed and determine which is best for his or her family.
This is the approach that is extant for federal employees.
ACTIONS
ACTIONS
$10
DRUG
IMPORTANCE
DRUG
IMPORTANCE
Cough/Cold
APPENDIX A
Antianxiety Agents
Dermatologicals
$20
APPENDIX B
Beta Blockers
COST
FORECAST
COST
FORECAST
$60
TRENDS IN
EXPENDITURES
FIGURE 14
GENERIC FILL RATE AND GENERIC AWP PER PRESCRIPTION FOR SELECTED THERAPY CLASSES 2000
Defined contribution is a term that means somewhat different things to different people.
Generally, defined contribution implies that the employer provides a fixed amount of money to
purchase an employee’s healthcare coverage. One form of this strategy is that the employer literally hands over this fixed employer payment directly to the employee. In theory, the amount of the
employer’s contribution is an actuarially derived amount predicated on the level of insurance the
employer determines is appropriate, as well as on the percentage of that cost the employer thinks
it should pay. In turn, it is the employee’s responsibility to determine what health coverage packages
are available and which packages are appropriate for him/her, and then to pay for the coverage
selected. If the coverage is less than the employer’s payment, the employee pockets the excess
employer contribution. If the coverage premium is higher than the employer’s contribution, the
employee must pay the difference. The richer the coverage the employee desires, the higher the
premium and therefore the greater the employee’s share of that premium. Although it caps the
employer’s financial exposure, this strategy places the employee in the difficult position of having
to purchase health insurance without the leverage of numbers enjoyed by an employer who is
negotiating rates for many lives. Without a government-mandated set of coverages, risk-pooling
plans and regulation of premiums, the employee may be unable to find affordable health insurance with adequate coverage. Alternatively, if enough employers adopt this tactic, the medical
provider/insurance industry may fill this need. If so, government likely would have to regulate
these providers to ensure their financial viability as well as the quality of care they deliver.
INTRODUCTION
due to go off patent soon — Prilosec® in the gastrointestinal, Prozac® in the antidepressant,
Prinivil®/Zestril® in the antihypertensive, BuSpar® in the antianxiety and Claritin® in the antimistamine classes, respectively. With the exception of antihistamines, in each of these classes, generics
have already been increasing at rates greater than the rate of all generics combined. As the
average generic prescription cost rises in some therapy classes, the logic of varying generic
copays becomes more compelling. Indeed, unless generic copays are raised for some generic
products relatively soon, it will be very difficult for plan sponsors to attain or maintain a desired
level of member cost share.
PREFACE
TRENDS IN
EXPENDITURES
TABLE OF
CONTENTS
TABLE OF
CONTENTS
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This latter strategy can be applied in a carved-out pharmacy benefit context. The employer offers
its workers multiple coverage options but caps the employer contribution at a set amount. This
approach responds to consumer choice at the same time that it ties pharmacy use more directly
to member financial responsibility. For example, an employer could provide one package for all
drugs, regardless of the type of condition the drug treats and another that excludes coverage of
drugs for which there are less expensive alternatives and for drugs used for cosmetic purposes.
In either case, the employer will contribute the same amount of money. The employee selecting
the richer benefit that includes all drugs or drugs that treat cosmetic conditions pays the incremental costs attached to the coverage of these drugs. This approach provides the employee open
access to all drugs, but places part of the financial burden on the employee for his or her choices.
One important consideration that must be taken into account when adopting this strategy is
whether to maintain some element of insurance in the pricing decision. A key assumption in
insurance is that the price of the benefit should be spread across both the healthy and sick or,
put another way, between low and high utilizers. This principle entails low utilizers subsidizing
the costs of high utilizers.
Regardless of the method employed, payers have been and will continue to pass along to patients
an ever-growing financial responsibility for the prescription drugs consumers take for granted as
being readily accessible and inexpensive. Depending on how the financial shift is accomplished,
those who can least financially afford to pay this extra amount might be forced to do without
much-needed medications. Consequently, payers must carefully consider the demographic makeup of their employee and dependent populations, as well as the types of drugs that may be placed
on a third tier.
APPENDIX B
APPENDIX A
ACTIONS
DRUG
IMPORTANCE
COST
FORECAST
TRENDS IN
EXPENDITURES
INTRODUCTION
PREFACE
TABLE OF
CONTENTS
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58 EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
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TABLE OF
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A
a ppendix
PREFACE
TRENDS IN
EXPENDITURES
COST
FORECAST
DRUG
IMPORTANCE
ACTIONS
APPENDIX A
APPENDIX B
59
INTRODUCTION
Dr ug Therapy
Class Revie w
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DRUG THERAPY CLASS REVIEW
GASTROINTESTINALS
In 2000, the top 25 therapy classes accounted for more than 80 percent of total AWP prescription
costs. The data in this Appendix depict the cost and utilization trends for these classes from
1996 through 2000. The discussion of these therapy classes primarily addresses the changes
that occurred between 1999 and 2000. Drugs that are now in the pipeline that may significantly
impact these classes over the next several years are also discussed. The data included in these
analyses include all drugs, both common and new.
Among the most common gastrointestinal (GI) conditions are peptic ulcer disease (PUD) and
gastroesophageal reflux disease (GERD). As research uncovers new compounds, drugs to treat
less common GI complaints such as chronic constipation, irritable bowel syndrome (IBS) and
inflammatory bowel disease are beginning to be developed. For example, Colazal® (balsalazide)
was approved in 2000 for the treatment of ulcerative colitis — an inflammatory condition of
the colon.
PREFACE
PREFACE
6/4/01
TABLE OF
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TABLE OF
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TRENDS IN
EXPENDITURES
COST
FORECAST
DRUG
IMPORTANCE
%
CHANGE
1999
$ PMPY
2000
$ PMPY
%
CHANGE
Gastrointestinals
Antidepressants
Antihyperlipidemics
Anti-Rheum (NSAIDS)
Antihypertensives
Antidiabetics
Antihistamines
Antiasthmatics
Calcium Blockers
Dermatologicals
Narcotic Analgesics
Estrogens
Antivirals
Cough/Cold
Oral Contraceptives
Anticonvulsants
Beta Blockers
Anticancer
Macrolides
Antianxiety Agents
Penicillins
Migraine Products
Cephalosporins
Misc. Endocrine
Decongestants
Other
$106.60
$72.55
$82.37
$58.90
$39.96
$51.57
$54.48
$46.96
$54.79
$42.94
$24.48
$22.59
$194.25
$24.64
$31.17
$66.73
$31.68
$226.03
$40.90
$39.18
$22.26
$124.28
$49.64
$110.71
$47.03
$34.38
$116.37
$77.51
$86.84
$72.23
$42.54
$60.24
$58.25
$52.59
$57.28
$49.40
$30.09
$26.07
$190.09
$28.83
$32.87
$76.45
$33.90
$241.87
$43.25
$42.59
$25.56
$138.19
$50.73
$110.19
$51.25
$38.77
9.2%
6.8%
5.4%
22.6%
6.4%
16.8%
6.9%
12.0%
4.5%
15.1%
22.9%
15.4%
-2.1%
17.0%
5.4%
14.6%
7.0%
7.0%
5.7%
8.7%
14.8%
11.2%
2.2%
-0.5%
9.0%
12.8%
$34.23
$33.68
$26.17
$17.93
$20.37
$14.82
$13.96
$13.67
$13.77
$11.79
$9.24
$9.59
$10.29
$9.03
$9.18
$7.13
$7.70
$7.10
$8.18
$6.96
$6.78
$6.40
$7.65
$5.31
$6.38
$69.79
$40.53
$39.55
$32.28
$24.72
$23.74
$18.66
$15.95
$15.40
$14.11
$13.36
$12.46
$10.79
$10.02
$9.54
$9.34
$9.26
$8.91
$8.54
$8.01
$8.01
$7.39
$7.09
$6.94
$6.89
$6.85
$81.39
18.4%
17.4%
23.4%
37.9%
16.6%
25.9%
14.3%
12.7%
2.5%
13.3%
34.8%
12.4%
-2.6%
5.6%
1.7%
29.9%
15.7%
20.4%
-2.1%
15.1%
8.9%
10.9%
-9.4%
29.8%
7.4%
16.6%
$46.77
$52.39
12.0%
$387.09
$449.74
16.2%
Total
GERD, a disorder with symptoms similar to PUD, is caused by a loosening of the pyloric sphincter
— a muscular gate between the esophagus and the stomach. Normally closed, the sphincter
sometimes relaxes inappropriately, allowing stomach acid to back up into the esophagus.
Heartburn, chest pain, cough, swallowing difficulties and a sour taste can all result. Most people
experience heartburn only occasionally, but millions of Americans suffer from frequent heartburn
— with more than half the cases occurring in people over the age of 45. Currently incurable,
GERD can be controlled with the same drugs used for ulcers, although drug therapy for GERD is
usually long term and the drug doses are higher.
If it is untreated, GERD can lead to more serious complications — including a condition known
as Barrett’s esophagus (BE). In about 8 percent to 10 percent of people who have GERD, damage
from stomach acid causes cells lining the esophagus to become more like the acid-resisting cells
in the stomach or small intestine. BE is considered to be a precancerous condition. Although treating
the underlying GERD may relieve symptoms, slow BE progression and help prevent complications, no
current treatments can reverse changes in esophageal cells.
No apparent cause can be determined for some people who experience frequent heartburn, nausea,
bloating or borborygmus — a rumbling stomach. They may have non-ulcer dyspepsia (NUD).
Thought to be related to activities like smoking, chewing gum, eating fatty or spicy foods and
drinking carbonated or alcoholic beverages, NUD also may be associated with depression or anxiety. It seems to be more prevalent during times of stress or fatigue. While treatment with the
same drugs used for PUD and GERD can relieve symptoms of NUD, it is likely to recur.
ACTIONS
2000
AWP/RX
DRUG
IMPORTANCE
1999
AWP/RX
COST
FORECAST
THERAPY CLASS
Until recently, few therapeutic options were available to treat PUD. Fortunately, one cause of
peptic ulcers was identified in the 1980s as a particular bacterium, Helicobacter pylori, that can
be eliminated through relatively simple treatment. Current therapy involves the combination of
an acid suppressor — either an H2 receptor antagonist (H2RA) or a Proton Pump Inhibitor (PPI)
— to control excess stomach acid production and two or more antibiotics to eliminate H. pylori.
A short course — usually 10 days to 14 days — is enough to kill the bacterium. This triple
therapy not only heals ulcers, it keeps them from coming back.
TRENDS IN
EXPENDITURES
ACTIONS
COST PER PRESCRIPTION AND PMPY COST FOR MAJOR THERAPY CLASSES 1999-2000
INTRODUCTION
INTRODUCTION
TABLE A1
▲▲▲▲
35+
▲▲▲
20-34
▲▲
10-19
▲
1-9
▼
LESS THAN 0
2000 average AWPs (representing average prescription cost) are reported following each drug name in
the legend for each Market Share Trend figure.
60
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
61
APPENDIX B
APPENDIX B
PERCENTAGE CHANGE IN PMPY COST FROM 1999-2000
APPENDIX A
APPENDIX A
MARKET SHARE TABLE LEGEND
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• Another PPI, Prevacid® was given additional indications both for healing gastric ulcers and for
reducing the risk of gastric ulcers associated with the use of NSAIDs.
FIGURE A1 THERAPY CLASS DRUG MARKET SHARE TREND
% CHANGE IN PMPY COST
18.4%
%
35
Zantac ($86.53)
30
Axid ($108.66)
25
Cimetidine ($83.08)
20
Pepcid ($103.57)
15
Ranitidine HCL ($88.09)
10
• In November 2000, Pepcid® Complete (famotidine, calcium carbonate and magnesium
hydroxide) was introduced to the OTC market. This new combination, consisting of an H2RA
with an antacid in a chewable tablet form, is to be taken twice a day. In the meantime, patent
protection has expired for Pepcid®. Both the oral and the injectable forms of famotidine, the
generic for Pepcid®, have been approved by the FDA.
INTRODUCTION
INTRODUCTION
• The fourth PPI to become available in the United States is Protonix®, which was launched in the
spring of 2000. Approved only for short-term treatment of esophagitis caused by GERD,
Protonix® is also being used off-label for PUD and for primary treatment of GERD.
2000PMPY = $40.53
PREFACE
PREFACE
GASTROINTESTINALS
Prilosec ($148.96)
• Less than a year after its approval for irritable bowel syndrome (IBS) in women, Lotronex® (alosetron) was withdrawn from the market due to concern over potentially dangerous side effects. It
was reportedly the cause of intestinal damage including severely obstructed or ruptured bowels.
Prevacid ($134.23)
0
1996
1997
1998
1999
2000
DRUG
IMPORTANCE
Future Trends
• In 2000 the AWP per prescription costs for Prilosec® and Prevacid® grew about 7 percent to
$148.96 and $134.23, respectively, compared to $88.09 for ranitidine. Along with an 8.5 percent increase in utilization for this class, the shift to the use of more expensive PPIs contributed
an over $6 PMPY cost increase in this class.
®
• Approval for Nexium (esomeprazole), was granted by the FDA in February 2001. Currently
the only second generation PPI available in the United States, Nexium® has indications for
relieving GERD symptoms, for healing erosive esophagitis, and for eliminating H. pylori when
taken in combination with amoxicillin and Biaxin® (clarithromycin). It is marketed by the same
company that sells Prilosec®.
• Helicide® (bismuth subcitrate, metronidazole and tetracycline) is finishing Phase III trials for
H. pylori treatment. By combining three medications into a single dose form, Helicide® intended
to simplify therapy. Another combination, Helidac® (bismuth subsalicylate, metronidazole and
tetracycline) is already on the U.S. market and a third one, Tritec® (ranitidine bismuth citrate),
was discontinued in 2000.
62
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
63
APPENDIX B
APPENDIX B
APPENDIX A
APPENDIX A
• Mosapride and norcisapride are gastric prokinetic agents that are being studied for heartburn,
nausea and other symptoms of chronic gastritis. Drugs in this class speed up gastric emptying
time, similar to the recently withdrawn Propulsid®.
ACTIONS
• Patent protection for Prilosec®, originally scheduled to expire as early as April 2001, will be
extended for six months while the manufacturer conducts studies in pediatric patients. Release
of a generic has been further delayed by lawsuits against potential generic suppliers. A request
for OTC status for Prilosec® was denied by the FDA.
• Zelmac® (tegaserod) is currently under review at the FDA, with final approval expected in 2001.
Likely to be approved for use in women with constipation-predominant IBS, Zelmac® is also
being studied for GERD.
DRUG
IMPORTANCE
ACTIONS
• The ascension of PPI market share continued in 2000. The market share for PPIs — Prilosec
(omeprazole) and Prevacid® (lansoprazole) and Protonix® (pantoprazole), which was introduced
in 2000 — grew from 46.4 percent in 1998 to 55.5 percent in 1999 to 60.3 percent in 2000.
• Another drug important in the treatment of GERD, Propulsid® (cisapride), was withdrawn from
the U.S. market in 2000. Continuing concerns about heart arrhythmias and drug interactions
associated with the use of Propulsid® lead to the withdrawal.
COST
FORECAST
COST
FORECAST
®
TRENDS IN
EXPENDITURES
TRENDS IN
EXPENDITURES
5
PREFACE
INTRODUCTION
Page 64
CENTRAL NERVOUS SYSTEM
As the population ages, more people will be affected by diseases that involve the neurological
system. Neurological conditions can result from injuries, from chemical imbalances, from physical
degeneration of the nervous system or from a combination of causes. They include conditions
like Alzheimer’s disease, Parkinson’s disease, narcolepsy, multiple sclerosis (MS), attention
deficit/hyperactivity disorder (ADHD), as well as depression, anxiety, epilepsy and psychoses.
Intensive research during the 1990s and new discoveries from the human genome project hold
promise for advances in treatment of many central nervous system (CNS) conditions.
Dementia is simply the deterioration of intellect, often associated with declines in emotional
and physical functioning. The most common cause of dementia is Alzheimer’s disease. Currently,
treatment for Alzheimer’s centers on relieving symptoms. It is not curable with present therapy
options, but the drugs that are available may help to slow its progression.
• Akatinol® (memantine) is an N-methyl-D-aspartate (NMDA) receptor antagonist in development
for the treatment of dementia caused by several neurologic conditions. An NDA for its use in
people with Alzheimer’s disease may be filed as early as the end of this year.
APPENDIX A
• A new delivery method is being developed for selegiline, a monoamine oxidase B (MAO-B)
inhibitor. Selegiline is available on the U.S. market as the generic and as the brand product,
Eldepryl®. The new form, Zelapar® (selegiline hydrochloride flashtab), delivers a low dose
that dissolves rapidly in the mouth — not only allowing it to begin working more quickly than
conventional oral dosage forms, but also potentially eliminating the difficulty that many
Parkinson’s patients have in swallowing tablets or capsules.
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
Long known to be a condition that affects children and adolescents, ADHD is now also recognized
as affecting adults, too. Although behavioral counseling and drug therapy each play important
parts in treating ADHD, treatment for both children and adults with ADHD centers on improving
core symptoms not necessarily on controlling behavior. Stimulants such as methylphenidate
are the mainstays of treatment. Antidepressants may also be useful as adjunctive treatment
for some patients.
• Three extended-release formulations of methylphenidate, the drug in Ritalin®, were launched
in 2000. Metadate®, Concerta® and Methylin® all offer once-daily dosing so children will not
have to take medication to school. Each is produced in various strengths, allowing doses to
be individualized.
65
APPENDIX B
64
• In the pipeline for MS is another beta interferon, Rebif® (recombinant interferon beta-1a).
Although a Biologics License Application (BLA) — the equivalent of an NDA for a biologically
derived product — has been filed for Rebif®, its approval may depend on the expiration of
orphan status for a currently available beta-interferon, Avonex® (interferon beta-1a), which
is scheduled for 2003.
APPENDIX A
APPENDIX B
Parkinson’s disease — sometimes called Parkinsonism — results from a deficiency of the
neurotransmitter dopamine. Characterized by tremor, rigidity and extreme slowness of
movement, its incidence rises in people older than 50 years of age.
• Last fall, a drug already approved for treating prostate cancer was given an additional indication
for the treatment of MS. Novantrone® (mitoxantrone for injection concentrate) can help reduce
relapses and neurologic dysfunction in people with specific types of progressive MS.
ACTIONS
ACTIONS
• Neotrofin® (leteprinim) is in Phase III trials for mild to moderate dementia of Alzheimer’s and in
earlier stages of trials for spinal cord injuries. Given orally, Neotrofin® stimulates the production
of multiple growth factors at the appropriate target sites in the CNS.
In multiple sclerosis (MS), nerve transmissions are interrupted when swelling and scar tissue
damages the myelin — tissue that surrounds nerve fibers in the CNS. Although MS has no cure,
beta interferons have proved useful for treating it.
DRUG
IMPORTANCE
DRUG
IMPORTANCE
At least a dozen other drugs are in development for Alzheimer’s. Among them:
• An NDA was submitted in October 2000 for the FDA to review another narcolepsy drug, Xyrem®
(sodium oxybate). If approved, it is likely to be designated as a controlled substance.
COST
FORECAST
• Another acetylcholinesterase inhibitor that also modulates nicotinic receptors is called Reminyl®
(galantamine). At this time, any clinical advantages that may be offered by the dual mechanism of action remain unknown. Reminyl® was approved in the first quarter of 2001 for the
symptomatic treatment of mild to moderate dementia of the Alzheimer’s type.
Once misunderstood and even dismissed as trivial, narcolepsy is now recognized as a serious
neurological condition typified by chronic, exaggerated sleepiness during daylight hours. Dreamlike hallucinations, sleep disruptions and transient weakness or paralysis are also common
narcolepsy symptoms. Until recently, drug treatments for narcolepsy were limited mainly to
antidepressants and stimulants like amphetamines. The 1999 approval of Provigil® (modafenil),
which seems to have a different mechanism of action than traditional stimulant-type drugs,
provides an alternative for many people with narcolepsy.
TRENDS IN
EXPENDITURES
• Exelon® (rivastigmine) was approved for Alzheimer’s in April 2000. Exelon® selectively
inhibits an enzyme called acetylcholinesterase in areas of the brain known to be damaged by
Alzheimer’s disease. Patients respond with more predictable physical behavior as well as with
better cognition. During clinical trials, however, a significant percentage of patients treated
with Exelon® experienced GI side effects such as anorexia, nausea and vomiting.
• A drug similar to selegiline, called rasagiline mesylate or TV-1012, has finished U.S. Phase III
trials in patients with early Parkinson’s disease that has not been treated previously. It will be
submitted to the FDA for once-a-day dosing. Late clinical trials continue for people with more
advanced Parkinson’s or those who have already been treated with levodopa.
INTRODUCTION
TRENDS IN
EXPENDITURES
2:39 PM
PREFACE
COST
FORECAST
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TABLE OF
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• In 2000, Zyprexa® (olanzapine), already approved for schizophrenia, won additional FDA approval
for the treatment of acute mania in bipolar disorder. It is also under FDA consideration for
agitation associated with psychotic illnesses.
• An NDA is expected to be submitted in 2001 or early 2002 for Zomaril® (iloperidone), an
antipsychotic agent in Phase III clinical trials for the treatment of schizophrenia.
• A new antipsychotic agent, aripiprazole, is currently in Phase III trials. With a different mechanism
of action than most currently available antipsychotic drugs, aripiprazole appears to be effective
for schizophrenia and also seems to cause relatively few side effects.
ANTIDEPRESSANTS
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
INTRODUCTION
TRENDS IN
EXPENDITURES
25
Zoloft ($84.42)
20
Paxil ($82.66)
15
Amitriptyline HCL ($12.89)
10
Celexa ($73.22)
Trazodone HCL ($25.17)
5
0
Effexor/XR ($95.94)
1996
1997
1998
1999
2000
• PMPY costs for antidepressants escalated another 17.4 percent in 2000, reaching $39.55.
A little less than half of this increase was due to rising utilization of drugs in this class.
Utilization of Prozac®, which peaked at 27.4 percent market share in 1994, continued its decline
to 17.4 percent in 2000. Market shares of Zoloft® and Paxil® remained stable at a combined
2000 market share of 31.5 percent, while the use of the newer agent, Celexa®, grew to 7.9 percent; the combined market share of Effexor® and Effexor® XR rose to 7.4 percent. The product
whose market share has grown the most — from 2.5 percent in 1997 to 7.5 percent in 2000 —
is Wellbutrin® SR (bupropion, extended release). The primary reason for the growth is its offlabel use as a smoking cessation tool, despite the availability of OTC products and of Zyban®
(bupropion, extended release), which is not covered by many health plans.
• In an unusual move, the FDA approved fluoxetine in the same strength and dosage form as
Prozac® under a new brand name, Sarafem®. Indicated for the treatment of premenstrual
dysphoric disorder, Sarafem® was re-named to avoid negative connotations that might be
associated with using an antidepressant.
67
APPENDIX B
66
Prozac ($116.54)
APPENDIX A
• Selective Serotonin Reuptake Inhibitors (SSRIs) — Prozac® (fluoxetine), Paxil® (paroxetine),
Zoloft® (sertraline), Luvox® (fluvoxamine) and Celexa® (citalopram)
• Serotonin Reuptake Inhibitors (SARIs) — Desyrel® (trazodone) and Serzone® (nefazodone)
• Selective Norepinephrine Reuptake Inhibitor (SNRI) — Effexor® (venlafaxine)
• Norepinephrine and Dopamine Reuptake Inhibitor — Wellbutrin® (bupropion)
• Noradrenergic and Specific Serotonin Antidepressant — Remeron® (mirtazapine)
%
30
ACTIONS
Although antidepressant drugs affect more than one neurotransmitter, the newer ones can be
grouped into five general classes based on their primary activity. For most patients, these newer
agents offer reduced side effects, low risk if overdosed, broader effectiveness and more selective
activity than TCAs or MAOIs. The classes are:
2000PMPY = $39.55
DRUG
IMPORTANCE
ACTIONS
% CHANGE IN PMPY COST
COST
FORECAST
APPENDIX A
ANTIDEPRESSANTS
17.4%
• In February 2001, an atypical antipsychotic called Geodon® (ziprasidone) — formerly named
Zeldox® — was approved by the FDA in both oral and injectable forms for schizophrenia. An
antagonist of both serotonin and dopamine, Geodon® is effective in treating anxiety and depression associated with schizophrenia. Its manufacturer has also applied for an indication in
treating agitation. The product labeling for Geodon® will carry a warning for cardiac side effects.
Clinical depression involves imbalances in chemical neurotransmitters — especially serotonin,
norepinephrine and dopamine. Some antidepressant drugs — tricyclics (TCAs) and monoamine
oxidase inhibitors (MAOIs) — have been in clinical use for nearly 50 years.
APPENDIX B
FIGURE A2 THERAPY CLASS DRUG MARKET SHARE TREND
TRENDS IN
EXPENDITURES
COST
FORECAST
Psychoses such as paranoia or schizophrenia are severe disorders that may involve distortions
of reality, fluctuations in personality and atypical social behaviors. Older antipsychotic drugs can
be associated with serious side effects, but newer drugs are more targeted — they may be more
effective with fewer side effects.
INTRODUCTION
DRUG
IMPORTANCE
• In Phase II trials for treatment of adult ADHD is a selective histamine H3 receptor antagonist,
Perceptin® (GT-2331). Further investigations are planned for its use in dementias and sleep disorders.
A guideline paper, “Pharmacological Treatment of Acute Major Depression,” was printed in the
May 2000 issue of Annals of Internal Medicine. In it, the American College of Physicians and the
American Society of Internal Medicine concluded that TCAs and SSRIs are equally effective. The
choice of drug treatment, they recommend, should be based on side effects, patient response and
physician/patient preference. Treatment should be evaluated after six weeks. Positive response
warrants continuation of drug therapy for four months or longer following acute remission. If
improvement in depressive symptoms is not evident after six weeks, the dose of drug can be
increased or a different drug can be tried.
PREFACE
PREFACE
• Phase III trials were completed in early 2001 for a methylphenidate patch, MethyPatch®
(methylphenidate transdermal delivery system). An NDA for its use in treating ADHD is not likely
to be filed with the FDA before next year, however, since further testing may be needed.
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• Another form of Prozac® received FDA approval for once weekly dosing relapse prevention during
the continuation phase of treatment for patients whose depression has stabilized with other
treatment. Prozac® WeeklyTM, contains 90mg of fluoxetine formulated with an enteric coating
that allows gradual drug release over seven days. It was approved in February 2001.
• Late in 2000, investigational trials for r-fluoxetine were abandoned after potentially serious
cardiac side effects were associated with its use.
ANTIANXIETY AGENTS
Anxiety disorders are characterized by chronically exaggerated feelings of fear or apprehension.
Hereditary, biological and environmental factors can all influence the development of anxiety
disorders. Obsessive-compulsive behaviors, panic attacks, generalized anxiety and phobias are
among the common types of anxiety disorders.
FIGURE A3 THERAPY CLASS DRUG MARKET SHARE TREND
TRENDS IN
EXPENDITURES
100
Generic ($31.55)
80
BuSpar ($115.90)
TRENDS IN
EXPENDITURES
Xanax ($72.65)
• Application has been submitted to the FDA for the approval of Luvox® for depression. It is
currently indicated for obsessive-compulsive disorder in adults and children. Tentative approval
for a generic, fluvoxamine, was given in November 2000, and the generic product has been
introduced to the market.
• Phase III trials have been completed for an SNRI, duloxetine.
• Also in development is a combination of fluoxetine and the antipsychotic drug, Zyprexa®
(olanzapine). If approved, the new combination will be used to treat patients who have
depression and psychosis or who have depression resistant to other therapy.
®
• Vestra (reboxetine) is still under FDA review for depression after new information was
submitted at the request of an FDA advisory panel.
Valium ($53.95)
40
Ativan ($62.47)
20
0
1996
1997
1998
1999
2000
• PMPY costs for this class grew 15.1 percent in 2000, although PMPY utilization increased by
only 5.9 percent.
• The generics market share remained fairly constant at 82.9 percent.
• In the summer of 2000, an antidepressant, Effexor® XR (venlafaxine, extended release) gained
FDA approval for generalized anxiety disorder.
DRUG
IMPORTANCE
• An NDA for escitalopram, an isomer of Celexa®, may be filed during the first half of 2001.
Results from Phase III trials of escitalopram show significant effectiveness for patients
with depression.
60
COST
FORECAST
COST
FORECAST
15.1%
2000 PMPY = $8.01
%
Future Trends
• The manufacturer of Paxil® has requested approval for a new indications in post-traumatic
stress disorder.
DRUG
IMPORTANCE
% CHANGE IN PMPY COST
• A rapid-dissolving form of Remeron® — Remeron® SolTabTM — has been approved. Launch is
expected in the first half of 2001.
INTRODUCTION
INTRODUCTION
ANTIANXIETY AGENTS
ACTIONS
Future Trends
• In March 2001, a federal court negated a new patent for BuSpar® (buspirone), opening the way
for generics to be introduced. The manufacturer of BuSpar® had listed the patent with the FDA
in a tactic to delay or prevent generic marketing. Phase III trials for a transdermal patch dosage
form of BuSpar® have been completed.
APPENDIX A
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
69
APPENDIX B
68
APPENDIX A
• Studies are being conducted on the use of the antidepressant Prozac® (fluoxetine) in treating
generalized anxiety disorder.
ACTIONS
APPENDIX B
PREFACE
PREFACE
TABLE OF
CONTENTS
TABLE OF
CONTENTS
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I N F L A M M AT I O N A N D PA I N M A N A G E M E N T
INTRODUCTION
TRENDS IN
EXPENDITURES
COST
FORECAST
• Currently completing Phase II trials, frakefamide (BCH-3963), represents a unique drug class
whose members act on pain receptors located outside the brain and spinal cord. Since frakefamide and similar drugs do not affect the CNS, they are not expected to produce side effects
such as sedation and respiratory depression that can occur with the use of narcotic analgesics.
ANTI-RHEUM (NSAIDS AND COX-2S)
Osteoarthritis (OA) and rheumatoid arthritis (RA), both characterized by joint damage, stiffness
and pain, are the two most common forms of arthritis. For most forms of arthritis, treatment
begins with pain management. Non-steroidal anti-inflammatory drugs (NSAIDs) are very effective
at relieving most types of mild to moderate pain, but they can cause stomach problems for some
people. The newer cyclo-oxygenase 2 inhibitors (COX-2s), Celebrex® (celecoxib) and Vioxx® (rofecoxib), offer similar pain relief with less chance of stomach complications from chronic use.
FIGURE A4 THERAPY CLASS DRUG MARKET SHARE TREND
ANTI-RHEUM (NSAIDS)
DRUG
IMPORTANCE
• The biological response modifier, Enbrel® (etanercept) has been granted a new indication
for the initial treatment of moderate rheumatoid arthritis. Because the demand has been
greater than expected, the manufacturers of Enbrel® have begun to enroll patients in a special
distribution program. Those patients who register will be considered first if temporary shortages
of Enbrel® occur.
• ABT-594, a synthetic adaptation of epibaditine toxin from the skin of poisonous South American
frogs, shows promise in early development for pain management. In a new class called cholinergic channel modulators, ABT-594 stops pain signals from reaching the brain. Investigators
report morphine-like efficacy without addiction.
COST
FORECAST
• In December 2000, the FDA approved a new indication for Botox® (botulinum toxin type A)
as well as a similar new drug, Myobloc® (botulinum toxin type B), for the treatment of cervical
dystonia. Also called spasmodic torticollis, cervical dystonia causes painful contraction of head,
neck and shoulder muscles. Injected botulinum toxin interrupts nerve signals to the affected
muscles, allowing them to loosen. Botox® has orphan drug status for the treatment of muscle
contracture in children with cerebral palsy.
• Prosaptide TX 14 (A), the first in another new class of pain relievers, has completed Phase II
trials. In animal studies, prosaptides protected nerves, relieved pain associated with nerve
stimulation and even promoted regeneration of damaged nerve fibers. Now entering Phase III
studies, prosaptide is being investigated for a number of pain syndromes, such as diabetic
neuropathy, accidental nerve injuries and nerve damage caused by chemotherapy.
TRENDS IN
EXPENDITURES
While proponents of the new standards contend that the abuse of controlled substances among
patients being treated for pain will not increase, national law enforcement officials are concerned
that the theft of prescription pain drugs for recreational use is on the rise. In accounts that
were highly publicized in early 2001, the popular press reported a surge in thefts involving
narcotic analgesics. Manufacturers of the drugs are working with government officials to
address the problem.
• In June 2000, the FDA issued an Approvable letter for ziconotide, the first neuron-specific N-type
calcium channel inhibitor. Derived from the venom of the marine cone snail, ziconotide will be used
only in hospitals for treatment of severe chronic pain and for pain associated with head trauma.
INTRODUCTION
In January 2001, new standards for the treatment of pain were implemented. Developed by
the Joint Commission on the Accreditation of Healthcare Organizations, the standards require
an initial assessment of pain levels followed by regular monitoring of and treatment for pain
experienced by patients in hospitals or other healthcare institutions. Patient-reported pain levels
are recorded in charts as a vital sign just like blood pressure and temperature readings. Designed
to address the problem of inadequate pain control, the standards will likely lead to increased use
of opiods in outpatient settings, as well.
Future Trends
PREFACE
PREFACE
Pain can be a symptom of almost every major health condition. It can be acute or chronic, mild
or disabling, localized or general. Everyone experiences pain differently — what is tolerable for
one person may be excruciating for someone else.
DRUG
IMPORTANCE
TABLE OF
CONTENTS
TABLE OF
CONTENTS
22501_appA
% CHANGE IN PMPY COST
2000PMPY = $24.72
%
25
Celebrex ($93.75)
Vioxx ($83.03)
Ibuprofen ($14.67)
15
Naproxen/Sodium ($50.19)
10
Relafen ($77.97)
5
70
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
Daypro ($87.37)
1996
1997
1998
1999
2000
71
APPENDIX B
APPENDIX B
0
APPENDIX A
APPENDIX A
20
• In January 2001, a third hyaluronic acid derivative, Supartz® (sodium hyaluronate) was
approved for the treatment of osteoarthritis of the knee. Like its predecessors, Synvisc® (hylan
GF 20) and Hyalgan® (sodium hyaluronate), Supartz® is a viscous cushioning substance that
must be injected directly into affected knee joints.
ACTIONS
ACTIONS
37.9%
• A drug that has long been used to treat rheumatoid arthritis in adults is now indicated for
children, too. Azulfidine® EN-Tabs (sulfasalazine delayed release) were FDA approved in 2000
for the treatment in children age 6 and older of juvenile rheumatoid arthritis that has not
responded to therapy with NSAIDs.
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TABLE OF
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22501_appA
• A generic for Lodine® (etodolac) was marketed in 2000; a generic for Daypro® (oxaprozin) was
approved but not launched as of March 2001; and patent protection for Relafen® (nabumetone)
has expired although its generic has not been approved.
INTRODUCTION
DRUG
IMPORTANCE
ACTIONS
Future Trends
FIGURE A5 THERAPY CLASS DRUG MARKET SHARE TREND
• The FDA has requested additional studies to support a biological license application (BLA) that
was filed in late 1999 for Kineret® (anakinra). A BLA is the equivalent of an NDA for products
derived from biological material such as a protein or nucleic acid. Kineret is an interleukin-1
receptor agonist (IL-1ra) that has demonstrated the potential to reduce bone and cartilage
destruction as well as to decrease inflammation in patients with RA. If approved, Kineret® will
compete with Enbrel® and Remicade® in the rapidly growing RA market.
NARCOTIC ANALGESICS
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
%
80
Generic ($15.52)
70
Ultram ($54.09)
60
Darvocet-N 100 ($37.07)
50
40
30
20
10
0
1996
1997
1998
1999
2000
73
APPENDIX B
72
34.8%
2000PMPY = $12.46
APPENDIX A
• Additional COX-2s are in various stages of development. The closest to market is probably
parecoxib for which an NDA was submitted in October 2000. Its manufacturer anticipates that
approximately one year will be needed for FDA review. An injectable product, parecoxib is intended for the management of mild to moderate postsurgical pain and, in combination with opiods
like morphine, for the management of more severe postsurgical pain. Valdecoxib, a prodrug
of parecoxib, is an oral agent in Phase III testing for pain from several conditions — including
dysmenorrhea, dental pain, OA and RA. An NDA for valdecoxib is expected to be filed in 2001.
Also in Phase III clinical trials, another COX-2, etoricoxib (MK-663), has been effective in treating acute dental pain and in managing chronic pain of both OA and RA. An NDA for it, too, may
be filed by the end of 2001.
% CHANGE IN PMPY COST
ACTIONS
APPENDIX A
Among the most effective painkillers known, narcotics also produce potentially serious side
effects such as respiratory depression. If they are used improperly, they can be both physically
and psychologically addicting. Once reserved for intractable pain, narcotics are beginning to
be used more widely. New guidelines for pain management will probably lead to increased use
of narcotics in ambulatory populations. According to a consensus statement from the American
Academy of Pain Medicine and the American Pain Society, however, the addiction is not likely
to result in people who use narcotics for pain relief.
DRUG
IMPORTANCE
APPENDIX B
• Early in 2001, Remicade® (infliximab) was granted a new indication in combination with methotrexate,
for slowing the development of joint damage in patients with moderate to severe RA that has not
shown improvement when treated with methotrexate alone. Originally approved for the second-line
treatment of Crohn’s disease — an inflammatory bowel disease — Remicade® is a monoclonal
antibody with activity against the inflammation associated with some autoimmune conditions.
NARCOTIC ANALGESICS
COST
FORECAST
COST
FORECAST
• Mobic® (meloxicam) was approved in 2000. Indicated for relief of the signs and symptoms of
OA, Mobic® will compete with generic NSAIDs as well as with COX-2s.
• In an effort to avoid the stomach irritation caused by oral dosage forms, manufacturers are
beginning to develop topical forms of NSAIDs and other pain relievers. An NDA is pending for
Pennsaid® (diclofenac gel) while the manufacturer provides more information to the FDA.
Pennsaid® has been approved in Europe. Benefen® is the brand name for an ibuprofen gel
being investigated for OA. Latranal®, an undisclosed combination of topical pain relievers,
begins Phase II trials in the U.S. this year. In addition, a topical form of clonidine is undergoing
new trials for supplemental information requested by the FDA. To be indicated initially for the
treatment of neuropathic pain, clonidine gel also may be investigated for arthritic pain.
TRENDS IN
EXPENDITURES
TRENDS IN
EXPENDITURES
• Since 1998, the combined market share for Relafen® (nabumetone), Lodine® (etodolac), Lodine®
XL (etodolac extended-release) and Daypro® (oxaprozin), all branded products, was cut in half
to under 10 percent in 2000.
• An NDA filing for pregabalin in the treatment of neuropathic pain will be delayed after Phase III
trials were put on clinical hold early in 2001. The FDA requested further investigation of pregabalin-treated test animals that appear to have developed more tumors than control animals.
INTRODUCTION
• This dramatic cost increase was driven primarily by the use of newly introduced more expensive
COX-2 products Celebrex® and Vioxx®. The average cost for both products rose about 10 percent
— to $93.75 for Celebrex® and $83.03 for Vioxx®, compared to the AWP cost of $14.67 for
ibuprofen and $55.32 for naproxen. Since being introduced in 1999, the combined market
for Celebrex® and Vioxx® has grown to 39.6 percent.
• Early in development is another new class of anti-inflammatory drugs called COX/LO inhibitors. By
blocking both COX-2 and another enzyme, 5-lipoxygenase, drugs in this class inhibit the production
of both prostaglandins — which stimulate pain and inflammation and leukotrienes — which cause
stomach damage. ML 300 is a COX/LO inhibitor undergoing Phase III clinical trials early in 2001.
PREFACE
PREFACE
• PMPY costs for anti-inflammatories grew by 37.9 percent to $24.72; this rate of growth was the
highest experienced by any of the top 25 therapy classes. Only about one-third of this rate of
increase is attributable to rising utilization.
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TABLE OF
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TABLE OF
CONTENTS
22501_appA
INTRODUCTION
Migraines are among the most debilitating types of headache. Resulting from contraction, then
expansion and inflammation of blood vessels in the brain, migraines usually follow a distinctive
pattern. Most commonly affecting one side of the head, migraines are frequently associated with
nausea, vomiting and exaggerated sensitivity to light, sound and smells. Some are announced by
a prodome or aura — a preliminary set of symptoms that can include visual disturbances and
numbness or tingling in the hands and feet. The tendency to have migraines can run in families,
and women are more likely than men to get them.
INTRODUCTION
• PMPY utilization for this class grew by 9.9 percent. In contrast the average prescription
cost rose by about 23 percent. Per prescription cost increases of 21 percent were seen for
generics, which accounted for a substantial but declining 71.3 percent of the total class
market share. In 2000 Ultram® (tramadol) held its leading position among branded products
with a 7.3 percent share of the market.
MIGRAINE PRODUCTS
FIGURE A6 THERAPY CLASS DRUG MARKET SHARE TREND
• The market share for OxyContin® (oxycodone controlled release) only grew from 2 percent to
3.3 percent. At an average AWP cost per prescription of $207.42, even this slight rise
in use contributed to the overall increase in the class cost per prescription to $30.09.
MIGRAINE PRODUCTS
PREFACE
PREFACE
• The increasing cost escalation in the narcotic analgesic class continued in 2000. After growing
20.6 percent between 1997 and 1998, and another 31.1 percent in 1999, the PMPY cost for
narcotic analgesics grew yet another 34.8 percent in 2000 to $12.46.
% CHANGE IN PMPY COST
10.9%
2000PMPY = $7.09
• MorphiDex® (morphine and dextromethorphan) is in additional testing after an original 1998
NDA was denied by the FDA. A resubmission may be as early as next year.
80
Imitrex ($190.67)
70
Generic ($17.16)
60
50
Zomig ($156.14)
40
Amerge ($185.92)
30
Maxalt/MLT ($136.56)
20
• New delivery forms for narcotics are also being investigated. For example, an NDA is under FDA
review for Morphelan® ROERTM (morphine rapid-onset, extended-release) that would be dosed on
a once daily schedule. Another study involves the AERx® system, an investigational device to
deliver morphine through inhalation. It is in Phase II trials.
COST
FORECAST
Midrin ($18.37)
10
0
1996
1997
1998
1999
2000
ACTIONS
ACTIONS
• The market share for Imitrex® (sumatriptan injection, nasal spray and tablets) continued
to decline to 47.1 percent. Lost market share has gone to Zomig® (zolmitriptan), Amerge®
(naratriptan) and Maxalt®/ Maxalt MLT® (rizatriptan), which saw their combined market
share rise 26.9 percent in 2000.
DRUG
IMPORTANCE
• The PMPY cost of migraine products rose by 10.9 percent from $6.40 in 1999 to $7.09 in 2000.
DRUG
IMPORTANCE
COST
FORECAST
• An oral opiod that may not have as much associated addiction potential as current narcotics is
in Phase III of clinical testing. An application for the approval of Dirame® (propiram) may be
filed this year for FDA consideration in the treatment of moderate to severe pain.
TRENDS IN
EXPENDITURES
TRENDS IN
EXPENDITURES
%
Future Trends
• A melt-in-the-mouth formulation of Zomig — Zomig-ZMT® (zolmitriptan orally disintegrating
tablets) was approved by the FDA in February 2001.
Future Trends
APPENDIX A
• Two other new triptans, Relpax® (eletriptan) and Axert® (almotriptan), were both found
Approvable in December 2000. Depending on when final approval is given, one or both
may be launched in the second half of 2001.
74
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
75
APPENDIX B
APPENDIX B
APPENDIX A
• Last May, Miguard® (frovatriptan) received Approvable status for treatment of migraines.
Final FDA approval is pending the review of additional information that was provided by the
manufacturer late in 2000.
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TABLE OF
CONTENTS
TABLE OF
CONTENTS
22501_appA
FIGURE A7 THERAPY CLASS DRUG MARKET SHARE TREND
ANTICONVULSANTS
% CHANGE IN PMPY COST
INTRODUCTION
• Neurontin® (gabapentin) continued to gain market share, attaining a 21.5 percent level in 2000
— up from 17.1 percent in 1999. Market share for generic products also grew to 30.2 percent.
However, some generics may not be absorbed in the same ways as their branded counterparts.
• The market share for Depakote®, Dilantin®, Tegretol®, Tegretol® XR (carbamazepine extended
release) and Klonopin® (clonazepam) continued to decline from 54 percent in 1998 to
36.6 percent in 2000.
• In a move to preserve brand-only status for Neurontin®, its manufacturer obtained a new patent
from the FDA. The generic company that has approval for gabapentin countered with a lawsuit,
but no decision has been reached.
• Production of Mesantoin® (mephenytoin), which had been used for patients whose seizures were
not controlled by other drugs, was discontinued during 2000. The manufacturer stopped making
it because it had lost market share to newer drugs that have fewer side effects.
TRENDS IN
EXPENDITURES
Since 1993, several new anticonvulsant drugs — also called anti-epilepsy drugs (AEDs) —
have been introduced in the United States. All of the new drugs are approved for use in combination with other AEDs, but only a few are indicated for monotherapy. Generally, treatment for
people who are newly diagnosed with a seizure disorder begins with older traditional AEDs like
Tegretol®/Tegretol® XR (carbamazepine), Dilantin® (phenytoin) and Depakene® or Depakote®
(valproic acid derivatives). With established efficacy and lower cost, these older drugs offer
general safety in both children and adults. Many of the newer agents, however, offer safer sideeffect profiles and lower potential to interact with other drugs. Frequently, treatment requires
the use of more than one drug at a time.
• After growing in cost by 29 percent in 1999, anticonvulsant PMPY costs increased by another
29.9 percent to $9.26 in 2000 due to increases in both use and cost per prescription.
INTRODUCTION
TRENDS IN
EXPENDITURES
Epilepsy is a broad term for the susceptibility to have recurring seizures. The result of dysfunctions in the brain’s electrical conduction, seizures often have no clear cause. They can begin or
end at any age and they may take many different forms — including convulsions, muscle spasms
and altered consciousness.
PREFACE
PREFACE
ANTICONVULSANTS
29.9%
35
Generic ($39.78)
30
Neurontin ($118.24)
25
Depakote/Sprinkle ($95.20)
20
Dilantin ($28.50)
15
Tegretol/XR ($49.35)
• Phase II clinical trials continue for ganaxolone (CCD 1042) for the treatment of migraine
headache as well as of various forms of epilepsy. Ganaxolone already has orphan status for
treating infantile spasms — a type of epilepsy that first appears between three months and
six months of age.
DRUG
IMPORTANCE
DRUG
IMPORTANCE
Future Trends
• An NDA for pregabalin, derived from Neurontin® and made by the same manufacturer, could be
filed this year for the first of several indications including epilepsy.
%
10
1996
1997
1998
1999
2000
76
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
77
APPENDIX B
APPENDIX B
APPENDIX A
APPENDIX A
ACTIONS
ACTIONS
5
COST
FORECAST
COST
FORECAST
2000 PMPY = $9.26
PREFACE
2:39 PM
Page 78
C A R D I O VA S C U L A R
COST
FORECAST
DRUG
IMPORTANCE
• After additional investigations were done, an NDA was refiled in January 2001 for Natrecor®
(nesiritide). It is a recombinant version of b-type natriuretic peptide (BNP), a hormone the body
uses to compensate for excess fluid. Intended to relieve symptoms of congestive heart failure,
Natrecor® relaxes blood vessels as well as promoting excretion of excess fluid.
Coronary Artery Disease (CAD): When cholesterol and other substances build up inside the
blood vessels that supply the heart, the resulting clogged, stiffened and damaged arteries can
no longer provide adequate oxygen. Heart function decreases.
• Another new class of heart drugs is represented by Tracleer® (bosentan). Belonging to a group
called dual endothelin receptor antagonists (ERAs), Tracleer® and drugs like it block endothelin,
a naturally occurring vasoconstrictor. An NDA has been submitted for the use of Tracleer® in
treating pulmonary hypertension — abnormally high blood pressure in the arteries that carry
blood between the heart and the lungs — while Phase III trials continue for its effectiveness
in congestive heart failure. It will be taken orally. A second ERA, tezosentan, is in Phase III
of development. Tezosentan is an intravenous drug being studied for the treatment of acute
heart failure.
Hypertension: Usually asymptomatic, hypertension or high blood pressure often has no
apparent cause. Hypertension increases the workload on the heart, which can result in heart
attack or stroke.
• Eplerenone is being investigated for use in hypertension, congestive heart failure and MI.
Similar to an older drug called spironolactone, eplerenone blocks aldosterone receptors to
increase water excretion. It is in Phase III trials in several countries.
Myocardial Infarction (MI): A sudden MI, or heart attack, occurs if the blood supply to the heart
is blocked, and oxygen cannot reach part of the heart. The part of the heart tissue deprived of
oxygen dies.
• The first partial fatty acid oxidation inhibitor (pFOX), ranolazine is in Phase III trials for the
treatment of chronic stable angina and congestive heart failure. Drugs of its type reduce the
metabolism of fatty acids — forcing the body to metabolize glucose instead. As one result, the
heart pumps more efficiently. Blood pressure and heart rate are affected minimally, if at all.
Congestive Heart Failure (CHF): A heart weakened by coronary artery disease, hypertension
or numerous other conditions gradually loses the ability to beat hard enough to circulate blood
effectively throughout the body.
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
Drugs used mainly — but not exclusively — to treat hypertension fall into several sub-classes.
Angiotensin converting enzyme inhibitors (ACEIs) block production of an enzyme that raises blood
pressure. They are used in congestive heart failure, hypertension and MI. In recent studies, they
have demonstrated protective effects on heart and kidney function. A newer class than the ACEIs,
angiotensin receptor blockers (ARBs) inhibit the same enzyme that ACEIs do but in a different way.
79
APPENDIX B
78
ANTIHYPERTENSIVES
APPENDIX A
Numerous drug classes work on the heart or blood vessels to treat the diseases that affect the
cardiovascular system. Some of the drugs are intended only for specific conditions, but many
drugs can be used to treat more than one type of heart disease. The beta-blockers, for example,
are used in treating hypertension, angina, MI, CHF, some arrhythmias and even non-cardiac
conditions such as migraine headaches. As scientists gain new understanding of cardiovascular
functioning, new classes of cardiac drugs are being developed.
ACTIONS
ACTIONS
• Additional trials are under way for Vanlev® (omapatrilat), the first drug in a new class called
vasopeptidase inhibitors (VPIs). VPIs block two enzymes to help lower blood pressure and also
help relieve heart failure. In original investigations, Vanlev® was effective for lowering blood
pressure, but its use was associated with a serious side effect, angioedema, in a few patients.
The FDA requested further study. Although the original NDA was withdrawn, it is expected to be
resubmitted for approval later this year.
DRUG
IMPORTANCE
APPENDIX A
Arrhythmias: When the electrical system that controls the heart is interrupted, the heart can
beat too rapidly, too slowly or unpredictably. Blood flow is erratic, and life-threatening results
can occur.
Future Trends
COST
FORECAST
APPENDIX B
Angina: Squeezing pressure or chest pain that results from an inadequate supply of oxygen to the
heart muscle.
• An NDA is under FDA review for a new combination product, BiDil® (hydralazine and isosorbide)
that has shown significant effectiveness for African-Americans who suffer from heart failure.
TRENDS IN
EXPENDITURES
TRENDS IN
EXPENDITURES
Among the most common cardiovascular conditions are:
• Generics are now available for three alpha-blockers, Hytrin® (terazosin), Cardura® (doxazosin)
and Minipres® (prazosin). Currently, alpha-blockers are used more for treating benign prostatic
hyperplasia (BHP) than for cardiovascular conditions.
INTRODUCTION
Many different but often interrelated conditions fall into the category of heart disease. Involving
the blood vessels as well as the heart itself, heart problems are more accurately described as
cardiovascular conditions. Frequently, they are associated with other serious diseases such as
diabetes. Some ethnic groups are more prone to cardiovascular problems, and young or middleaged men suffer more cardiovascular disease than women in the same age groups do. Still
cardiovascular diseases are the number one cause of death for both sexes and in all ethnic
groups. Typically chronic with few or no early symptoms, the effects of cardiovascular diseases
sometimes are seen abruptly — in a heart attack or a stroke. Primarily regarded as diseases
of aging, cardiovascular conditions are being diagnosed at younger ages. Some experts are
concerned that a rise in obesity among U.S. children and adolescents will lead to earlier
cardiovascular problems.
PREFACE
INTRODUCTION
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CALCIUM BLOCKERS
FIGURE A8 THERAPY CLASS DRUG MARKET SHARE TREND
% CHANGE IN PMPY COST
16.6%
2000 PMPY = $23.74
%
Zestril ($36.38)
15
FIGURE A9 THERAPY CLASS DRUG MARKET SHARE TREND
Lotensin ($31.57)
CALCIUM BLOCKERS
Prinivil ($36.82)
2.5%
1996
1997
1998
1999
2000 PMPY = $14.11
%
Cozaar ($53.67)
35
Hyzaar ($53.23)
30
2000
Norvasc ($57.68)
TRENDS IN
EXPENDITURES
0
% CHANGE IN PMPY COST
Vasotec ($55.53)
10
5
TRENDS IN
EXPENDITURES
Accupril ($38.03)
INTRODUCTION
INTRODUCTION
20
As the most abundant mineral in the body, calcium is obviously a major component of teeth and
bones. It is also involved in body functions such as muscle contraction. Calcium blockers selectively affect muscles in artery walls — causing them to relax. Consequently, resistance to the
flow of blood goes down and so does blood pressure. Calcium blockers are also used to relieve
angina and to treat some types of arrhythmia.
Generic ($50.94)
25
Procardia XL ($73.59)
20
Adalat CC ($66.65)
15
• 2000 PMPY costs for antihypertensives grew at about the same pace as overall PMPY costs.
Most of the 16.6 percent cost growth in this class came from the 9.6 percent rise in utilization.
PREFACE
PREFACE
ANTIHYPERTENSIVES
Cardizem CD ($69.74)
10
• Clinical studies continue to support potential new indications for ACEIs. In February 2000, for
instance, Zestril® (lisinopril) was approved in high doses (up to 35mg once a day) for the treatment of heart failure. The following October, Altace® (ramipril) received approval for reducing
the risk of heart attacks in patients with known heart disease, stroke or diabetes. Altace® may
be used in diabetic patients with normal blood pressure.
0
1996
1997
1998
1999
2000
• As has been the trend since 1994, 2000 PMPY cost for calcium blockers was relatively flat.
Between 1999 and 2000, utilization of these products dropped by 1.9 percent.
DRUG
IMPORTANCE
DRUG
IMPORTANCE
• The market share among the myriad of products in this class changed little between 1999
and 2000.
COST
FORECAST
COST
FORECAST
5
• The market share for generic calcium blockers continued to increase reaching 34.1 percent
in 2000.
• Rated as equivalent to Vasotec®, the generic enalapril, reached the U.S. market in late 2000.
• Lisinopril, the generic for Zestril and Prinivil , was granted tentative approval in January 2001.
It will not be marketed, though, until the expiration of the Prinivil®/Zestril® patent scheduled for
the end of 2001.
• Based on positive findings from the Valsartan Heart Failure Trial (val-HeFT), the manufacturer
of Diovan® (valsartan) has requested FDA approval for a new indication in treating heart failure.
When Diovan® was added to standard drug therapy, death and disability among members of the
group receiving valsartan declined significantly. Whether other ARBs will provide similar benefits has not yet been studied.
• Norvasc® (amlodipine) continued to dominate the branded market share in this class growing
to 32.8 percent in 2000.
• Correspondingly, the market shares for Cardizem® CD (diltiazem extended-release capsules)
and Procardia® XL (nifedipine extended release), continued to erode to 4.5 percent and
7.8 percent, respectively.
• A generic equivalent to Procardia® XL was approved during 2000. A previously marketed generic
was equivalent to Adalat® CC (nifedipine extended release). Because of formulation differences,
the two generics are not interchangeable and only the one designated by the FDA as A rated to
the corresponding brand name may be substituted for that brand.
APPENDIX A
APPENDIX A
®
ACTIONS
ACTIONS
®
• Application for approval of a new ARB, olmesartan, was filed with the FDA in July 2000.
If approved, it will be indicated for hypertension.
80
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
Future Trends
• Patent protection for Plendil® (felodipine) is scheduled to expire in June 2001.
81
APPENDIX B
APPENDIX B
Future Trends
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BETA BLOCKERS
% CHANGE IN PMPY COST
15.7%
2000 PMPY = $8.91
Generic ($30.00)
70
Toprol XL ($26.82)
60
50
Tenormin ($45.85)
40
Lopressor ($40.16)
30
Corgard ($67.79)
0
1996
1997
1998
1999
2000
• The overall 2000 PMPY cost for beta blockers increased 15.7 percent over 1999 levels to $8.91.
This growth was about equally attributable to utilization and per prescription cost increases.
• Despite losing some ground compared to 1999, generics continued to dominate this class with
a 72.2 percent market share in 2000.
Consuming too much dietary fat can be a major contributor to cardiovascular disease. Ordinarily,
the body breaks down fat from food and then fuses it to proteins. The resulting lipoproteins are
carried away in the bloodstream and stored for later use. When too much fat of the so-called bad
types — mainly triglycerides and low-density lipoproteins (LDLs) — builds up in the blood, it
gradually accumulates on artery walls. As a result, arteries become stiff, constricted or even
blocked and cardiovascular diseases result. High-density lipoproteins (HDLs) are considered good
because they take cholesterol to the liver where it is made into bile. Raised levels of HDL generally
translate into a lowered risk of coronary artery disease.
The best ways to improve overall cholesterol levels are to limit dietary fat consumption, maintain
a reasonable weight and exercise regularly. Such lifestyle changes are hard to implement and
even harder to continue, so drug therapy is often a part of cholesterol reduction.
The four main classes of drugs used to reduce cholesterol in the blood are:
Bile-Acid Binding Agents: Questran® (cholestyramine), Colestid® (colestipol) and
Welchol® (colesevelam)
• Approved in the summer of 2000, Betapace® AF (sotalol for atrial fibrillation) is a different oral
dosage form that is not interchangeable with either Betapace® or the generic. Because it may
cause potentially serious side effects, Betapace® AF must be given under medical supervision.
Fibric Acid Derivatives: Lopid® (gemfibrozil), Atromid-S® (clofibrate) and Tricor® (fenofibrate)
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
Niacin: NiaSpan® (niacin controlled release) and others
83
APPENDIX B
82
APPENDIX A
• The already large group of generic beta blockers grew in 2000 with the approvals of sotalol
(generic Betapace®) and bisoprolol (generic Zebeta®).
ACTIONS
• Among the branded products, Toprol XL (metoprolol extended-release), is the largest seller,
growing steadily from a 3.1 percent market share in 1994 to 17.1 percent in 2000.
HMG-CoA Reductase Inhibitors (HMG CoAs), also called statins: Baycol® (cerivastatin),
Lescol® (fluvastatin), Lipitor® (atorvastatin), Mevacor® (lovastatin), Pravachol® (pravastatin)
and Zocor® (simvastatin)
®
ACTIONS
ANTIHYPERLIPIDEMICS
DRUG
IMPORTANCE
DRUG
IMPORTANCE
10
• Development of esprolol, a beta blocker that would be delivered in quick-acting sublingual form,
is on hold while the manufacturer seeks a partner to market the drug. In Phase II trials, esprolol
was studied for treatment of angina, anxiety and migraine.
COST
FORECAST
COST
FORECAST
20
Future Trends
TRENDS IN
EXPENDITURES
TRENDS IN
EXPENDITURES
80
APPENDIX A
• Results from the Carvedilol Prospective Randomized Clinical Survival Trial (COPERNICUS)
showed that treatment with Coreg® (carvedilol) reduced the risk of death or hospitalization
due to heart failure by nearly a third in patients with advanced stages of the disease who
were already taking an ACEI. Coreg® is not due to go generic for several years.
FIGURE A10 THERAPY CLASS DRUG MARKET SHARE TREND
%
APPENDIX B
• Based on the results of the Metoprolol CR/XL (Controlled Release) Randomized Intervention
Trial in Heart Failure (MERIT-HF), Toprol®-XL has received additional FDA approval for therapy
of stable heart failure from ischemic, hypertensive or cardiomyopathic origin.
INTRODUCTION
INTRODUCTION
Beta blockers are useful for angina and certain arrhythmias as well as for hypertension. Once
thought to worsen heart failure, beta blockers are being used more among heart failure patients
in recent years after ongoing studies showed their effectiveness in combination with other drugs.
Beta blockers are less effective in some groups of patients and other patients are not able to
tolerate their side effects. Some beta blockers are used fairly often for migraine prevention and
situational anxiety.
PREFACE
PREFACE
BETA BLOCKERS
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Future Trends
FIGURE A11 THERAPY CLASS DRUG MARKET SHARE TREND
% CHANGE IN PMPY COST
23.4%
2000 PMPY = $32.28
%
60
Lipitor ($83.41)
Zocor ($116.86)
40
Pravachol ($99.08)
30
Gemfibrozil ($66.20)
20
Lescol ($46.44)
Mevacor ($113.07)
Lopid ($85.08)
1996
1997
1998
1999
2000
• Phase II trials for a new type of antihyperlipidemic are under way in the United States.
CardioRex®, a unique plant-based sterol compound is being investigated for treatment of
primary hypercholesterolemia.
TRENDS IN
EXPENDITURES
TRENDS IN
EXPENDITURES
10
• At least two new statins are being studied. Crestor® (rosuvastatin) purported to be a super
statin — more effective than others already on the market — is in Phase III trials. An NDA may
be filed for its approval by the end of this year. Itavastatin is earlier in U.S. development but
it is expected to be approved in Japan this year.
INTRODUCTION
INTRODUCTION
50
0
• An NDA was filed in September 2000 for the first of several combination products in development for lowering cholesterol. Formerly called Nicostatin®, this drug combines lovastatin with
extended-release niacin. A second still unnamed product will soon begin Phase III trials. This
product combines simvastatin with ezetimibe, an investigational agent that blocks the body’s
absorption of cholesterol from food.
PREFACE
PREFACE
ANTIHYPERLIPIDEMICS
• Patent protection for Mevacor® is slated to expire in the summer of 2001.
• Lipitor® continued its meteoric success since its March 1997 market entry. In 1997, Lipitor®
claimed a 14.1 percent market share, a level that rose to 51.8 percent in 2000. In contrast,
the market share for Pravachol® dropped from 16.4 percent in 1999 to 15.7 percent to in 2000.
The market share for Zocor®/Mevacor® dropped to 17.2 percent and for Lescol® to 2.9 percent.
• In June 2000, the FDA approved Welchol® the first new bile-acid binding product in a number of
years. To be used in combination with diet or with a statin, Welchol® comes as tablets and capsules, so it is much easier to take than earlier bile-acid binders that had to be mixed in water.
DRUG
IMPORTANCE
DRUG
IMPORTANCE
COST
FORECAST
COST
FORECAST
• Fueled by a large growth in utilization, overall PMPY expenditures for antihyperlipidemics rose
by 23.4 percent to $32.28.
APPENDIX A
• A higher-dose extended release form of Lescol® — Lescol® XL was approved in October 2000.
The higher dose is indicated for initial therapy in addition to dietary restrictions.
• The FDA once again rejected the immediate possibility of OTC statins. In denying the request
from manufacturers who want to produce lower strength non-prescription statins, members of
an FDA advisory panel concluded that treating high cholesterol requires professional monitoring
to be sure it is successful.
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
85
APPENDIX B
84
APPENDIX A
APPENDIX B
ACTIONS
ACTIONS
• In July 2000, Baycol® received approval for both a new higher strength — 0.8mg — and a new
indication — for raising HDL.
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R E S P I R AT O R Y
Respiratory conditions affect breathing. They can be acute like occasional colds, recurring like
seasonal allergies or chronic like asthma. Some respiratory conditions are relatively minor; others
are literally life-threatening. Many of the medications used to treat them are targeted directly to
affected tissues. Some are inhaled through the mouth, for example, to reach the lungs quicker.
Nasal sprays and eye drops deliver specially formulated drugs directly to affected areas so relief
is faster and systemic side effects are limited.
Results of a study released in November 2000 show that inhaled corticosteroids (ICSs) provide
safe and effective asthma treatment for children. Previously, concerns that corticosteroids
inhibited skeletal growth limited their use in children.
PREFACE
PREFACE
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FIGURE A12 THERAPY CLASS DRUG MARKET SHARE TREND
ANTIASTHMATICS
% CHANGE IN PMPY COST
%
30
Receiving new attention in drug development is chronic obstructive pulmonary disease (COPD).
Unlike asthma, which generally affects a young population — in 1996 10.5 million of the 14.5
million Americans with asthma were under the age of 45 — COPD is primarily a condition of older
people. Smokers and people who have worked in dusty, polluted environments are especially likely
to have COPD. Until recently, treatment for COPD was limited to many of the same drugs used to
treat asthma. Among several new types of drugs in development for COPD are:
Serevent/Diskus ($72.09)
15
Azmacort ($60.31)
10
Vanceril ($48.67)
5
COST
FORECAST
1998
1999
2000
Spiriva® (tiotropium): Currently in Phase III clinical trials for COPD, Spiriva® is a long-acting
anticholinergic drug that dilates bronchial passages. Submission of an NDA for FDA approval is
planned for late 2001.
Viozan® (AR-C68397AA): An agonist of both dopamine and beta-2 receptors, Viozan® may also
be filed for FDA approval in the treatment of COPD within the next year. It is administered as a
powder through an inhalation device.
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
• The market share for the long-acting beta agonist Serevent® (salmeterol) remained stable
at 7.5 percent. Because Serevent® has a slow (15 minute-30 minute) onset of action, it should
not be used to treat acute asthma symptoms. It is used instead as a daily controller medication, often in combination with an anti-inflammatory agent.
87
APPENDIX B
86
• The newest controller medications for asthma are the leukotriene modifiers — Accolate®
(zafirlukast), Zyflo® (zileuton) and Singulair® (montelukast). The National Asthma Education
and Prevention Program (NAEPP) guidelines list these products as an alternative to ICSs in mild
persistent asthma. Taken as tablets, all the leukotriene modifiers are for long-term control of
asthma so they must be taken continually. These products have low overall market share because
they are usually either prescribed in combination with other products or used as a secondline therapy. The market share for Singulair® continued to grow from 2.2 percent in 1998 to
10.5 percent in 2000, while the market for Accolate® rose slightly to 3.3 percent.
APPENDIX A
Asthma is a chronic inflammatory respiratory disease that is classified by four stages of severity.
Specific treatment depends on the stage of the condition. In general, however, two types of drugs
are used to treat asthma. To decrease inflammation and help prevent attacks, long-lasting controllers are taken on a regular basis. Corticosteroids and leukotriene inhibitors are two classes
of asthma controllers. The second type of asthma drugs provides short-acting relief when attacks
have started. Short-acting beta agonists and anticholinergic agents are asthma relievers —
often called rescue drugs.
• Albuterol (brand name Proventil® or Ventolin®) is the most widely used inhaled beta agonist.
Albuterol inhalers have been available generically since early 1996. The market share for the
generic forms dropped slightly from 26 percent in 1999 to 24.7 percent in 2000.
ACTIONS
In 2000, the FDA approved a new anti-allergy eye drop — Optivar® (azelastine) — that contains
the same drug in the nasal spray, Astelin®. Optivar® is similar to three other anti-allergy eye drops
that were introduced in 1999.
• In 2000 PMPY cost of antiasthmatics grew by 12.7 percent to $15.40, despite less than a one
percent rise in PMPY utilization.
DRUG
IMPORTANCE
DRUG
IMPORTANCE
1997
COST
FORECAST
ACTIONS
1996
Ariflo (SB 207499): An oral phosphodiesterase 4 (PDE 4) inhibitor, Ariflo has the potential to
improve lung function and reduce symptoms in patients with COPD. An NDA is expected in 2001
or early 2002.
®
ANTIASTHMATICS
APPENDIX A
Albutrol Sulfate ($36.79)
20
0
®
APPENDIX B
Albuterol Inhaler ($25.95)
25
TRENDS IN
EXPENDITURES
TRENDS IN
EXPENDITURES
2000 PMPY = $15.40
INTRODUCTION
INTRODUCTION
12.7%
According to U.N. initiatives, manufacturers have until the end of 2005 to replace the propellant
chemicals in multi-dose inhalers (MDIs). These chemicals, called chlorofluorocarbons, are thought
to interact with the Earth’s ozone. New inhalers either use different propellants or deliver medications in a dry powder form.
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INTRODUCTION
FIGURE A13 THERAPY CLASS DRUG MARKET SHARE TREND
• Flovent® Diskus® (fluticasone) was approved for adults and for children as young as 4 years
old. Used once or twice a day to prevent asthma symptoms, the Diskus® device delivers a dry
powder formulation of Flovent®.
14.3%
2000 PMPY = $15.95
%
• The first combination corticosteroid and long-acting beta agonist product in the United States
was approved in August 2000. Advair® DiskusTM (fluticasone and salmeterol) is a dry-powder
formulation indicated for twice a day use to prevent asthma attacks in people who are 12 years
of age or older.
50
Zyrtec ($54.94)
40
Allegra ($57.13)
30
Generic ($4.74)
10
• An NDA that was filed in late 1999 for Asmanex® (mometasone inhalation powder) is still under
consideration by the FDA. It was approved by Canada in late 2000.
DRUG
IMPORTANCE
1996
1997
1998
1999
2000
• The rise in PMPY expenditures for the antihistamine class slowed to 14.3 percent to $15.95
in 2000. This rate of growth contrasts with the 38.5 percent PMPY rise between 1996 and 1997,
a 25.2 percent increase in 1998 and a 25.8 percent escalation in 1999. Unlike 1999 when the
cost increases were largely due to substantial increases in utilization, the 2000 growth was
about equally attributable to rises in utilization and per prescription costs. Most of the increase
in cost took place among the non-sedating antihistamines Claritin® and Allegra® and the lowsedating product Zyrtec®, which account for almost 90 percent of the market. All of these products have been promoted heavily through DTC advertising.
APPENDIX A
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
89
APPENDIX B
88
APPENDIX A
• The market share for Claritin®, the market leader, continued a decline seen in 1999, dropping
to a 42.5 percent share in 2000. The AWP per prescription for Claritin® was $71.93, an 8.3 percent rise over 1999 levels. With an average cost of $57.13 per prescription, 10.5 percent over
1999 costs, Allegra®’s market share rose to 23 percent in 2000. Zyrtec®, reached a 23.8 percent
market share in 2000. It had a 2000 AWP cost of $54.94, a 4.8 percent over 1999 costs.
ACTIONS
ACTIONS
Future Trends
Hismanal ($69.92)
20
DRUG
IMPORTANCE
• Yet another powdered form of an asthma drug was approved in February 2001. A beta agonist,
Foradil® AerolizerTM (formoterol inhalation powder) is indicated primarily for maintenance
therapy. It can also be taken for occasional prevention of exercise-induced bronchial spasms,
but it is not meant to relieve attacks.
Claritin ($71.93)
COST
FORECAST
• A new formulation of beclomethasone, QVAR® (beclomethasone HFA) has also been given FDA
approval. A new method allows QVAR® to be delivered in much smaller droplets than previous
inhalers were able to produce. As a result, the drug reaches more of the lungs — making
smaller doses effective. QVAR® is a controller drug.
60
0
APPENDIX B
% CHANGE IN PMPY COST
ANTIHISTAMINES
TRENDS IN
EXPENDITURES
TRENDS IN
EXPENDITURES
• Pulmicort® RespulesTM (budesonide inhalation suspension) became the first inhaled corticosteroid approved for children as young as 1 year of age. For use in a nebulizer, Pulmicort®
RespulesTM is given once or twice a day.
Although histamine is involved in many body functions, it is probably best known for its role in
the allergic response. Among other effects, histamine activity results in itchy, watery eyes, sneezing and rhinitis — the runny nose that often aggravates allergy sufferers. Antihistamines are
drugs that block the actions of histamine and lessen symptoms associated with allergy. Older
antihistamines such as Benadryl® (diphenhydramine) are good at blocking histamine, but they
also cause drowsiness in most people. Some older antihistamines are available without prescription, and some are even sold as OTC sleep aids. A major reason for the popularity of the newer
antihistamines — Claritin® (loratadine), Allegra® (fexofenadine) and Zyrtec® (cetirizine) — is
their much lower rates of sedation.
INTRODUCTION
COST
FORECAST
• Vanceril® and Beclovent®, the two brand-name products of an orally inhaled corticosteroid went
off patent in 1999. However, the FDA does not recognize the generic version of beclomethasone
dipropionate as therapeutically equivalent to the branded products. Both have market shares of
less than 2 percent.
ANTIHISTAMINES
PREFACE
PREFACE
• In 2000, Flovent® increased its market share to 10.4 percent from 7.1 percent in 1999.
In contrast, Pulmicort®’s market share increased from 1.1 percent to 1.6 percent.
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• In 2000 a new half-strength Allegra® tablet also received new indications for treating children.
The 30mg tablets are indicated for seasonal allergic rhinitis or chronic idiopathic urticaria that
affects children 6-12 years old.
(DECONGESTANT) NASAL STEROIDS
Allergy is an inflammatory disease of the upper airways. Nasal steroids are potent anti-inflammatory
agents. Because they are applied directly to swollen nasal tissue, they work quickly and they are not
absorbed to same the degree that oral steroids are, so side effects are minimal. Many have been formulated with non-irritating bases so they do not sting when sprayed onto inflamed tissue. As a class,
nasal steroids are generally less expensive to use than the newer non-sedating antihistamines.
PREFACE
PREFACE
• Claritin® syrup was granted approval for treating children as young as 2 years of age for
symptoms of both seasonal allergic rhinitis and chronic idiopathic urticaria (hives with no
apparent cause).
COST
FORECAST
• In the meantime, the FDA issued an Approvable letter for Clarinex® (desloratadine), a
metabolite of Claritin® intended to take its place in the brand name marketplace. Final approval
is on hold, however, due to deficiencies in production practices at some of the facilities that will
make Clarinex® and other drugs. No estimate is available for the release of Clarinex®.
• An NDA was submitted in the first quarter of 2001 for norastemizole, a refined form of
Hismanal® (astemizole). After FDA warnings about interactions and side effects, Hismanal®
was discontinued by the manufacturer in 1999.
40
Flonase ($54.94)
35
Nasonex ($53.80)
30
25
Rhinocort/Aqua ($45.47)
20
Nasacort AQ ($44.49)
15
Vancenase AQ ($56.82)
10
Beconase AQ ($46.59)
5
0
1996
1997
1998
1999
2000
• PMPY costs for nasal steroids rose by 7.4 percent to $6.85 in 2000. This rise is solely attributable to increased per prescription costs, as utilization actually declined by 1.4 percent in 2000.
• Nasal steroids include only branded products. The most commonly used products are Flonase®
(fluticasone), which increased its 2000 market share to 35.4 percent, and Nasonex® (mometasone), which captured a 20.1 percent market share in 2000. In contrast, market shares for other
products either grew marginally or declined.
• A new steroid nasal spray, Tri-Nasal® (triamcinolone), was approved in May 2000 for treatment
of allergic rhinitis in patients as young as 12 years old. It will be dosed once a day.
ACTIONS
ACTIONS
%
DRUG
IMPORTANCE
• Last June, an NDA was submitted for Xolair® (olizumab), a humanized monoclonal antibody that
interferes with the action of immunoglobulin E (IgE). IgE is a substance produced in the body to
help mediate the response to asthma triggers. Although trials were initially delayed by concerns
over possible side effects, Xolair® is now being considered for use in people who have both
asthma and seasonal allergies. It will have to be injected in a physician’s office — probably
once or twice a month.
7.4%
2000 PMPY = $6.85
COST
FORECAST
DRUG
IMPORTANCE
• Tentative approval for loratadine tablets and syrup, the generic version of Claritin® was given
in January 2001. Even though the extended Claritin® patent will not expire until December 2002,
Claritin®’s manufacturer has filed patent-infringement lawsuits to further delay the introduction
of a generic.
% CHANGE IN PMPY COST
TRENDS IN
EXPENDITURES
TRENDS IN
EXPENDITURES
Future Trends
(DECONGESTANT) NASAL STEROIDS
INTRODUCTION
INTRODUCTION
FIGURE A14 THERAPY CLASS DRUG MARKET SHARE TREND
• An intranasal antihistamine, Astelin® (azelastine), which was already approved for
rhinitis caused by seasonal allergies, now has an additional indication for non-allergic
or vasomotor rhinitis.
COUGH AND COLD
APPENDIX A
APPENDIX B
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
91
APPENDIX B
90
APPENDIX A
A multitude of drugs aim to relieve symptoms of the common cold and other upper respiratory
conditions. Antihistamine-decongestant combinations make up the majority of cough and cold
products that require a prescription. Decongestants such as pseudoephedrine and phenylephrine
constrict blood vessels to reduce swelling in nasal tissue, a symptom that often accompanies
allergies or colds. Oral decongestants may also act as a stimulant, so they help to counteract
any sedation that the antihistamine may cause. Since they are absorbed into the blood, however,
oral decongestants can affect blood vessels throughout the body — potentially worsening conditions like hypertension.
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In November 2000, the FDA advised manufacturers to discontinue prescription and OTC products
that contained phenylpropanolamine. Widely used as a decongestant, phenylpropanolamine
was also the main ingredient in many non-prescription weight loss products. The FDA’s action
followed published reports of hemorrhagic strokes — mainly in women — associated with the
use of phenylpropanolamine.
% CHANGE IN PMPY COST
5.6%
2000 PMPY = $9.54
%
60
Generic ($12.22)
Claritin-D 12 Hour ($69.96)
40
Allegra-D ($54.58)
30
Entex LA ($40.52)
20
0
1996
1997
1998
1999
2000
• The manufacturer of Claritin® (loratadine) has filed lawsuits against at least two generic
companies that have submitted applications to the FDA for approval of a generic. A generic
version of Claritin®-D cannot be released until the lawsuits are settled.
• Zyrtec®-D (cetirizine and pseudoephedrine) received an Approvable letter from the FDA
in late 2000.
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
93
APPENDIX B
92
APPENDIX A
ACTIONS
APPENDIX A
Future Trends
Prescribing antibiotics for non-bacterial infections is often cited as a reason for the increase
in bacterial resistance that has been seen in recent years. Patients contribute to the spread of
resistance by requesting antibiotics for a cold or the flu — which are not caused by bacteria —
and by failing to take antibiotics as prescribed. Ironically, the attempt to avoid bacterial
contamination by using antibacterial cleaners and soaps is also adding to the problem.
Moreover, extensive use of antibiotics for crops and livestock increases bacterial resistance.
Government agencies in several countries — including the United States — have taken
measures to ban or limit antibiotic use in agriculture. Regulating human use of antibiotics
and monitoring bacterial resistance patterns are among other ways that countries around the
world are trying to cope with the problem.
ACTIONS
• Despite a 5 percentage point drop in market share, over half of this class consists of generic
products. Claritin®-D (loratadine and pseudoephedrine), a branded combination product that
includes a non-sedating antihistamine, made up 18.2 percent of the 2000 market. The only
other branded combination product of any importance in this class, Allegra®-D (fexofenadine
and pseudoephedrine), saw its market share continue to increase to 8.5 percent in 2000.
Whereas the average AWP cost per prescription is $12.22 for generic products (an increase
of 16.9 percent over 1999 levels), it is $69.96 for Claritin®-D and $54.58 for Allegra®-D.
AWP prescription costs grew by 10 percent for both of these branded products.
Antibiotic resistance is an increasingly critical global issue. Bacteria develop immunity when
antibiotics are used improperly. Many types of bacteria contain a small number of cells with
genes that are resistant to certain antibiotics. When exposed to the antibiotic, all the non-resistant bacteria are killed or inhibited. Resistant bacterial cells survive to multiply, passing down
their resistance to new generations of bacteria.
DRUG
IMPORTANCE
DRUG
IMPORTANCE
• PMPY costs for cough and cold products grew by a modest 5.6 percent to $9.54 in 2000, despite
an almost 10 percent decline in PMPY utilization.
Bacteria are one large group of infection-causing micro-organisms. Commonly used antibacterial
drugs — often called antibiotics — include cephalosporins, macrolides, penicillins, quinolones
and tetracycline. Several other classes are used only for certain types of infections because of their
specific effectiveness or in hospitals due to significant side-effect potential.
COST
FORECAST
COST
FORECAST
10
TRENDS IN
EXPENDITURES
TRENDS IN
EXPENDITURES
50
Once thought to be on the threshold of containment, if not elimination, infectious diseases
represent the second leading cause of death in the world. According to the World Health
Organization, over 11.5 million lives were lost in 1999 to the five most deadly types of infection
— acute lower respiratory infections, AIDS, tuberculosis, malaria and infectious diarrhea.
Previously unknown infectious agents are emerging (Ebola), others that were relatively mild have
become more deadly (West Nile Virus) and ones thought to be under control are re-appearing
(tuberculosis, foot and mouth disease). A growing concern in some countries is the threat of
bioterrorism using infective agents.
INTRODUCTION
INTRODUCTION
COUGH/COLD
Infections occur when micro-organisms invade living tissue, then multiply and cause damage.
A number of different organisms can be infective — bacteria, viruses and fungi are among the
most common. More uncommon in the United States, but important in other parts of the world,
are infectious diseases caused by micro-organisms such as protozoa (malaria, sleeping sickness),
other parasites (giardiasis) and prions (bovine spongiform encephalopathy or Mad Cow Disease).
Some experts in the control of infectious diseases suggest that increased intercontinental travel,
faster shipping of containerized freight and global warming may spread some relatively rare
infections into areas where little or no immunity exists among the local population.
PREFACE
PREFACE
ANTI-INFECTIVES
FIGURE A15 THERAPY CLASS DRUG MARKET SHARE TREND
APPENDIX B
TABLE OF
CONTENTS
TABLE OF
CONTENTS
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PREFACE
INTRODUCTION
TRENDS IN
EXPENDITURES
COST
FORECAST
NeisVac-C® will protect against group C meningococcal infection. Already approved in Britain,
this vaccine can be used for children as young as 1 year old.
• A new vaccine that came to market is Prevnar® (pneumococcal 7-valent conjugate vaccine)
for the prevention of pneumonia in high-risk infants.
Fungi are tiny plants that can infect humans and animals. Many infections caused by fungi are
superficial — they do not invade tissue but remain primarily on the surface of the skin or mucous
membranes. Usually slow growing, minimally invasive fungal infections often affect areas like
toenail beds that have a poor blood supply. Both topical and systemic drugs may be needed to
eliminate them and therapy may take several months or longer. When fungal infections are systemic — most often in people whose immune systems are damaged by other conditions or drug
therapies — they can be life-threatening.
The following antibiotics are among those in clinical trials:
• Still under FDA review is an NDA that was filed in March 2000 for Ketek® (telithromycin).
Ketek® is the first agent in a new class of antibiotics called ketolides, which are derived from
macrolides. Ketek® has been studied for several respiratory infections, but in April 2001 an
FDA committee recommended its approval only for serious community-acquired pneumonia
in adults.
• In January 2001, the FDA approved Cancidas® (caspofungin acetate), the first in a new class
of antifungal drugs called echinocandins or glucan synthesis inhibitors. Cancidas® will be used
mostly in hospitals for the treatment of a particularly serious fungal infection, aspergillosis, in
patients who have not been helped by other antifungal therapies.
• An NDA may be submitted this year for Vfend® (voriconazole), another agent in late stages of
clinical trials for serious systemic fungal infections.
DRUG
IMPORTANCE
• Results from a Phase III study for Neuprex® (opebecan), rBPI-21 in the treatment of children
with severe meningococcemia were not conclusive enough for the FDA to accept an application
for full approval. A member of a new antibiotic class called bactericidal/permeability increasing
proteins, Neuprex® does have orphan status for meningococcemia. Trials for its use in other
serious infections continue.
StreptAvax® is being tested against several types of Streptococcus group A that cause throat
and skin infections.
• Rifaximin is a broad-spectrum antibiotic derived from rifamycin and designed to be active in
the GI tract. It is an orphan drug for the treatment of hepatic encephalopathy, and it is also in
clinical trials for treating lower GI infections.
ACTIONS
• A member of a new antibiotic class, CidecinTM (daptomycin) for injection appears to have
effectiveness against several resistant bacteria. It is in clinical trials for skin and soft tissue
infections, community-acquired pneumonia, complicated urinary tract infections and bacteremia.
95
APPENDIX B
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
APPENDIX A
• Also in various stages of clinical trials for several different anti-infective indications is ramoplanin, which has shown activity against resistant micro-organisms. Both oral and topical
forms are being developed as potential ways to prevent the spread of infections in hospitals.
94
COST
FORECAST
DRUG
IMPORTANCE
• Malarone® (atovaquone and proguanil), a new preventative and treatment for malaria,
was introduced.
Campyvax® is an oral vaccine being developed to prevent GI infections caused by
Campylobacter bacteria.
TRENDS IN
EXPENDITURES
ACTIONS
Vaccines for some bacterial infections are also in development. Among them:
INTRODUCTION
APPENDIX A
Partially in response to antibiotic resistance, drug manufacturers are trying to discover new
antibiotics or improve older ones. The last few years have seen at least two completely new classes of antibacterial drugs — oxazolidinones and streptogramins — approved by the FDA. The first
oxazolidinone to be approved in the United States, Zyvox® (linezolid), is effective against some
bacteria that resist current therapies. Zyvox® will be used mainly in hospitals, but its use may
shorten hospital stays and also lessen the need for outpatient intravenous antibiotics.
Additionally, in 2000:
PREFACE
APPENDIX B
TABLE OF
CONTENTS
TABLE OF
CONTENTS
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TABLE OF
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Cephalosporins are a group of bactericidal antibiotics that are very similar to penicillins in
structure. Usually described as belonging to one of four generations according to which specific
bacteria they eliminate, the cephalosporins are broad-spectrum antibiotics — meaning they have
good general activity against many bacterial types.
• According to the FDA Orange Book, patent protection for Suprax® and Vantin® has expired.
No generic versions have been introduced, however. Generics are now available for Duricef®
(cefadroxil) and for two cephalosporins that are mainly used in hospitals — Fortaz®/Tazicef®
(ceftazidime) and Mefoxin® (cefoxitin).
PREFACE
PREFACE
CEPHALOSPORINS
Future Trends
FIGURE A16 THERAPY CLASS DRUG MARKET SHARE TREND
% CHANGE IN PMPY COST
–9.4%
2000 PMPY = $6.94
%
MACROLIDES
50
Cephalexin ($28.64)
Cefzil ($68.35)
40
Macrolides are generally bacteriostatic; they inhibit bacterial replication rather than killing
bacteria outright. Although macrolides are chemically different from penicillins, both of these
antibiotic classes are effective against many of the same bacteria.
TRENDS IN
EXPENDITURES
TRENDS IN
EXPENDITURES
INTRODUCTION
INTRODUCTION
CEPHALOSPORINS
• An NDA that was submitted in late 1999 for Spectracef® (cefditoren pivoxil) is still pending.
Spectracef® would be a new oral cephalosporin for the treatment of respiratory infections
in adults.
Ceftin ($92.31)
30
Cefaclor ($60.55)
FIGURE A17 THERAPY CLASS DRUG MARKET SHARE TREND
MACROLIDES
20
% CHANGE IN PMPY COST
Suprax ($62.59)
10
–2.1%
2000 PMPY = $8.01
Ceclor/CD ($72.08)
%
1996
1997
1998
1999
2000
DRUG
IMPORTANCE
• The market share for generic cephalexin rose from 45.8 percent in 1999 to 49.6 percent in
2000. The market share for virtually all other products in this class either declined or remained
virtually flat.
• The use of another generic, cefaclor, (often used to treat otitis media) continued to decline from
a peak of 14.5 percent in 1996 to 5.3 percent in 2000 owing to the availability of more effective
second-line antibiotics.
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
40
E-Mycin ($16.27)
30
PCE ($54.51)
20
10
0
1996
1997
1998
1999
2000
• After rising by 19 percent in 1999, the overall rate of growth in PMPY cost for macrolides
declined by 2.1 percent to $8.01 in 2000. This reduction is solely a function of the 7.4 percent
decline in utilization of these products.
• Zithromax® (azithromycin), Biaxin® (clarithromycin) and generic macrolides account for about
91.9 percent of all drug use in this category. Zithromax® dominates this therapy class, growing
its market share to 61.6 percent in 2000. This increased market share came at the expense of
both generic erythromycins, which continued to decline from a 26.7 percent market share in
1996 to 13.8 percent in 2000, and Biaxin® whose market share declined from a peak 34.6 percent in 1996 to 16.5 percent in 2000. While losing substantial market share, the average cost
of a generic prescription in this class rose 22.1 percent; in contrast, the average cost per
prescription for Zithromax® and Biaxin® rose 3.7 percent and 10.5 percent, respectively.
97
APPENDIX B
96
Generic ($21.21)
APPENDIX A
• The preference for two second generation branded cephalosporins, Cefzil® (cefprozil) and
Ceftin® (cefuroxime), declined in 2000. The market share for Cefzil® dropped to 14.8 percent,
while the share for Ceftin® decreased to 13.2 percent. Third-generation cephalosporins, Suprax®
(cefixime), Vantin® (cefpodoxime) and Cedax® (ceftibuten), have relatively low use, which seems
to be declining. Omnicef ® (cefdinir), a third-generation cephalosporin introduced to the U.S.
market in October 1998, offered nothing new to the already crowded class but still managed
continued growth in market share from 0.3 percent in 1998 to 2.2 percent in 2000.
50
ACTIONS
ACTIONS
Biaxin/XL ($73.35)
60
DRUG
IMPORTANCE
APPENDIX A
Zithromax ($39.57)
70
• PMPY expenditures for cephalosporins declined by a substantial 9.4 percent to $6.94 in 2000.
This decline was primarily due to the 11.3 decrease in utilization of these products.
APPENDIX B
80
COST
FORECAST
COST
FORECAST
0
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PENICILLINS
Future Trends
The most widely used antibiotics in the world, penicillins kill bacteria by destroying their cell
walls. Only a few penicillins do not have generic equivalents.
• In December 2000, the FDA issued a Non-Approvable letter to the maker of Factive®
(gemifloxacin). Originally submitted for use in respiratory and urinary infections, Factive®
may go into additional trials if the FDA requests further clinical information.
FIGURE A18 THERAPY CLASS DRUG MARKET SHARE TREND
PENICILLINS
% CHANGE IN PMPY COST
2000 PMPY = $7.39
ANTIVIRALS
%
100
Generic ($8.02)
80
Augmentin ($80.89)
40
• Generics continue to dominate this class despite seeing a market share decline to 69.2 percent
in 2000.
FIGURE A19 THERAPY CLASS DRUG MARKET SHARE TREND
COST
FORECAST
1996
1997
1998
1999
2000
ANTIVIRALS
• Although Augmentin® now has generic equivalents in many parts of Europe, its American
patent, due to expire in 2002, has been extended to 2015.
–2.6%
2000 PMPY = $10.02
%
30
Valtrex ($XXX.XX)
25
Famvir ($XX.XX)
20
Tamiflu ($XXX.XX)
15
Zerit ($302.55)
10
Epivir ($267.13)
Crixivan ($426.09)
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
1997
1998
1999
2000
99
APPENDIX B
98
1996
APPENDIX A
APPENDIX A
5
0
ACTIONS
• Generic approval has been given for 500mg and 850mg strengths of amoxicillin.
% CHANGE IN PMPY COST
DRUG
IMPORTANCE
• Augmentin® (amoxicillin and sodium clavulanate) and Amoxil® (amoxicillin) are the only
branded products in this class with significant use, with market shares of 23.3 and 7.4 percent,
respectively. The average prescription price for Augmentin® grew by 11.2 percent to $80.89 in
2000 compared with the 2.4 percent rise to a $8.02 average price for generic products and the
decrease of 9.8 percent to $14.82 for Amoxil®.
COST
FORECAST
• PMPY costs of penicillins rose 8.9 percent in 2000, despite a 5.1 percent decline in utilization.
The AIDS crisis has sparked intensive research — which, in turn, has lead to new treatments
for several viral illnesses. Although no cure or prevention has yet been discovered for human
immunodeficiency virus (HIV), the micro-organism that causes AIDS, scientists are finding better
ways to treat it as well as other viral illnesses such as hepatitis and flu. Multiple-drug therapy
helps manage resistance. In addition, manufacturers are developing combination products and
controlled release dosage forms not only to help control viral resistance, but also to encourage
patient compliance — a critical factor in controlling the progression of viral conditions.
20
0
DRUG
IMPORTANCE
Viruses are much smaller than bacteria or fungi. Relatively simple micro-organisms that cannot
reproduce alone, they must take over the reproductive systems in living host cells to multiply.
Drugs that kill viral cells may also destroy or damage host cells. Making them even more difficult
to treat, viruses can mutate rapidly causing drugs to lose their effectiveness. Treatment for viral
infections is often challenging. AIDS patients, for example, may have to remember complicated
dosing schedules for multiple doses of several different drugs.
TRENDS IN
EXPENDITURES
TRENDS IN
EXPENDITURES
60
ACTIONS
• Injectable Floxin® (ofloxacin) patents expire in September 2001, but the oral form is still
protected until 2003. Cipro® is also under patent until 2003.
INTRODUCTION
INTRODUCTION
8.9%
APPENDIX B
PREFACE
PREFACE
TABLE OF
CONTENTS
TABLE OF
CONTENTS
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TABLE OF
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TABLE OF
CONTENTS
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INTRODUCTION
• Drugs for viral illnesses other than HIV/AIDS now dominate the antivirals class, which in previous
years consisted almost entirely of drugs to treat HIV. Partly due to the rapidly increasing number
of drugs being approved for HIV and the multiple drug regimens needed to treat HIV as well as
to newly available drug therapies for previously untreatable viruses such as flu; no one HIV drug
now emerges to lead the class.
• Tamiflu® (oseltamivir) captured 4.9 percent of the market in 2000.
DRUG
IMPORTANCE
ACTIONS
• In September 2000, the FDA gave accelerated approval to Kaletra® (lopinavir and ritonavir),
a combination of two protease inhibitors. Currently, it is the only drug of its kind that can be
used for adults and children as young as six months old for the treatment of HIV infection.
Even though it simplifies the complex dosing required for many AIDS patients, Kaletra®
must still be taken with other antiviral drugs.
• A second combination product — consisting of three nucleoside reverse transcriptase inhibitors
— was approved late last year. Trizivir® (abacavir, lamivudine and zidovudine) is intended to be
taken twice a day by adults and adolescents with HIV.
• The FDA has also approved a new enteric-coated, delayed-release formulation of Videx®
(didanosine). Called Videx® EC, the new dosage form disintegrates in the small intestine.
It is taken once a day.
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
• Ampligen represents another new class of antivirals called nucleic acid compounds. They are
designed to activate the immune system against viruses. Ampligen has entered Phase III trials
for treating chronic fatigue syndrome and Phase II trials for AIDS, hepatitis B and hepatitis C.
• Development of Preveon® (adefovir dipivoxil) for treating AIDS was discontinued after an
FDA advisory panel recommended against its approval. A lower dose is in Phase III trials for
hepatitis B, however.
• In November, the FDA gave Fast Track designation to development of tipranavir, a protease
inhibitor in Phase III trials for treating AIDS. Slightly different in structure from other protease
inhibitors, tipranavir may be used for patients whose infections have become resistant to other
drug therapy.
101
APPENDIX B
100
• Results from Phase II trials of T-20, the most advanced agent in the new fusion inhibitor class,
were presented in early 2001. Fusion inhibitors prevent viruses from attaching to host cells thus
blocking viral entry. In both adult and pediatric AIDS patients, T-20 showed good results as
monotherapy or in combination with other antiviral agents. T-20 has been given Fast Track
status by the FDA. A second fusion inhibitor, T-1249, is also showing good results in earlier
phases of investigation.
APPENDIX A
APPENDIX A
• In an almost complete reversal of previous recommendations that called for early, aggressive
treatment of HIV, guideline updates released in February 2001 advocate delaying the start of
therapy for asymptomatic HIV infection in adults and adolescents until immune function begins
to decline. Concerns over long-term side effects of treatment led the Panel on Clinical Practices
for the Treatment of HIV Infection to the suggested therapy changes.
• Although Picovir® (pleconaril) — an investigational agent that held initial promise in treating
common cold viruses — has been disappointing in clinical trials, an NDA will likely be filed for
its use against colds. Phase III clinical trials for Picovir® in the treatment of viral meningitis
and viral respiratory infection are in late stages.
ACTIONS
APPENDIX B
• Among the protease inhibitors, Crixivan (indinavir) continued to experience a slight market
share decline to 1.4 percent, while the market share for Norvir® (ritonavir) remained under
1 percent.
Future Trends
DRUG
IMPORTANCE
®
• In December, an NDA for the separate marketing of Rebetol® (ribavirin) was submitted. Rebetol®
capsules have been available in the United States since 1998, but only packaged as Rebetron®
— a kit that includes Intron-A® (interferon alfa-2b), an injected drug. Rebetol® will be indicated
for treating hepatitis C.
COST
FORECAST
COST
FORECAST
• The market shares for Epivir® (lamivudine) and Zerit® (stavudine) continued to drop to
2.7 percent and 3 percent, respectively, in 2000.
• Peg-Intron® (peginterferon alfa-2b) was approved in early 2001 for the treatment of some
patients with chronic hepatitis C. A second pegylated interferon, Pegasys® (pegylated interferon
alfa 2a), is pending FDA approval also for chronic hepatitis C in certain patients. Pegylation is
a way of attaching active drug molecules to inactive molecules of polyethylene glycol (PEG).
The combined result stays in the blood longer meaning that pegylated interferons need to
be injected only once a week instead of the three or more times a week that unpegylated
interferons must be used.
TRENDS IN
EXPENDITURES
• Valtrex® (valacyclovir) and Famvir® (famciclovir), used to treat herpes, are the most widely used
branded products in this category with a growing combined 36.3 percent market share in 2000.
• Approval for an orphan indication was given to Veldona® (interferon-alpha), an oral lozenge for
treating AIDS patients who have oral warts caused by papillomavirus.
INTRODUCTION
TRENDS IN
EXPENDITURES
• After growing dramatically between 1997 and 1998, the market share for generics continued to
decline to 28.4 percent in 2000.
• In January 2001, Tamiflu®, which now has an oral suspension dosage form for children as young
as 12 months, received additional FDA approval for flu prevention.
PREFACE
PREFACE
• After growing at a faster rate, 39.9 percent, than any other class of drug in 1999, PMPY costs
for antivirals declined by 2.6 percent to $10.02 in 2000. Both the utilization and per prescription costs of those products changed very little from 1999 levels.
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W O M E N ’ S H E A LT H
• Valcyte® (valganciclovir) had been approved for treating cytomegalovirus (CMV) retinitis in AIDS
patients. An adaptation of the drug ganciclovir, Valcyte® was developed as an oral dosage form.
• A number of viral vaccines are in late stages of development including:
Twinrix® (inactivated hepatitis A and recombinant hepatitis B vaccine). A biological
license application (BLA) has been approved for this combination vaccine that reduces
the number of injections needed to prevent two strains of hepatitis in individuals at high
risk of exposure.
DRUG
IMPORTANCE
• An NDA has been filed for FDA review of Xyvion® (tibolone) in the treatment of osteoporosis.
A tissue specific steroid, Xyvion® exhibits estrogen-like protective effects on bone and other
tissues without producing adverse effects on breast or endometrial tissues. Xyvion® is licensed
under a number of brand names in countries where it is already approved.
• Priority review status has been given to the NDA for Aslera® (prasterone or dehydroepiandrosterone [DHEA]) that was submitted in October 2000. An indication is being sought for the oral
treatment for women with mild to moderate systemic lupus erythematosus (SLE). In general,
SLE patients have abnormally low levels of prasterone, a naturally occurring intermediary in the
conversion of cholesterol to sex steroids. Already designated as an orphan drug, Aslera® has
been shown in clinical trials not only to improve SLE symptoms, but also to reduce the need for
corticosteroid drugs.
ACTIONS
ACTIONS
• An NDA was submitted in January 2001 for the first contraceptive patch, Ortho Evra® (ethinyl
estradiol and norelgestromin transdermal system). If approved, one Ortho Evra® patch would be
worn continuously for seven days. For one week each month, women who use Ortho Evra® would
not wear a patch.
DRUG
IMPORTANCE
Arilvax® (live-attenuated yellow fever vaccine). Already available in Europe and Asia,
Arilvax® has finished U.S. trials and an NDA for its approval may be filed as early as
mid-2001. Vaccination against yellow fever is recommended for U.S. military personnel
and civilian travelers who may be visiting areas where yellow fever is still common.
• For women who want long-term contraception, the FDA has approved Mirena® (levonorgestrelreleasing intrauterine system). Once inserted, Mirena® can prevent pregnancy for up to
five years.
COST
FORECAST
COST
FORECAST
The BLA for Flumist®, a nasal vaccine for influenza prevention, is currently under review
by the FDA. Approval is possible later this year — in time for the 2001-2002 flu season.
• A contraceptive injection, Lunelle® (estradiol and medroxyprogesterone), was approved by the
FDA in 2000. Administered only once a month, Lunelle® was designed to be more convenient
than oral contraceptives and more flexible than other injections or implants.
TRENDS IN
EXPENDITURES
• In January 2001, the FDA issued a Non-Approvable letter in response to an NDA submitted for
Ceplene® (histamine dihydrochloride) in treating metastatic melanoma. The manufacturer will
do additional research for that indication while trials for other indications, including hepatitis
C, are also continuing.
• In September women using Norplant® (levonorgestrel implants) were advised to use additional
non-hormonal forms of contraception. Systems inserted since October 20, 1999, may not release
enough levonorgestrel to be effective.
INTRODUCTION
INTRODUCTION
• Further studies have begun for Coactinon® (emivirine) in the treatment of HIV. In 1999, the FDA
denied an NDA submitted for its approval on the grounds that more clinical information was
needed. Coactinon® is a non-nucleoside reverse transcriptase inhibitor.
Although women experience the same general health problems that men do, they also have
special health needs that center on reproduction. Many younger women control fertility through
the use of contraceptive or fertility enhancing drugs. After menopause, women may use supplemental hormones or miscellaneous endocrine drugs to relieve menopausal symptoms and
preserve bone mass.
PREFACE
PREFACE
• Coviracil® (emtricitabine) is a once-daily nucleoside analog under investigation for HIV, AIDS
and hepatitis B treatment. Some Phase III trials have been completed for its effectiveness in
combination with other antiviral agents.
TRENDS IN
EXPENDITURES
TABLE OF
CONTENTS
TABLE OF
CONTENTS
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ORAL CONTRACEPTIVES
APPENDIX A
APPENDIX B
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
103
APPENDIX B
102
APPENDIX A
Introduced in the 1960s, oral contraceptives (OCs) became the first class of drugs developed not
to treat an illness but to improve the quality of life. Still perceived by some as lifestyle drugs, OCs
are generally accepted throughout the world as one of the most significant social and medical
developments of the 20th century.
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PREFACE
As formulations and combinations have changed, many of the adverse effects associated with the
use of early OCs have been reduced or eliminated. Some women may experience side effects like
nausea, headache, breast tenderness, weight gain, irregular bleeding and depression, especially
when beginning to take OCs. Women who smoke or who have certain medical conditions such as
breast cancer should use them only with caution. OCs cannot prevent sexually transmitted diseases. On the plus side, OC use is associated with lower incidences of ectopic pregnancy, pelvic
inflammatory disease, iron-deficiency anemia and cancers of the endometrium and ovaries. They
are also commonly used to regulate the menstrual cycle.
ORAL CONTRACEPTIVES
% CHANGE IN PMPY COST
1.7%
2000 PMPY = $9.34
Ortho Tri-Cyclen ($33.31)
20
Generic ($28.69)
Ortho-Novum ($33.31)
15
Triphasil-28 ($32.40)
DRUG
IMPORTANCE
ACTIONS
1997
1998
1999
Future Trends
Ortho-Cept ($33.67)
• Tri-Norinyl® (ethinyl estradiol and norethindrone) is scheduled to lose patent protection in
August 2001.
2000
• Because of the 3.5 percent decline in utilization, the overall PMPY costs for oral contraceptives
grew by only 1.7 percent in 2000.
• Even though many are available generically, overall use of the estrogen-progestin combinations
is declining. The Ortho-Novum® product line, for example, continued its market share decline,
dropping from 17.3 percent in 1997 to 9.8 percent in 2000. Market share for generic versions of
the most popular branded combinations increased substantially from 8.1 percent in 1999 to
13.6 percent in 2000. Sustained growth has been seen with some newer products and formulations. Most notably, Ortho Tri-Cyclen® (ethinyl estradiol and norgestimate) increased its market
share from 12.2 percent in 1998 to 16.8 percent in 1999 to 21 percent in 2000.
At menopause, the amounts of female hormones that are produced naturally drop. Aggravating
but relatively short-term effects of hormone loss, such as hot flashes and mood swings, are
greatly overshadowed by the increased risk of heart disease, stroke and osteoporosis faced by
older women. Artificial replacement of the hormones — estrogens and progestins — alleviates
menopause symptoms. More importantly, when taken for longer periods of time, hormone replacement therapy (HRT) can delay the progression of osteoporosis and lower cholesterol levels. It may
help to protect against heart disease and may even help to preserve memory.
105
APPENDIX B
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
ESTROGENS
APPENDIX A
• Long awaited approval was granted for Mifeprex® (mifepristone) in September 2000. Formerly
known as RU-486, the controversial tablet is indicated in combination with misoprostol for the
termination of pregnancy up to seven weeks. It will be distributed only to clinics or physicians’
offices where it will be administered.
• The manufacturers of the emergency contraceptive tablet, Plan B® (levonorgestrel) have
requested a change to OTC status from the FDA. Studies of the product’s directions as well
as its use will have to be conducted before approval is considered. Washington State already
allows pharmacies to sell emergency contraception without a prescription and similar legislation is pending in Virginia.
ACTIONS
APPENDIX A
1996
Desogen ($28.50)
DRUG
IMPORTANCE
APPENDIX B
Lo/Ovral-28 ($34.53)
5
104
• In January 2001, the manufacturer of Alesse® (ethinyl estradiol and levonorgestrel) submitted
an NDA for an additional indication in the treatment of acne. Approved in 1997 for oral contraception, Alesse® is a biphasic tablet containing low amounts of both estrogen (20 mcg of
ethinyl estradiol) and progestin (100mcg of levonorgestrel).
COST
FORECAST
COST
FORECAST
10
0
• Generic versions of Ortho-Novum® 1/35 (ethinyl estradiol and norethindrone) and Modicon® 28
(ethinyl estradiol and norethindrone) were approved in March 2001. Both new generics will be
introduced during fourth quarter 2001 under the name Nortrel®. Tentative approval has also
been granted for a Nortrel® generic of Ortho-Novum® 7/7/7 (ethinyl estradiol and norethindrone).
Final FDA approval for the generic, also to be launched with the Nortrel® name, will depend on
the outcome of a patent challenge by the generic manufacturer.
TRENDS IN
EXPENDITURES
TRENDS IN
EXPENDITURES
%
25
• The FDA has approved generic equivalents for the oral contraceptives Loestrin® and Loestrin®
FE. To be marketed as Microgestin® and Microgestin® FE, the new products contain ethinyl
estradiol and norethindrone. Microgestin® FE also contains ferrous fumarate.
INTRODUCTION
FIGURE A20 THERAPY CLASS DRUG MARKET SHARE TREND
• Cyclessa® (ethinyl estradiol and desogestrel) contraceptive tablets received FDA approval in
December 2000. Cyclessa® provides only 25mcg of ethinyl estradiol per tablet — which is
at least 10mcg per tablet less than other triphasic oral contraceptives marketed in the
United States.
PREFACE
INTRODUCTION
TABLE OF
CONTENTS
TABLE OF
CONTENTS
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In the Women’s Health Initiative (WHI), a slightly increased risk of stroke was observed during
the first year of HRT. ERA and WHI are continuing to examine the long-term effectiveness of HRT
in women who have not developed heart disease. Until evidence that is more conclusive is
presented, the National Heart, Lung and Blood Institute states that the benefits of HRT outweigh
its risks and that women should consult with their doctors to individualize the management
of menopause.
ESTROGENS
% CHANGE IN PMPY COST
12.4%
• A tablet form combining the estrogens in Premarin® and a progestin called trimegestone is
in late stage development for relief of menopausal symptoms. Another combination, estradiol
and trimegestone, is also being investigated for treating side effects of menopause and
for osteoporosis.
• HRT products containing lower doses of estrogen and progestin are in late stage clinical
trials. Low-dose estrogen can prevent postmenopausal bone loss with fewer side effects
than higher-dose products.
MISCELLANEOUS ENDOCRINES
PREFACE
60
Premarin ($23.80)
Prempro ($31.00)
40
Generic ($15.38)
30
Estrace ($21.09)
20
Ogen ($33.06)
10
Estraderm ($29.63)
FIGURE A22 THERAPY CLASS DRUG MARKET SHARE TREND
MISCELLANEOUS ENDOCRINES
0
1996
1997
1998
1999
DRUG
IMPORTANCE
50
Hormones produced by the endocrine glands regulate metabolism, reproduction and other body
functions. Thyroid diseases, growth hormone deficiencies, infertility and osteoporosis are all
among the many disorders that can be caused by imbalances of endocrine hormones. Recently,
a number of new treatments have become available for endocrine conditions. Among the most
widely used are bisphosphonates and selective estrogen receptor modulators (SERMs) to prevent
or treat osteoporosis.
% CHANGE IN PMPY COST
2000
COST
FORECAST
COST
FORECAST
Future Trends
2000 PMPY = $10.79
%
DRUG
IMPORTANCE
• In addition to previous indications for hormone replacement, Vivelle® (estradiol transdermal
system) has been approved for the prevention of postmenopausal osteoporosis. At the same
time, the FDA approved a lower strength 0.025mg per day Vivelle® patch.
TRENDS IN
EXPENDITURES
FIGURE A21 THERAPY CLASS DRUG MARKET SHARE TREND
• Activella® (estradiol and norethindrone) tablets were approved in April 2000 for the prevention
of osteoporosis and other symptoms associated with menopause. Under the brand name
Activelle®, the product had already been approved for HRT.
INTRODUCTION
INTRODUCTION
In the past few years, preliminary results from large ongoing studies of women receiving HRT
seemed to dispute its positive cardiovascular effects. The Heart and Estrogen/Progestin
Replacement Study (HERS) found that short-term use of HRT neither reduced the risk of death
from coronary heart disease nor prevented further heart attacks in postmenopausal women with a
history of heart disease. The Estrogen Replacement and Atherosclerosis (ERA) Trial found that HRT
did not prevent progression of atherosclerosis in women with established coronary artery disease.
PREFACE
TRENDS IN
EXPENDITURES
TABLE OF
CONTENTS
TABLE OF
CONTENTS
22501_appA
29.8%
2000 PMPY = $6.89
APPENDIX A
• Premarin (conjugated estrogens) and Prempro (conjugated estrogens and medroxyprogesterone
fixed-dose tablets) dominate this class with a combined 64.9 percent market share. However,
Premarin® continued its dramatic decline in market share, dropping from 71.8 percent in 1994
to 42.3 percent in 2000. The market share for Prempro® remained basically flat at 22.6 percent
in 2000. The average per prescription costs of these two products rose 14.7 percent and 18.3
percent, respectively in 2000.
40
Miacalcin ($66.98)
30
DDAVP ($164.14)
®
®
Fosamax ($69.49)
50
Evista ($71.06)
20
APPENDIX A
10
0
1996
1997
1998
1999
2000
• Branded products that contain several types of estrogen have dominated the market, mainly
because bioequivalence cannot be documented for some generics. Generics currently have a
growing but relatively small 10.5 percent market share.
106
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
107
APPENDIX B
APPENDIX B
60
ACTIONS
ACTIONS
%
• PMPY costs for estrogens grew by 12.4 percent in 2000. This growth rate is attributable solely to
the increase in the average cost per prescription, as utilization declined by 2.6 percent.
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D E R M AT O L O G I C A L S
• Fosamax® (alendronate) and Evista® (raloxifene) dominate this class with a combined almost
three-quarter market share. Evista®’s market share grew dramatically from 15 percent in 1998
to 30.1 percent in 2000, while the market share for Fosamax® declined from 47.9 percent in
1998 to 42.3 percent in 2000.
Infections, burns and symptoms of systemic conditions are only a few of the conditions that
can affect the skin. Most of the drugs used to treat skin problems are applied locally to the skin
surface. Not only does the drug reach the affected area quickly, but side effects are also limited
since little or none of the drug is absorbed. In some cases, though, oral or injected drugs are
used, either instead of or in addition to topicals. Fungal infections of the toenails, for example,
may need to be treated for several months with both topical and oral antifungal drugs.
FIGURE A23 THERAPY CLASS DRUG MARKET SHARE TREND
% CHANGE IN PMPY COST
13.3%
2000 PMPY = $13.36
%
Bactroban ($38.28)
20
Elocon ($33.64)
• In Phase III of clinical trials is another bisphosphonate, Bonviva® (ibandronate). With NDA filing
expected in 2001, Bonviva® will likely have both oral and injectable forms.
Nizoral ($26.59)
10
5
0
1996
1997
1998
1999
2000
• The PMPY cost of dermatologicals grew by 13.3 percent to $13.36 in 2000. The entire increase
was due to higher costs per prescription since utilization actually declined by 1.5 percent
in 2000.
APPENDIX A
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
109
APPENDIX B
108
APPENDIX A
• In 2001, the FDA required the manufacturer of Accutane® (isotretinoin) to add a new warning
of possible CNS side effects to the label. Already carrying a warning against use in pregnancy,
Accutane® recently has been linked to depression and even suicide in some patients who were
taking it for severe resistant acne. Patients prescribed Accutane® will now sign a form to verify
they have been advised of its potential adverse effects. The patent for Accutane® expires in
August 2001.
ACTIONS
ACTIONS
• The use of generic products in this class seems to have reached a 30 percent plateau in
both 1999 and 2000. However, the average cost for generic products grew by a substantial
24.6 percent to $22.12 in 2000.
DRUG
IMPORTANCE
DRUG
IMPORTANCE
• An application for Fortéo® (recombinant parathyroid hormone) has been submitted to the FDA
for consideration in the treatment of advanced osteoporosis in postmenopausal women. Unlike
current treatments that slow the loss of bone mass, Fortéo® seems to promote growth of new
bone tissue. It will be available as an oral tablet and possibly as an inhaled form, too.
COST
FORECAST
COST
FORECAST
Lotrisone ($42.79)
25
15
Future Trends
APPENDIX B
Generic ($22.12)
30
TRENDS IN
EXPENDITURES
TRENDS IN
EXPENDITURES
35
• More convenient formulations of Fosamax® have been approved for osteoporosis after
menopause. A 70mg tablet is indicated for treatment while a 35mg tablet has an indication for
prevention. Both new strengths need to be taken only once a week. Fosamax® received approval
in September 2000 for the treatment of men who have osteoporosis.
INTRODUCTION
DERMATOLOGICALS
• In April 2000, a new lower strength of Actonel® (risedronate) received FDA approval for preventing and treating osteoporosis — either after menopause or from corticosteroid use. Previously
indicated for treating Paget’s disease, Actonel® is an oral bisphosphonate.
PREFACE
PREFACE
• 2000 PMPY expenditures for miscellaneous endocrines rose by a substantial 29.8 percent, after
growing 31.4 percent in 1999. This increase is due totally to increased utilization because average per prescription costs actually declined by 0.5 percent.
INTRODUCTION
TABLE OF
CONTENTS
TABLE OF
CONTENTS
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• The FDA granted approval as a non-prescription product to Abreva® (docosanol cream), a new
type of antiviral that keeps viral cells from entering host cells. Marketed for treatment of cold
sores and fever blisters caused by oral/facial herpes, Abreva® has no effect on viral replication
so its use should not contribute to viral resistance.
INTRODUCTION
TRENDS IN
EXPENDITURES
COST
FORECAST
ACTIONS
Future Trends
Future Trends
®
• Atrisone (dapsone topical gel) is in Phase III clinical trials for the treatment of moderate
to severe acne. It is also being investigated to relieve pain and itching from burns.
• Development has been suspended for a prescription topical antibiotic, Locilex® (pexiganan
cream). The first of a class called magainins, Locilex® was submitted to the FDA for an indication in treating diabetic foot ulcers that become infected. An FDA committee requested that
more studies be done before approval will be reconsidered.
110
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
Approximately 90 percent of people who have diabetes have Type 2. Often overweight, people with
Type 2 diabetes develop insulin resistance — meaning that the insulin they produce is not used
effectively. In some cases, insulin production also declines. As a result, glucose accumulates in
the blood. If exercise and dietary changes do not relieve symptoms, people with Type 2 diabetes
can take an oral hypoglycemic agent. Insulin may be needed in some cases.
Six classes of oral antidiabetic drugs are now available in the United States. Because each class
has a different method of action, they are frequently taken in combination with each other or with
insulin, if a single drug is not effective enough.
111
APPENDIX B
• Phase III trials have started in the United States for resiquimod, an immune response modifier,
in the treatment of recurrent genital herpes, a sexually transmitted disease (STD) caused by the
herpes simplex virus (HSV). Resiquimod is made by the same company that makes a similar
agent, Aldara® (imiquimod) for treating genital warts.
ORAL HYPOGLYCEMICS
APPENDIX A
• Clinical studies are continuing for halofuginone cream in the treatment of scleroderma. An oral
form of the drug received an orphan indication for scleroderma in early 2000. Halofuginone
inhibits specific kinds of collagen synthesis to prevent skin and internal organ damage from
excess collagen accumulation.
• The FDA accepted for review an NDA filed late in 2000 for the approval of Symlin® (pramlintide).
An injectable synthetic analogue of the hormone amylin, which helps to regulate glucose
metabolism, Symlin® can be used in both Type 1 and Type 2 diabetes. If approved, it will be
used in conjunction with insulin.
ACTIONS
APPENDIX A
• PMPY costs for antidiabetic drugs, both oral and insulins, grew 25.9 percent in 2000, after
rising 22.2 percent in 1999. Increases in the average cost per prescription accounted for
two-thirds of the 2000 increase.
DRUG
IMPORTANCE
DRUG
IMPORTANCE
• The generic for Psorcon® (diflorasone cream and ointment) was marketed in the second
quarter of 2000.
Diabetes is a risk factor for developing other chronic conditions like heart disease, hypertension,
other cardiovascular diseases and kidney failure. It is the leading cause of new cases of blindness in adults and it accounts for a significant percentage of amputations in the world.
COST
FORECAST
• Two new treatments for actinic keratoses — rough scaly spots that develop on sun-damaged
skin — were approved in 2000. Both Solaraze® (diclofenac gel) and a new cream formulation
of 5-fluorouracil that has yet not been given a brand name, received FDA approval. About
15 percent of actinic keratoses advance into skin cancers if they are not removed or treated.
A diclofenac lotion, Pennsaid®, has been approved in Europe for treating actinic keratoses
and for relieving osteoarthritis pain but it has yet to be considered by the FDA.
TRENDS IN
EXPENDITURES
• A non-steroidal ointment, Protropic® (tacrolimus) has been FDA approved for treating eczema.
Classified as an immunomodulator, Protropic® is the topical form of a drug that is used
intravenously or orally to prevent transplant rejection.
Concern is growing that the United States may be on the verge of a diabetes epidemic. According to
statistics released in January 2001 by the Centers for Disease Control and Prevention (CDC), the
number of adults in this country who have diabetes went up by about 6 percent in just one year
(between 1998 and 1999). A big cause for the increase, the CDC finds, is an even higher rise in
obesity. In 1999, almost 20 percent of U.S. adults were considered obese (commonly defined as
weighing more than 20 percent over ideal weight or having a body mass index of 28 or above) as
compared to 12 percent in 1991. If the trend continues, up to 22 million U.S. citizens could have
diabetes by the year 2025.
INTRODUCTION
• A somewhat unusual cream called Vaniqa® (eflornithine) was approved in the summer of
2000. Indicated to inhibit facial hair growth for women, Vaniqa® is undergoing further trials
to determine its usefulness for psuedofolliculitis barbae — a condition in which men develop
inflamed bumps after shaving.
People with diabetes either do not produce enough of the hormone insulin or their bodies do not
effectively utilize the insulin that is produced. Insulin regulates the amount of glucose or sugar in
the blood. The most common of the several forms of diabetes is called diabetes mellitus, which is
generally divided into two major types. The overwhelming majority of people with diabetes have
what is called Type 2. Typically appearing in adults, Type 2 diabetes is more likely to be treatable
with oral antidiabetic drugs. Type 1 diabetes used to be called juvenile diabetes because it is
most often diagnosed in children and adolescents. People with Type 1 almost always have to
inject additional insulin to control their blood sugar levels.
PREFACE
PREFACE
ANTIDIABETICS
• Olux® (clobetasol foam), a mousse form of a topical high-potency steroid, was approved for
marketing by the FDA in May 2000. Generic clobetasol cream and ointment are available.
APPENDIX B
TABLE OF
CONTENTS
TABLE OF
CONTENTS
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Sulfonylureas increase insulin release from the pancreas. The oldest class of oral antidiabetic
drugs, they can cause hypoglycemia — blood sugar levels that are too low, especially in
older patients.
• While the market shares for Precose® (acarbose) and Prandin® (repaglinide) remain at about
1 percent each, Glucophage®’s (metformin) market share continued to rise from 18.8 percent
in 1997 to 27.8 percent in 2000.
Biguanides reduce glucose production from the liver and they also increase sensitivity to insulin.
• When Rezulin® (troglitazone) was removed from the market because of its side effects in 2000,
the market shares for Avandia® (rosiglitazone) and Actos® (pioglitazone) immediately rose from
a combined 1.5 percent in 1999 to 11 percent in 2000. Both were introduced in 1999.
Meglitinides promote insulin secretion, but they are metabolized quickly making them useful
to manage hyperglycemia that can occur after meals when meals cannot be eaten on a
regular schedule.
D-phenylalanine derivatives are the newest class. They work by stimulating insulin release early
during mealtimes and by controlling surges in blood sugar levels after eating.
• Glucophage® XR (metformin extended release), a once-a-day formulation, was approved in
October 2000 for initial treatment of Type 2 diabetes. Glucovance® (metformin and glyburide)
was also given FDA approval. Glucovance® can be used for initial therapy or for patients whose
diabetes is not controlled adequately with a sulfonylurea.
FIGURE A24 THERAPY CLASS DRUG MARKET SHARE TREND
INSULINS
% CHANGE IN PMPY COST
25.9%
2000 PMPY = $18.66
%
30
Glucophage ($66.17)
Glucotrol XL ($26.17)
20
INSULINS
Glyburide/Micronized ($48.08)
15
Glipizide ($30.87)
%
10
Rezulin ($156.95)
15
5
Humulin N ($45.08)
12
1996
1997
1998
1999
2000
Humulin 70/30 ($52.63)
Humulin R ($35.05)
9
Novolin 70/30 ($66.91)
6
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
0
1996
1997
1998
1999
2000
113
APPENDIX B
112
3
APPENDIX A
• As second generation oral sulfonylurea medications become available generically, the original
brand name products are declining in use. One exception is Glucotrol® XL (glipizide sustainedrelease), which is not available generically. The use of Glucotrol® XL has maintained about an
11 percent market share since 1998.
Novolin N ($55.38)
ACTIONS
ACTIONS
0
APPENDIX A
FIGURE A25 THERAPY CLASS DRUG MARKET SHARE TREND
DRUG
IMPORTANCE
DRUG
IMPORTANCE
25
Type 1 diabetes is an autoimmune condition. People who have it produce antibodies to insulin
or to the cells that produce insulin. The result is a deficiency of natural insulin that has to be
replaced with artificially manufactured insulin. All the manufactured insulins that are currently
available are injectable products.
COST
FORECAST
COST
FORECAST
ORAL HYPOGLYCEMICS
APPENDIX B
• The first D-phenylalanine derivative was approved in early 2001. Starlix® (nateglinide), has a
mechanism of action different from other oral antidiabetic medications. With both a fast onset
and a short duration of action, it can be taken close to mealtimes — making it more convenient
for patients to use. It can be used by itself or in combination with metformin.
TRENDS IN
EXPENDITURES
TRENDS IN
EXPENDITURES
Thiazolidinediones act in ways that are different from other oral antidiabetics to raise insulin
sensitivity and to lessen glucose production.
INTRODUCTION
INTRODUCTION
Alpha-glucosidase inhibitors delay intestinal absorption of carbohydrates.
PREFACE
PREFACE
TABLE OF
CONTENTS
TABLE OF
CONTENTS
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• New indications were granted for another rapid-acting insulin, Humalog® (insulin lispro injection [rDNA origin]). Originally approved in 1996 for adults under the age of 65, Humalog® had
to be injected 15 minutes before meals. It is now indicated for children as young as 3 years old,
for people over the age of 65 and for injection immediately after meals. In addition, Humalog®
can now be used in combination with metformin.
• The FDA approved Lantus® (insulin glargine) in April 2000 for once-daily subcutaneous administration in the treatment of adult and pediatric patients with diabetes. Lantus® will be used
in patients who require basal-long-acting insulin for control of hyperglycemia.
PREFACE
COST
FORECAST
Among recent developments in cancer treatment are:
Future Trends
• An NDA is expected to be submitted this year for the FDA approval of inhaled insulin. Under
the brand name Exubera®, the product would be delivered as a dry powder using an inhalation
device similar to those used in asthma.
Trisenox® (arsenic trioxide) is an injection approved for second-line therapy in acute
promyelocytic leukemia (APL). It also has orphan designations for multiple myeloma and
for myelodysplastic syndrome.
ACTIONS
APPENDIX A
A biological drug, Pacis® (BCG, live) has been approved for treating localized cancers of the
bladder. Because it contains a live micro-organism, Bacillus Calmette-Guerin (BCG), Pacis® will
be administered in office or clinic settings where its use and disposal can be monitored. It is
intended to be given in six weekly treatments.
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
115
APPENDIX B
114
APPENDIX A
Trelstar® Depot (triptorelin pamoate) was approved in June 2000 for palliative treatment in
advanced prostate cancer.
ACTIONS
After receiving orphan status in November of 1999, Mylotarg® (gemtuzumab ozogamicin) was
approved in May 2000 for relapse of a type of leukemia in patients over the age of 60. The first
in a new class of monoclonal antibody-derived drugs called antibody-targeted chemotherapy,
Mylotarg® connects an anti-cancer drug to an antibody that is specific for antigens on leukemia
cells. Although Mylotarg® is given by injection, it can be used for outpatient treatment.
DRUG
IMPORTANCE
• The first generic products equivalent to Glucophage® should begin appearing by the end
of this year.
In May 2001, less than three months after an NDA was submitted, the FDA approved Gleevec®
(imatinib mesylate, STI 571) for the treatment of chronic myeloid leukemia (CML). Previously given
both orphan and Fast-Track designations, Gleevec® (known as Glivec® in other countries) is a signal transduction inhibitor (STI), a new class of drugs that interfere with tumor development.
Taken orally, Gleevec® selectively attacks the Philadelphia chromosome, a specific defect frequently associated with CML.
COST
FORECAST
DRUG
IMPORTANCE
With modern treatments, many cancers are not only controlled, they can be cured. For any cancer
patient, however, treatment depends on what type the cancer is and how much it has spread.
More cancer patients are becoming active partners in treatment decisions. Surgery, radiation and
drug therapy are still the standards of cancer treatment, but new techniques and products are
making these options more bearable. Some of the harsh side effects associated with drug treatment, for example, have been lessened not only by newer drugs with more specific actions, but
also by new ways to alleviate or even eliminate unwanted side effects.
TRENDS IN
EXPENDITURES
• Although the patent for Humulin® (rDNA human insulin) expired in 2000, generic equivalents
have not yet entered the market.
Years ago, the diagnosis of cancer was a virtual death sentence. By the time many cancers
showed recognizable symptoms, they had advanced too much to be treatable. In fact, according to
the American Cancer Society, less than one in five Americans who were diagnosed with cancer in
the 1930s was still living after five years. At that time and for many years after, cancer therapy
consisted mainly of palliative care and pain management. Today, preventative strategies, early
detection and enhanced treatment mean that over half of all cancer patients survive for at least
five years after being diagnosed. Many cancer survivors return to active and productive lives with
no recurrence of cancer. Even so, cancer still claims half a million lives in this country each year.
While the tendency to have some cancers is inherited, about two-thirds of all cancer deaths in the
United States are related to lifestyle — approximately one-third can be attributed to smoking cigarettes and another third involve dietary factors.
INTRODUCTION
INTRODUCTION
• A rapid-acting insulin called Novolog® (insulin aspart) was approved by the FDA in June 2000.
Because Novolog® has a fast onset and a short duration of action, it can be injected immediately before meals and still be effective. One of the major inconveniences of most insulins is
the half-hour waiting time required between injecting insulin and eating meals.
PREFACE
TRENDS IN
EXPENDITURES
ANTICANCER
• In an interesting move, the maker of Novolin® (human insulin, [rDNA origin]) has begun to
produce a private label called ReliOn®/Novolin exclusively for the Wal-Mart chain.
APPENDIX B
TABLE OF
CONTENTS
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CONTENTS
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PREFACE
TRENDS IN
EXPENDITURES
COST
FORECAST
Better screening means that many cancers are discovered sooner. A number of new laboratory
tests have recently been introduced and more are in development. For instance, beginning in
May 2000, a new blood test called DR-70® was marketed to hospitals and labs in limited areas.
DR-70® can detect up to 13 types of cancer while they are still in early stages — before symptoms become apparent. A second, similar blood test, OncoCheck® is in late phase trials. PepGen®
has already been introduced for the laboratory diagnosis of gastric cancers and peptic ulcers.
ImmunoCyt® recently became available in the United States. It is a diagnostic urine test for early
recurrent bladder cancer. A urine test for multiple myeloma has been approved in Europe and
its manufacturer plans to market it in the United States as soon as it receives FDA approval.
Already approved is a predictive genetic test named Colaris® that can assess individual risk
for hereditary colon cancer and uterine cancer genes.
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EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
Wobe-mugos, a mixture of proteolytic enzymes, was given an orphan designation in adjunct
treatment of patients with multiple myeloma. An oral drug that has been used in European countries for over 25 years, wobe-mugos will be given to alleviate the side effects of cancer drugs and
to enhance the immune system. In studies, wobe-mugos has shown effectiveness in reducing
inflammation and swelling associated with radiation, as well.
Besides orphan designations, the FDA has several other ways to make both the development and
review of new drugs quicker. Fast-Track designations are given to manufacturers seeking approval
for drugs with potential to manage previously untreatable or under treated conditions. Unlike submitting regular NDAs or BLAs, which must be complete, the manufacturer of a Fast-Track drug is
allowed to file sections of an application as soon as information is available. The FDA then reviews
each part as it is received. In Accelerated Development, an NDA/BLA can be submitted on the
basis of a single pivotal or especially significant Phase II/III study, rather than the two or more
Phase III trials required for regular submission. After NDA/BLA submission, Priority Review is
117
APPENDIX B
APPENDIX B
In the field of cancer treatment, several new drugs received orphan designations in 2000 and
early 2001.
Virulizin® received orphan designation in February 2001. In development as second-line therapy
for advanced pancreatic cancer patients who cannot tolerate or who have already tried usual drug
therapy. Virulizin® is immunotherapy — it mobilizes the body’s immune system to attack cancer cells.
APPENDIX A
Under provisions of the Orphan Drug Act, the FDA has the ability to designate orphan drugs.
Special incentives are offered to encourage the development of drugs for diseases that affect
relatively small numbers of people — generally fewer than 200,000 patients in the United States.
In exchange for incurring development costs that would ordinarily not be recouped from small
patient populations, manufacturers that choose to invest in orphan drugs are released from paying user fees, may receive research funding, are granted marketing exclusivity for seven
years and could qualify for tax credits on development costs.
The first of a new class sometimes called guanosine analogues, Tiazole® (tiazofurin), received
orphan designation early in 2001. For the treatment of accelerated-phase or blast crisis chronic
myelogenous leukemia (CML), Tiazole® and drugs like it inhibit an enzyme — inosine 5 ’monophosphate dehydrogenase (IMPDH) type II — which is concentrated in cancerous cells.
ACTIONS
ORPHANS
Thymoglobulin® (anti-thymocyte globulin, rabbit), an immunosuppressant approved for kidney
transplant patients in 1998, now has orphan status for myelodysplastic syndrome (MDS). A possible precursor to leukemia, MDS involves a defect in the production of normal blood cells.
DRUG
IMPORTANCE
DRUG
IMPORTANCE
A topical gel form of Targretin® (bexarotene 1%) was given FDA approval in July 2000. It will be
used for patients with skin lesions from early cutaneous T-cell lymphoma (CTCL) that has not
responded to other treatments. An oral form of Targretin® was approved in 1999 for CTCL.
In January 2001, an orphan indication was granted for MTC-DOX, a unique delivery method
for the cancer drug doxorubicin. Using iron and activated carbon microparticles as a carrier,
doxorubicin can be localized to specific areas of the body through the use of external magnetic
attraction. Its first indication is for primary liver cancers. Magnetic targeted carriers (MTCs), as
this type of drug has been designated, are also being investigated for other diseases as well
as for other types of cancer.
COST
FORECAST
ACTIONS
A new implanted dosage form of the drug in Lupron® (leuprolide) has been approved under the
brand name Viadur® for palliative treatment of advanced prostate cancer.
TRENDS IN
EXPENDITURES
APPENDIX A
Camptosar® (irinotecan) was given a new indication in combination with 5-FU and leucovorin for
treating metastatic colon and rectal cancers.
Genasense® (G-3139), the first of the antisense drugs to reach the U.S. market, was given Fast
Track approval status as well as an orphan designation in August 2000 for advanced malignant
melanoma. Genasense® is in clinical trials for several other cancers including prostate cancer,
multiple myeloma, chronic lymphocytic leukemia (CLL), acute myelocytic leukemia (AML), colon
cancer and lung cancer. In general, drugs of this type make cancer cells more susceptible to other
drugs and radiation. Antisense drugs are made from fragments of DNA. Called oligonucleotides,
the altered fragments stick to messenger RNA in cancer cells and prevent the production of Bcl-2
— a protein that is associated with cancer cells’ resistance to drug therapy.
INTRODUCTION
Two aromatase inhibitors that were previously approved for use after other drugs failed can now
be used as first-line treatment for advanced breast cancer in postmenopausal women. Femara®
(letrozole) and Arimidex® (anastrazole) have both received approval for this new indication.
A new dosage form of carmustine (BCNU) has been designated as an orphan drug for the treatment of glioblastoma multiforme, a type of brain cancer. Currently known as DTI-015, the drug
consists of carmustine dissolved in absolute ethanol. When it is injected directly into tumor tissue,
the tumor is literally saturated with DTI-015 yet systemic circulation of the drug is severely limited.
PREFACE
In the treatment of advanced ovarian cancer, Taxol® (paclitaxel) was approved for higher doses
given over a shorter time and less often than previous regimens. The new dosing option means
that outpatient treatment is now possible for many women who required hospitalization for
previously approved regimens. Legal maneuvers to extend patent protection for Taxol® were
overturned by a federal court. A generic was launched in November 2000.
INTRODUCTION
Nolvadex® (tamoxifen) received a new indication in reducing the risk of invasive breast cancer
for women who have had surgery or radiation for localized breast cancer.
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INTRODUCTION
Fast-Track approval is also in process for Onco TCS®, a new delivery system for vincristine. To be
used for treatment of relapses of non-Hodgkin’s lymphomas, the drug is encased in a patented
transmembrane carrier system (TCS) that not only enhances its ability to collect within the tumor
but also limits its side effects.
IMC-C225 (cetuximab), an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, has
been given Fast-Track status in treating refractory colorectal cancer. It is also in trials for the
treatment of head, neck and pancreatic cancers.
ANTICANCER
% CHANGE IN PMPY COST
20.4%
%
• An NDA was accepted for review in March 2001 for IntraDose® (cisplatin and epinephrine).
An injectable gel, IntraDose® will be used in head and neck cancers that do not respond to
current treatments or that recur after conventional treatments.
Tamoxifen ($117.34)
25
Novaldex ($110.50)
20
• An amended NDA containing information requested by the FDA will likely be filed for Foscan®
PDT (temoporfin, mTHPC) during the second quarter of 2001. A type of photodynamic therapy
in which light-sensitive drugs are activated by laser light, Foscan® has been studied for the
treatment of advanced head and neck tumors. Originally intended for palliative care of inoperable tumors, Foscan® may reduce or even eliminate tumor tissue, as well.
Megace ($189.79)
Eulexin ($292.84)
10
Intron A ($1133.42)
5
1996
1997
1998
1999
2000
• Faslodex® (fulvestrant) is an estrogen receptor downregulator, a new class of drugs being investigated for advanced breast cancers in postmenopausal women. Recent press releases from its
manufacturer indicate that NDA filing is planned for Faslodex® during the first half of 2001.
• An NDA may be submitted by the end of 2001 for rubitecan. An oral camptothecin, rubitecan is
currently in late stages of clinical testing for pancreatic cancer.
APPENDIX A
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
119
APPENDIX B
118
APPENDIX A
• The BLA for Melacine® (melanoma theraccine injection) is expected to be filed during 2001.
A vaccine to be given to patients in late stages of melanoma, Melacine® is a combination of
deactivated melanoma cells and other components that stimulate the immune system. It will
be given in a series of 20 injections over 12 weeks, followed by less frequent maintenance
injections. Another vaccine, Avicine®, is in early Phase III clinical studies for the treatment
of colorectal cancer. Phase II trials are showing good results from other vaccines including
OvaRex® Mab, for advanced recurrent ovarian cancers and BrevaRex® Mab for late stages
of breast cancer.
ACTIONS
0
DRUG
IMPORTANCE
DRUG
IMPORTANCE
Generic ($82.71)
30
15
ACTIONS
• A biologic license application (BLA) for Zevalin® (ibritumomab tiuxetan) was accepted for
priority review in January 2001. A monoclonal antibody attached to a radioisotope, it will be
used along with Rituxan® (rituxumab) — a second monoclonal antibody drug. Zevalin® is
being considered for the treatment of several forms of non-Hodgkin’s lymphoma.
2000 PMPY = $8.54
35
APPENDIX B
• An NDA was filed in mid-December 2000 for abarelix depot-M, an inhibitor of gonadotropin
releasing hormone (GnRH). Accepted for priority review in January 2001, the initial NDA is for
treating prostate cancer. Clinical trials for endometriosis and other indications are continuing.
COST
FORECAST
COST
FORECAST
FIGURE A26 THERAPY CLASS DRUG MARKET SHARE TREND
• The BLA for Bexxar® (tositumomab, iodine I 131 tositumomab) was filed in September 2000.
Bexxar® is a monoclonal antibody with radioactive iodine 131 attached to it. The antibody seeks
out and fastens to a protein located only on the surface of cancerous B-cells found in many
forms of non-Hodgkin’s lymphoma. The radioactive element then destroys the cancer cells.
TRENDS IN
EXPENDITURES
Phase III trials continue for Protegrin IB-367 Rinse, which is on Fast-Track for FDA approval.
The most advanced commercial application of adapted natural antibiotic peptides, the drug is
being developed to relieve pain and prevent infection of mouth sores that result from many
chemotherapy and radiation regimens. Other protegrins are in trials for respiratory conditions.
• In December, the FDA’s Oncologic Drugs Advisory Committee recommended approval for
Campath® (alemtuzumab) in the treatment of chronic lymphocytic leukemia (CLL). Campath® is
a monoclonal antibody that was given orphan status as well as accelerated review in 2000. It is
in further testing for other cancers, for transplant rejection and for multiple sclerosis.
INTRODUCTION
TRENDS IN
EXPENDITURES
An inhibitor of the enzyme, thymidylate synthase, Thymitaq® (nolatrexed dihydrochloride), has
entered Phase III clinical investigation for several types of cancer. It has been most researched for
liver cancers that cannot be removed surgically. It was given Fast-Track status in April 2000.
Future Trends
PREFACE
PREFACE
granted for drugs that offer significant improvements in prevention, diagnosis or treatment of lifethreatening or severely debilitating conditions. Priority reviews are completed within six months.
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PREFACE
INTRODUCTION
TRENDS IN
EXPENDITURES
COST
FORECAST
• Alimta® (pemetrexed disodium — also called LY 231, 524 or MTA) is an antifolate-type anticancer drug that is different from earlier folate inhibitors. It disrupts three or more enzymes
involved in folate synthesis — an essential part of cancer cell replication. Alimta® is in Phase
III and earlier trials for treatment of several solid tumor forms of cancer.
• IMG 862 is an investigational angiogenesis inhibitor, a class of drugs that received a lot of
attention in the popular press a couple of years ago. Although not as revolutionary as first
expected, the angiogenesis inhibitors do hold promise. As a class, they seem to stimulate the
immune system as well as inhibiting the growth of new blood vessels to tumor tissue. IMG 862,
given as nose drops, is in various phases of clinical trials for a number of cancer types including Kaposi’s sarcoma and prostate cancer.
• Following a Not Approvable letter that was issued in September 2000, new information will be
submitted to amend the original NDA for Aptosyn® (exisulind), a selective apoptotic antineoplastic drug (SAAND). Aptosyn® was originally submitted for approval to treat familial adenomatous
polyps, a precursor to colon cancer. In combination with Taxotere® (docitaxel), Aptosyn® is being
tested for patients with non-small cell lung cancer that has not responded to previous drug
treatment. It is in earlier stages of research for several other types of cancer, too. SAANDs promote apoptosis (also called programmed cell death) of cancer cells but not normal cells.
• An application for Ceplene® (histamine dihydrochloride) — formerly called Maxamine® — was
deemed Not Approvable by the FDA in December 2000. Even though it had been given orphan status
early in 2000, Ceplene®’s full approval was denied in part because trial designs may not have been
randomized adequately. An immunotherapy, it was studied in combination with interferon to protect
immune cells for patients with metastatic malignant melanoma. Additional testing will be done for
the melanoma indication while Phase III and Phase II trials continue for other cancers and for
hepatitis C.
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APPENDIX B
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
• Promycin® (porfiromycin) has also shown poor results in Phase III trials for inoperable head
and neck cancers. Further studies that were planned for its use have been delayed and may
eventually be cancelled.
APPENDIX A
120
• Whether further trials will be conducted for matrix metalloproteinase inhibitors (MMPIs) is in
doubt. Phase III trials of the lead compound, marimastat, showed no appreciable benefit over
placebo in treating small cell lung cancer, glioblastoma or pancreatic cancers. Phase III clinical
trials for another MMPI, prinomastat, were terminated in the summer of 2000 after it, too, had
disappointing results in treating advanced cases of prostate and non-small cell lung cancer.
ACTIONS
• Bacillus Calmette-Guerin (BCG) is being tested in combination with BEC2 (mitumomab). BEC2
is a monoclonal antibody that acts like GD3, an antigen on the surface of some kinds of cancer
cells. BCG stimulates the immune system to attack BEC2 and, as a result, GD3 is also
destroyed. Phase III trials are under way to determine the combination’s effectiveness and safety in delaying or preventing recurrence of small cell lung cancers. It is also in trials for other
lung cancers and for malignant melanoma.
• NDAs for UFT® (tegafur/uracil) and for Orzel® (UFT® and leucovorin) were withdrawn by the
manufacturer early in 2000. Plans are to resubmit both drugs in the oral treatment of colorectal
cancers after the FDA has reviewed additional information submitted by the manufacturer.
DRUG
IMPORTANCE
• Metvix®, a derivative of 5-aminolevulinic acid (ALA), is a photoactivated cream that is applied
to actinic keratoses, allowed to accumulate for about three hours then activated by a specific
wavelength of red light. Only treated tissue is destroyed, very little skin around the treated area
is affected and scarring is minimal. Phase II trials have been completed in the United States
and in Australia.
• Additional trials are being conducted for oxiplatin after an FDA committee determined that it
was not effective enough to be approved as first-line therapy for metastatic colon cancer. An
NDA will be submitted for second-line therapy but not for at least a year.
COST
FORECAST
DRUG
IMPORTANCE
• Irofulven (also called MGI 114, hydroxymethylacylfulvene or HMAF) is the first drug in the
acylfulvene class. Currently beginning approximately 18 months of Phase III trials for patients
with advanced pancreatic cancer, it is also in earlier phase trials for other cancers that appear
as solid tumors.
• A new selective estrogen receptor modulator (SERM), arzoxifene (LY-353, 381) is in Phase III
testing for advanced breast cancer and in earlier phases for endometrial cancer.
TRENDS IN
EXPENDITURES
ACTIONS
• Phase III trials are being conducted for the use of eflornithine (DFMO) for treating cancers of the
bladder surface and non-melanoma skin cancers. It is also in the early stages of testing for
other cancers. Eflornithine permanently blocks an enzyme critical to cancer cell replication.
• Phase II trials continue and Phase III studies have begun for Allovectin-7® (HLA-B7/Beta2M DNA
Lipid DMRIE/DOPE complex) in the treatment of malignant melanoma and head/neck cancers.
The first in a new class that links human antibodies to lipids, Allovectin-7® has already been
given orphan approval for treating metastatic melanoma.
INTRODUCTION
APPENDIX A
• Another vaccine-type treatment called Oncophage® has entered Phase III trials in treating renal
cell cancer. A heat shock protein-peptide complex, Oncophage® is derived from tumor cells that
are surgically removed from individual patients, specially treated under laboratory conditions,
then re-introduced into the patient to promote a strong immune response against the remaining
cancer cells. Oncophage® is also under investigation for multiple other cancers.
PREFACE
APPENDIX B
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• An amended NDA for Atragen® (tretinoin liposome for injection) to treat acute promyelocytic
leukemia was denied by the FDA in January 2001 because the agency saw no need for an
injectable form of a drug which is available orally. The manufacturer will submit applications
for approval in Europe as well as in the United States for other types of cancer.
• Zometa® (zoledronic acid) is a bisphosphonate being investigated for treating hypercalcemia
of malignancy (HCM). A complication of advanced cancers, HCM occurs in approximately onetenth of cancer patients. Zometa® received priority review after being granted orphan status
in August 2000. In September, it was deemed Approvable pending additional information on
its use in metastatic bone complications.
• Palonsetron is a 5HT3 antagonist similar to Kytril® (granisetron) and Zofran® (ondansetron).
It is currently in late Phase III trials. An NDA for palonsetron to be used in controlling
chemotherapy-induced nausea and vomiting could be filed in early 2002.
APPENDIX B
APPENDIX A
ACTIONS
DRUG
IMPORTANCE
COST
FORECAST
TRENDS IN
EXPENDITURES
INTRODUCTION
Besides developing drugs involved in the direct treatment of cancer, other drugs are being studied
that target side effects of the disease or its treatment. For example:
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TABLE OF
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B
a ppendix
PREFACE
TRENDS IN
EXPENDITURES
COST
FORECAST
DRUG
IMPORTANCE
ACTIONS
APPENDIX A
APPENDIX B
123
INTRODUCTION
Dr ug Utilization and
Cost by Sex and Age
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D R U G U T I L I Z AT I O N A N D C O S T B Y S E X A N D A G E
This portion of the Drug Trend Report examines variations in drug utilization and cost as related to the
sex and age of Express Scripts’ members. The first section of Appendix B discusses the most frequently
used therapy classes, the second section examines overall utilization and cost, and the third section
details drug utilization by therapy class for male and female members within a given age group.
TRENDS IN
EXPENDITURES
.TABLE B1
MOST FREQUENTLY USED THERAPY CLASSES BY SEX AND AGE
DRUG
IMPORTANCE
1
2
3
4
5
6
7
8
9
10
Therapy Class
Estrogens
Antidepressants
Oral Contraceptives
Antihypertensives
Narcotic Analgesics
Antirheumatics/NSAIDs
Cough/Cold
Gastrointestinal
Thyroid
Antihistamines
Percent of
Prescriptions
Rank
8.0
6.9
5.5
4.7
4.6
4.0
3.8
3.7
3.5
3.2
1
2
3
4
5
6
7
8
9
10
Therapy Class
Antihypertensives
Antihyperlipidemics
Antidiabetics
Narcotic Analgesics
Gastrointestinal
Antidepressants
Antirheumatics/NSAIDS
Antiasthmatics
Beta Blockers
Cough/Cold
9.4
6.8
5.3
5.1
4.6
4.5
4.1
4.0
4.0
3.8
Table B1 shows the 10 most frequently used therapy classes for females and males with the
percentages of prescriptions filled in each class, respectively.
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
1 Lowenthal K, et al. Gender and depression in Anglo-Jewry. Psychological Medicine 1995;25(5):1051-1064.
2 National Heart, Lung, and Blood Institute (NHLBI). Cardiovasuclar Information for Patients and the General Public.
www.nhlbi.nih.gov/health/public/heart/index.htm Accessed March, 2001.
3 Centers for Disease Control and Prevention. National Diabetes Fact Sheet: National estimates and general information on
diabetes in the United States. Revised edition. Atlanta, GA: U.S. Department of Health and Human Services, Centers for
Disease Control and Prevention, 1998. www.cdc.gov/diabetes/pubs/facts98.htm#prev
4 de Marco R, Locatelli F, Sunyer J, Burney P. Differences in incidence of reported asthma related to age in men and women.
A retrospective analysis of the data of the European Respiratory Health Survey. American Journal of Respiratory Critical
Care Medicine. 2000;162(1):68-74.
5 Mosca L, Manson JE, Sutherland SE, Langer RD, Manilo T, Barrett-Conner E. Cardiovascular disease in women: a statement
for healthcare professionals from the American Heart Association. Writing Group. Circulation 1997;96:2468-2482.
125
APPENDIX B
124
The order in which the top 10 therapy classes were ranked did not change considerably from
the previous year for either sex. Antihistamines replaced penicillins on the list for females —
as the 10th most frequently used therapy class. For males, beta blockers and anti-rheumatics
replaced penicillins and calcium blockers. While penicillins and beta blockers were ranked ninth
on the lists for 1999 and 2000, respectively, the anti-rheumatics class made its first appearance
on the 2000 top 10 list in the seventh position.
APPENDIX A
APPENDIX A
Accounting for 8 percent of all prescriptions filled by females, estrogens were the most frequently
used therapy class among women for the second consecutive year. Although a small number of
men use estrogen or oral contraceptive therapy for certain types of cancer, estrogens are primarily
used by women to replace post-menopausal hormone loss and to decrease the risk of osteoporosis.
In addition to the antihypertensives, four other commonly used therapy classes made the list
for both males and females but had slightly different rankings. These therapy classes are
anti-rheumatics, gastrointestinals, cough/cold and narcotic analgesics.
ACTIONS
APPENDIX B
Percent of
Prescriptions
Antiasthmatics and beta blockers were both among the most frequently used therapy classes for
males, yet neither made it into the top 10 list for females. The prevalence of asthma is slightly
higher for males than it is for females during childhood, but the trend is reversed in adults.4 Beta
blockers continue to gain acceptance in the treatment of mild to moderate heart failure. However,
evidence suggests that women are less likely to receive adequate treatment for heart failure due
to misconceptions about their lower risks for developing heart disease.5
DRUG
IMPORTANCE
ACTIONS
Rank
Males
As in 1999, antihypertensives, antihyperlipidemics and antidiabetics were the top three therapy
classes used by males in 2000. While more men develop high blood pressure and high cholesterol
before the age of 50, the incidence of both conditons increases in women after the fifth and sixth
decade of life following the onset of menopause.2 Diabetes appears to be equally prevalent among
men and women, especially after the age of 45.3 However, only antihypertensives ranked among
the 10 most common therapy classes used by females.
COST
FORECAST
COST
FORECAST
Females
Oral contraceptives were third on the list of frequently used therapy classes for females. Other
therapy classes that ranked among the top 10 for females but did not appear on the list for males
include thyroid drugs and antihistamines.
TRENDS IN
EXPENDITURES
Data used in Appendix B were taken from a database constructed for research purposes by Express
Scripts. From the entire set of members who provided data for earlier sections of the Drug Trend
Report, 2,265,669 members were selected randomly. All outpatient prescription pharmacy claims
processed for these members during calendar year 2000 were obtained. From that research data
pool, a random sample of one million claims was used. Claims for prescriptions processed through
the mail pharmacy service were converted to 30-day network equivalents. A final total of 1,130,966
network equivalent claims were analyzed. Each claim included the member’s sex and age, the drug
name, the prescription fill date and the days’ supply that was dispensed. Drug utilization and cost
were then compared between males and females, and among members of various age groups.
INTRODUCTION
INTRODUCTION
METHODS
Antidepressants were the second most common therapy class used by females. This class was
ranked eighth among males during 1999, but rose to sixth place in 2000. The fact that women
are twice as likely as men to be diagnosed with depression may be explained by social and environmental influences as well as by sex differences. Some studies suggest that men are less likely
to recognize or acknowledge that they are suffering from depression and, as a result, are less
likely to seek treatment.1
PREFACE
PREFACE
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PREFACE
TABLE B2
TABLE B3
MOST FREQUENTLY USED THERAPY CLASSES BY AGE
MOST FREQUENTLY USED THERAPY CLASSES BY SEX AND AGE.
Therapy Class
1
2
3
4
5
Penicillins
Antiasthmatics
Cough/Cold
Antihistamines
Cephalosporins
22.5
9.1
8.7
8.0
7.6
1
2
3
4
5
Dermatologicals
Penicillins
Antiasthmatics
Stimulants/Anti-obesity
Antihistamines
1
2
3
4
5
10 to 19 Years
30 to 39 Years
40 to 49 Years
APPENDIX A
80 Years and Above
Rank Therapy Class
Birth to 9 Years
11.5
8.0
7.2
6.9
6.7
1
2
3
4
5
Penicillins
Cough/Cold
Cephalosporins
Antiasthmatics
Antihistamines
23.9
9.0
8.0
7.5
7.5
1
2
3
4
5
Penicillins
Antiasthmatics
Antihistamines
Cough/Cold
Cephalosporins
21.3
10.4
8.5
8.5
7.3
10 to 19 Years
Oral Contraceptives
Narcotic Analgesics
Antidepressants
Cough/Cold
Dermatologicals
18.6
7.1
6.2
5.9
5.4
1
2
3
4
5
Dermatologicals
Oral Contraceptives
Penicillins
Cough/Cold
Antihistamines
10.8
10.1
8.2
6.7
6.2
1
2
3
4
5
Dermatologicals
Stimulants/Anti-obesity
Antiasthmatics
Penicillins
Antihistamines
12.3
11.0
8.4
7.8
7.3
20 to 29 Years
1
2
3
4
5
Oral Contraceptives
Antidepressants
Narcotic Analgesics
Cough/Cold
Anti-rheumatics
8.9
8.4
7.8
5.6
4.2
1
2
3
4
5
Oral Contraceptives
Antidepressants
Narcotic Analgesics
Cough/Cold
Dermatologicals
25.0
6.2
5.9
5.2
4.9
1
2
3
4
5
Narcotic Analgesics
Cough/Cold
Dermatologicals
Antidepressants
Penicillins
10.5
7.9
6.8
6.0
5.8
30 to 39 Years
1
2
3
4
5
Antidepressants
Antihypertensives
Narcotic Analgesics
Estrogens
Gastrointestinals
8.5
6.5
6.3
5.3
4.7
1
2
3
4
5
Oral Contraceptives
Antidepressants
Narcotic Analgesics
Cough/Cold
Anti-rheumatics
13.2
9.1
6.9
5.3
3.8
1
2
3
4
5
Narcotic Analgesics
Antidepressants
Cough/Cold
Gastrointestinals
Anihypertensives
9.5
6.7
6.3
5.8
5.7
40 to 49 Years
1
2
3
4
5
Estrogens
Antihypertensives
Antihyperlipidemics
Antidepressants
Antidiabetics
10.1
9.1
6.6
5.8
5.1
1
2
3
4
5
Antidepressants
Estrogens
Narcotic Analgesics
Antihypertensives
Anti-rheumatics
9.7
8.3
5.7
4.5
4.5
1
2
3
4
5
Antihypertensives
Narcotic Analgesics
Antihyperlipidemics
Antidepressants
Gastrointestinals
10.0
7.3
7.2
6.2
5.6
50 to 59 Years
1
2
3
4
5
Antihypertensives
Antihyperlipidemics
Estrogens
Antidiabetics
Diuretics
10.5
8.4
6.3
6.1
5.0
1
2
3
4
5
Estrogens
Antidepressants
Antihypertensives
Anti-rheumatics
Gastrointestinals
16.1
6.7
6.6
4.4
4.3
1
2
3
4
5
Antihypertensives
Antihyperlipidemics
Antidiabetics
Beta Blockers
Calcium Blockers
13.0
10.5
7.5
5.4
5.2
60 to 69 Years
1
2
3
4
5
Antihypertensives
Antihyperlipidemics
Diuretics
Beta Blockers
Calcium Blockers
10.2
7.5
6.1
5.5
5.5
1
2
3
4
5
Estrogens
Antihypertensives
Antihyperlipidemics
Diuretics
Antidepressants
11.3
7.9
6.5
5.3
4.6
1
2
3
4
5
Antihypertensives
Antihyperlipidemics
Antidiabetics
Beta Blockers
Calcium Blockers
13.8
10.6
7.9
5.9
5.7
70 to 79 Years
1
2
3
4
5
Antihypertensives
Diuretics
Calcium Blockers
Gastrointestinals
Beta Blockers
1
2
3
4
5
Antihypertensives
Diuretics
Antihyperlipidemics
Calcium Blockers
Estrogens
8.6
6.7
6.5
5.2
5.2
1
2
3
4
5
Antihypertensives
Antihyperlipidemics
Antidiabetics
Beta Blockers
Calcium Blockers
11.9
8.5
6.5
6.2
5.7
80 Years and
Above
1
2
3
4
5
Antihypertensives
Diuretics
Calcium Blockers
Gastrointestinals
Thyroid
8.6
8.3
6.3
5.0
4.6
1
2
3
4
5
Antihypertensives
Diuretics
Calcium Blockers
Beta Blockers
Antihyperlipidemics
11.3
7.3
5.5
5.0
4.9
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
9.7
7.8
6.0
4.7
4.7
Rank Therapy Class
127
APPENDIX B
126
Age Group
APPENDIX A
APPENDIX B
70 to 79 Years
Males
Percent of
Prescriptions
ACTIONS
ACTIONS
60 to 69 Years
Percent of
Prescriptions
DRUG
IMPORTANCE
DRUG
IMPORTANCE
50 to 59 Years
Females
COST
FORECAST
COST
FORECAST
TRENDS IN
EXPENDITURES
20 to 29 Years
Percent of Prescriptions
TRENDS IN
EXPENDITURES
Rank
Birth to 9 Years
INTRODUCTION
Age Group
PREFACE
INTRODUCTION
TABLE OF
CONTENTS
TABLE OF
CONTENTS
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TABLE OF
CONTENTS
22501_appB
Starting in the fifth decade, antihypertensive medications joined the list of the top five most
frequently used therapy classes. These drugs then occupied the first or second position for the
remainder of the life span. Drugs in other therapy classes, such as diuretics, beta blockers and
calcium blockers, that are used to treat high blood pressure became widely used among members
60 years of age and above. Antihyperlipidemics were also commonly used by older members.
128
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
Since these analyses are based on a random sample of claims, the underlying sex and age distribution of sample members is unavailable. Therefore, these analyses are for descriptive purposes
only and do not provide the reason(s) for relatively high or low utilization by a sex/age category.
That is, particularly high or low utilization within a sex/age category could be due to the relative
number of members in that category, to the relative usage of drugs per category member or to a
combination of both factors.
8 The Alan Guttmacher Institute. Facts in Brief: Contraceptive Use. 2000. www.agi-usa.org/pubs/fb_contr_use.html
129
APPENDIX B
6 National Heart, Lung, and Blood Institute (NHLBI) Data Fact Sheet. Asthma Statistics. January 1999.
Publication No.: 55-798. www.nhlbi.nih.gov/health/prof/lung/asthma/asthstat.htm Accessed March, 2001.
7 The Alan Guttmacher Institute. Facts in Brief: Contraceptive Use. 2000. www.agi-usa.org/pubs/fb_contr_use.html
Accessed March, 2001.
OVERALL UTILIZATION AND COST BY SEX AND AGE
APPENDIX A
Table B3 further categorizes drug use by sex and age. The most frequently used therapy classes
differed very little between males and females from birth to 9 years of age. Drugs in the stimulant/anti-obesity class represented 11 percent of the prescriptions filled for males in the 10-19
age group. The drugs were not, however, among the top five therapy classes for females in any
age group or for males of other ages.
Anti-rheumatics represented the number five therapy class for females between the ages of 30-49,
then climbed to number four in the next decade. This therapy class was not in any of the listings
for men, however. Antihyperlipidemics made the top five list for males beginning in their 40s but
did not appear on the list for females until the 60-69 year age group. Antidiabetics were among
the most commonly used therapy classes only for men aged 50-79 years.
ACTIONS
Although gastrointestinals entered the top five list for the 40-49 year old age group, they
disappeared from the list for the next three age groups and then reappeared as the fourth most
commonly used therapy class by members 80 years of age and older.
INTRODUCTION
TRENDS IN
EXPENDITURES
COST
FORECAST
Antihypertensives made the top five most frequently used therapy class list for males beginning
in their 30s and for females in their 40s. While they remained as the number one class for males
in all age groups above the age of 40, antihypertensives rose from fourth place among females in
the 40-49 year age group to third place for females in the next two age groups. Antihypertensives
finally reached the top of the list for females 70 years of age and older. Calcium blockers, diuretics
and beta blockers — also used in the treatment of high blood pressure as well as for various
types of heart disease — began to appear on the top 10 list for males in the 50-59 year age
group and for females a decade older.
DRUG
IMPORTANCE
DRUG
IMPORTANCE
The overwhelming majority of women in their childbearing years fall into the 20-29 year and the
30-39 year age brackets — explaining why oral contraceptives were once again the most frequently
used therapy class for members in their 20s and 30s. Statistics indicate that oral contraceptives
are the most widely used form of birth control by women in their 20s.7 Rising from fifth place in
1999, antidepressants ranked third among members 20-29 years of age and remained among the
top five therapy classes for the next three decades.
The estrogens class began to be used frequently by females in the 40-49 year age bracket,
marking the transition into menopause. It then rose to the most commonly prescribed therapy
class among female members in their 50s and 60s. Estrogens disappeared from the top five list,
though, for female members 70 years of age and older.
COST
FORECAST
ACTIONS
Anti-infectives, antiasthmatics and antihistamines were also on the top five list for 10-19 year
olds. The most commonly used therapy class for this age group was dermatologicals — drugs
used to treat chronic skin conditions such as acne and ezcema as well as acute skin infections and
rashes. Rounding out the top five therapy classes for teens and preteens were the stimulant/antiobesity drugs. This class includes drugs used to treat attention-deficit/hyperactivity disorder
(ADHD), a condition more commonly diagnosed in males than in females.
Antidepressants were the second most frequently used therapy class among females aged 20-29
years and the fourth among males in the same age group. The use of antidepressants increased
in frequency for members in their 30s — ranking in second place for both sexes. They continued
to be among the top five for females up to the age of 69 but dropped out of the top five for males
after age 49.
TRENDS IN
EXPENDITURES
APPENDIX A
The most frequently used therapy classes for children from birth through 9 years of age included
anti-infectives, antiasthmatics, cough/cold and antihistamines. The prevalence of asthma in children younger than 4 years of age has increased has dramatically over the last decade. According
to one source, asthma is more prevalent only in individuals between 5 and 14 years of age.6 Other
allergic disorders, such as hay fever, are very common among infants and children as well.
Narcotic analgesics, used to treat both chronic and acute pain of various origins, ranked among
the top five therapy classes in the 20-29 year age group for both males and females. This therapy
class remained on the list in the next two age groups for both sexes, although the rankings varied.
Interestingly, narcotic analgesics dropped out of the top five for both males and females after the
age of 49 years.
INTRODUCTION
APPENDIX B
For the youngest age group, the top five therapy classes were primarily made up of drugs used to
treat acute conditions. With increasing age, members were more and more likely to use drugs for
the treatment of chronic conditions.
Oral contraceptives accounted for 10.1 percent of the prescriptions used by females in the 10-19
year age group. According to one source, 44 percent of teenage women who use any form of birth
control choose oral contraceptives.8 Not surprisingly, the most frequently used therapy class for
females in their 20s was also the oral contraceptives — accounting for one-quarter of all
prescriptions used by that group.
PREFACE
PREFACE
Table B2 illustrates prescription drugs used by Express Scripts members in nine different age
categories. For each of the age groups, the five most frequently used therapy classes are listed
along with the percentage of prescriptions filled for that class.
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TABLE OF
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TABLE OF
CONTENTS
22501_appB
TABLE B4
OVERALL DRUG UTILIZATION BY SEX AND AGE
% of Prescriptions 9
INTRODUCTION
Total
Females
Males
Total
Birth-9 years
10-19 years
20-29 years
30-39 years
40-49 years
50-59 years
60-69 years
70-79 years
80+ years
24,805
33,144
60,299
101,182
156,595
177,521
85,285
35,007
14,128
30,875
30,971
21,243
49,363
88,509
109,097
69,827
32,144
10,971
55,680
64,115
81,542
150,545
245,104
286,618
155,112
67,151
25,099
2.2
2.9
5.3
8.9
13.8
15.7
7.5
3.1
1.2
2.7
2.7
1.9
4.4
7.8
9.6
6.2
2.8
1.0
4.9
5.7
7.2
13.3
21.7
25.3
13.7
5.9
2.2
Total
687,966
443,000
1,130,966
60.8
39.2
100.0
Table B4 shows the number and percentage of prescriptions for all therapy classes combined that
were attributable to females, to males and to all members combined in each age group.
The 95-percent confidence intervals were calculated for each of the sample percentages shown
in Table B4. Confidence intervals estimate how closely values based on a sample represent the
population values (in this case, the values that would have resulted if the entire Express Scripts
Drug Trend database had been used in these analyses). The 95-percent confidence interval calculations indicate that each of the sample percentages is accurate within +/-0.1 percent. For example,
Table B4 states that females aged 0-9 years accounted for 2.2 percent of sample prescriptions.
The confidence interval calculation indicates a 95 percent probability that the percentage of
prescriptions attributable to females between the ages of birth-9 years in the entire Express
Scripts database lies between 2.1 percent and 2.3 percent.
TABLE B5
PERCENT OF TOTAL AWP, MEAN AWP PER PRESCRIPTION AND PERCENT
CHANGE IN MEAN AWP PER PRESCRIPTION BY SEX AND AGE GROUPS
FIGURE B1
TRENDS IN
EXPENDITURES
TRENDS IN
EXPENDITURES
Males
INTRODUCTION
Females
PREFACE
PREFACE
# of Prescriptions
Age Group
Overall, more prescriptions were filled for females than for males during 2000. However, little difference was evident in the percentage of prescriptions attributed to each sex in the two youngest
and the two oldest age groups. Although females filled 60.8 percent of prescriptions during 2000,
they made up only 50 percent of the members in the original research database. Taken together,
these two findings indicate that females filled more prescriptions per member than males.
PERCENT OF PRESCRIPTIONS FILLED BY MEMBERS OF EACH SEX AND AGE CATEGORY
COST
FORECAST
% of Total AWP
Females
15.7
Males
13.8
9.6
8.9
10
7.8
5
2.2
2.7
2.9 2.7
7.5
6.2
5.3
4.4
3.1 2.8
1.9
1.2 1.0
Females Males
% Change in
Mean AWP from
1999 to 2000
Mean AWP
per Prescription
Males
Total
Birth-9 years
10-19 years
20-29 years
30-39 years
40-49 years
50-59 years
60-69 years
70-79 years
80+ years
1.3
2.7
4.3
8.4
14.0
15.2
7.3
3.1
1.1
1.8
3.0
1.9
5.0
9.3
11.0
6.8
3.0
0.9
Total Females
3.1
5.6
6.2
13.4
23.3
26.2
14.1
6.1
2.1
$31.94
$47.56
$42.26
$49.22
$52.81
$50.59
$50.90
$51.86
$47.63
$34.27
$56.88
$52.45
$59.89
$62.27
$59.88
$57.77
$55.34
$50.07
Males
$33.23
$52.06
$44.92
$52.72
$56.23
$54.13
$53.99
$53.52
$48.70
Total Females
20.3
13.7
11.3
12.1
13.4
13.3
9.8
5.0
6.2
15.4
12.8
12.2
13.7
13.5
10.5
7.5
4.6
2.2
17.6
13.4
11.9
13.0
13.6
12.4
8.9
5.0
4.9
Totals
57.3
42.7
100.0
$49.39
$57.10
$52.41
12.2
11.3
12.0
DRUG
IMPORTANCE
% of Prescriptions
15
DRUG
IMPORTANCE
Age Group
10
COST
FORECAST
%
20
0
ACTIONS
20-29
years
30-39
years
40-49
years
50-59
years
60-69
years
70-79
years
80+
years
9 Due to rounding error, the sum of the percentage of prescriptions used by males and females within an age group may not
exactly equal the total percentage of prescriptions filled by that age group. Likewise, also due to rounding error, the sum of
the percentages of prescriptions filled by females, or by males, of each age group may not exactly equal the total percentage of prescriptions filled by that sex.
130
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
10 Due to rounding error, the sum of the percentage of AWP attributed to males and females within an age group may not
exactly equal the total percentage of AWP attributed to that age group. Likewise, also due to rounding error, the sum of
the percentages of AWP attributed to females, or to males, of each age group may not exactly equal the total percentage
of AWP attributed to that sex.
131
APPENDIX B
APPENDIX B
APPENDIX A
APPENDIX A
10-19
years
ACTIONS
0-9
years
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Page 132
PREFACE
INTRODUCTION
TRENDS IN
EXPENDITURES
MEAN AWP PERCENT CHANGE FROM 1999 TO 2000 BY SEX AND AGE
DRUG
IMPORTANCE
AWP % Change
15.4
13.7
15
13.7
12.8
11.3
12.2
13.4 13.5
13.3
12.1
10.5
9.8
10
7.5
5.0 4.6
5
ACTIONS
ACTIONS
Males
DRUG
IMPORTANCE
Females
20.3
Conversely, cost increases were smaller in the top six classes used by adults 80 years and above
(6.4 percent for antihypertensives, 4.5 percent for calcium blockers, 9.2 percent for gastrointestinals, 7.0 percent for beta blockers, 5.4 percent for antihyperlipidemics and 6.3 percent for diuretics). These classes made up 37.4 percent of all 2000 prescriptions for members aged 80 years and
over, and, when weighted by number of 2000 prescriptions, increased an average of 6.4 percent.
As the above discussion illustrates, differences in drug trend across particular age or gender
groupings are reflective of changes in drug classes used by that subgroup. Consequently, policy
statements on drug trend should focus more on individual therapy classes as they can often drive
the variation in drug trend across subgroups.
25
20
Part of the reason for this pattern of results concerns the relative increase in cost per prescription
from 1999 to 2000 for the drug classes used by children and older adults. For example, other Drug
Trend Report data indicate that the mean AWP per prescription increased 14.8 percent for penicillins, 12 percent for asthma medications, 17 percent for cough/cold drugs, 6.9 percent for antihistamines, 2.2 percent for cephalosporins and 15.1 percent for dermatologicals. These top six
classes used by children aged birth to 9 accounted for 68.3 percent of prescriptions for that age
group during 2000. When weighted by percent of 2000 prescriptions, these classes showed an
average 1999-2000 increase of 11.5 percent.
COST
FORECAST
FIGURE B2
However, the manner in which the overall cost per prescription increase was manifested in terms
of age changed dramatically over 1999-2000 compared to 1998-1999. Across 1998 and 1999,
the most dramatic increases occurred for adults aged 70 years and above. Between 1999 and
2000, however, the largest increases in cost per prescription were shown for children between
the ages of birth and 9 years, while adults 70 years and older showed the smallest increase in
per prescription costs.
TRENDS IN
EXPENDITURES
The 95-percent confidence interval calculations indicate a 95 percent probability that each of the
sample percentages listed under the heading “% of Total AWP” in Table B5 were within +/-0.1
percentage points of the corresponding percentage values which would have resulted if the entire
Express Scripts Drug Trend database had been analyzed. Likewise, 95-percent confidence interval
calculations indicate that for each of the mean AWP values calculated from the sample (Table
B5), there is a 95 percent probability that the corresponding mean AWP value in the entire ESI
Drug Trend database lies within +/-$1.60 of the sample mean.
Between 1998 and 1999, the mean AWP per prescription overall rose by 9.6 percent. The increase
was larger between 1999 and 2000, 12.1 percent. Like the 1998-1999 period, between 1999 and
2000, increases in cost per prescriptions were slightly larger for females than for males.
INTRODUCTION
Average Wholesale Price (AWP) was used to reflect ingredient cost in these analyses — ensuring
comparability across time and for all clients. Table B5 presents the percent of AWP costs accounted
for by each sex/age group combination and the mean AWP per prescription in the year 2000. Table
B5 and Figure B2 show the percent change in mean AWP per prescription from 1999 to 2000 as a
function of age and sex. The percentage of total pharmacy costs (percent of total AWP) for each of
the sex/age group categories in 2000 was similar to that shown in 1999. Once again, the majority
of costs were attributable to members aged 20 through 59 years. Females accounted for 60.8 percent of all prescriptions filled by Express Scripts members but only 57.3 percent of costs, indicating
that the mean cost per prescription is less for females than males. The mean AWP per prescription
was $49.39 for females and $57.10 for males. As in 1999, children under 10 years of age had the
lowest average cost per prescription of all the age categories, paying a mean of $33.23. Whereas
members in their 70s comprised the age group with the highest mean cost per prescription in
1999, the title in 2000 was held by members aged 40-49 years — who paid $56.23 per prescription
on average.
PREFACE
COST
FORECAST
TABLE OF
CONTENTS
TABLE OF
CONTENTS
22501_appB
6.2
2.2
0
10-19
years
20-29
years
30-39
years
40-49
years
50-59
years
60-69
years
70-79
years
80+
years
132
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
133
APPENDIX B
APPENDIX B
APPENDIX A
APPENDIX A
0-9
years
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Page 134
UTILIZATION OF EACH THERAPY CLASS BY SEX AND AGE
CENTRAL NERVOUS SYSTEM
This section examines the percentage of prescriptions attributed to members of each sex/age
grouping for each therapy class.11
FIGURE B4
ANTIDEPRESSANTS
%
25
GASTROINTESTINALS
22.5
FIGURE B3
Females
% of Prescriptions
% of Prescriptions
14.2
Males
12.2
12
5
8.4
7.5
6.2
2.6
1.2
0-9
years
2.0
1.8 1.1
0.8 0.5
10-19
years
20-29
years
30-39
years
40-49
years
50-59
years
60-69
years
70-79
years
80+
years
1.5 1.1
0.7
FIGURE B5
10-19
years
20-29
years
30-39
years
40-49
years
50-59
years
60-69
years
70-79
years
80+
years
ANTIANXIETY AGENTS
%
25
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
17.3
15
10.8
9.1
10
8.4
5.4
5
8.4
4.8
3.4
0.7 0.7
1.0 0.8
0-9
years
10-19
years
3.8
2.2
1.7
1.5
0.8
0
20-29
years
30-39
years
40-49
years
50-59
years
60-69
years
70-79
years
80+
years
Over two-thirds of all prescriptions for antidepressants and antianxiety medications were filled by
females. Women aged 30-59 years accounted for more than half of all antidepressant prescriptions
and for 47.3 percent of all prescriptions for antianxiety drugs. Mental illness is now recognized as
a significant cause of disability in the United States. More than 20 percent of adults and up to
10 percent of children and adolescents suffer from disorders such as depression, anxiety and
135
APPENDIX B
134
19.5
Males
APPENDIX A
11 95 percent confidence interval calculations indicate that for each of the sample percentages (in every therapy class
examined), there is a 95 percent probability that the corresponding percentage value in the entire ESI Drug Trend database lies within +/-1.3 percentage point of the sample percentages.
12 National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK). National Digestive Diseases Information
Clearinghouse. Digestive Diseases Statistics. February 1995. NIH Publication No. 99-3873.
13 American College of Gastroenterology (ACG). Common GI Problems: Volume I www.acg.gi.org/acgdev/patientinfo/frame_giproblems.html
14 Pimentel M., et al. Eradication of Small Intestinal Bacterial Overgrowth Reduces Symptoms of Irritable Bowel Syndrome.
Americal Journal of Gastroenterology 2000. 95(12):3503-3506.
Females
20
ACTIONS
Fifty-six percent of prescriptions for gastrointestinals were filled by females and 44 percent
were filled by males. The bulk of prescriptions in this class were filled by members 30-79 years
of age. The term “digestive disorders” describes a wide range of conditions that vary in both
duration and severity. An estimated 95 million Americans suffer from some kind of digestive
disorder, resulting in nearly 10 million hospitalizations and 50 million visits to physicians’
offices each year and accounting for as much as $107 billion annually in total healthcare costs.12,13
Gastroesophageal reflux disease (GERD), ulcers and colorectal cancer are responsible for a
significant portion of these expenses. Reports suggest that irritable bowel syndrome (IBS) is
now the most commonly diagnosed digestive disorder in the United States. Although up to
30 percent of the population may be affected by IBS, treatment options for this disorder
remain limited.14
% of Prescriptions
COST
FORECAST
2.9
1.9
0
3.7 3.4
0.7 0.7
5.8
0.3 0.5
6
3
2.6 2.5
6.9
4.9
DRUG
IMPORTANCE
DRUG
IMPORTANCE
8.2
COST
FORECAST
ACTIONS
10
5.6
9
0-9
years
APPENDIX A
13.7
15
10.7
6.8
17.6
TRENDS IN
EXPENDITURES
TRENDS IN
EXPENDITURES
16.6
Females
0
APPENDIX B
Males
20
%
18
INTRODUCTION
INTRODUCTION
GASTROINTESTINALS
15
PREFACE
PREFACE
TABLE OF
CONTENTS
TABLE OF
CONTENTS
22501_appB
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Page 136
schizophrenia in a given year. Yet, nearly two-thirds of these individuals fail to receive proper
treatment. Some forms of mental illness are surfacing at an earlier age than ever before.15,16
Unfortunately, the burden of mental illness in terms of personal suffering and lost productivity
will increase if these trends continue.
FIGURE B8
BETA BLOCKERS
%
18
15
INTRODUCTION
ANTIHYPERTENSIVES
%
20
19.3
Females
Males
5.7
6
4.8
3.3
3
0.1 0.1
0.4 0.3
1.1 0.7
0-9
years
10-19
years
20-29
years
1.8 1.6
0
9.6
9.1
30-39
years
40-49
years
50-59
years
60-69
years
70-79
years
80+
years
5.2
4.1
3.8
2.4
0.5 0.6
0-9
years
10-19
years
20-29
years
1.6 1.7
COST
FORECAST
0
30-39
years
40-49
years
50-59
years
60-69
years
70-79
years
80+
years
FIGURE B7
CALCIUM BLOCKERS
16.8 16.8
15
Males
11.8
12
12.3
9.6 10.1
9
5.6 5.7
6
2.6 2.8
3
0
0.1 0.1
0-9
years
10-19
years
0
2.8
ACTIONS
Less than 30 percent of Americans with high blood pressure receive adequate treatment,
though, which may explain why the number of deaths due to high blood pressure is increasing.17
A continuing long-term study funded by the National Heart, Lung, and Blood Institute (NHLBI)
is comparing the efficacy of diuretics with ACEIs and calcium blockers for treatment of high blood
pressure in patients with co-existing conditions such as high cholesterol or diabetes.
An early analysis found the alpha-adrenergic blocker used in this study to be less effective
than standard diuretic therapy in preventing adverse cardiovascular events like congestive
heart failure, causing this portion of the study to be discontinued early.18
Females
DRUG
IMPORTANCE
18
The antihypertensive therapy class was one of only a few classes in which males filled more
prescriptions than females (56.4 percent versus 43.6 percent). Almost 80 percent of all prescriptions
in the antihypertensive class, which includes angiotensin converting enzyme inhibitors (ACEIs),
angiotensin receptor blockers (ARBs) and alpha-adrenergic blockers, were filled by members
between the ages of 40-69 years. The percentage of prescriptions attributable to males and
females was approximately equal for two other classes of cardiovascular drugs — calcium blockers
and beta blockers. Like antihypertensives, these drugs were used primarily by members aged
40 years and older.
COST
FORECAST
0.1 0.3
0.1 0.5
TRENDS IN
EXPENDITURES
% of Prescriptions
9
12.0
5
% of Prescriptions
10.3
10.1
3.9
13.1
10
11.7
11.2
12
16.0
15
DRUG
IMPORTANCE
Males
INTRODUCTION
% of Prescriptions
FIGURE B6
TRENDS IN
EXPENDITURES
16.5 16.6
Females
CARDIOVASCULAR
ACTIONS
PREFACE
PREFACE
TABLE OF
CONTENTS
TABLE OF
CONTENTS
22501_appB
1.9
0.5 0.5
30-39
years
40-49
years
50-59
years
60-69
years
70-79
years
80+
years
15 U.S. Public Health Service, Department of Health and Human Services. Report of the Surgeon General’s Conference on
Children’s Mental Health: A National Action Agenda. Washington, DC. 2000. ISBN No. 0-16-050637-9. www.surgeongeneral.gov/cmh/childreport.htm Accessed March, 2001.
16 National Institute of Mental Health (NIMH) Statistics: The Number Count. Mental Disorders in America. September 2000.
Updated January, 2001. www.nimh.nih.gov/publicat/numbers.cfm Accessed March, 2001.
136
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
17 American Heart Association. High Blood Pressure Statistics www.americanheart.org/hbp/phys_stats.html
Accessed March, 2001.
18 National Heart, Lung and Blood Institute, National Institutes of Health. NIH News Release. NHLBI Stops Part
of Study — High Blood Pressure Drug Performs No Better Than Standard Treatment. March 2000.
www.nhlbi.nih.gov/new/press/mar08-00.htm Accessed March, 2001.
137
APPENDIX B
APPENDIX B
20-29
years
APPENDIX A
APPENDIX A
0
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TABLE OF
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TABLE OF
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22501_appB
FIGURE B9
INFLAMATION AND PAIN MANAGEMENT
ANTIHYPERLIPIDEMICS
FIGURE B10
Males
14.9
15
14.9
11.1
10
4.6 5.5
2.9
0 0.1
10-19
years
0.2 0.3
20-29
years
1.3
30-39
years
1.1 1.1
40-49
years
11.0
9.6
10
6.5
5
15.3
Males
15
12.7
0 0
0-9
years
17.2
Females
% of Prescriptions
% of Prescriptions
50-59
years
60-69
years
70-79
years
3.6
2.6
2.2
1.4
1.2 0.8
0.2 0.2
0-9
years
10-19
years
20-29
years
30-39
years
40-49
years
50-59
years
60-69
years
70-79
years
80+
years
FIGURE B11
NARCOTIC ANALGESICS
%
18
16.6
COST
FORECAST
Females
15
13.0
Males
11.9
12
8.7
9
11.5
8.5
6.6
6
4.8
4.1
3.7
2.6 2.2
3
2.0
0.6 0.7
0-9
years
10-19
years
20-29
years
30-39
years
40-49
years
50-59
years
60-69
years
70-79
years
0.8 0.5
80+
years
APPENDIX A
APPENDIX A
ACTIONS
ACTIONS
0
1.4
DRUG
IMPORTANCE
19 National Cholesterol Education Program. Second Report of the Expert Panel on Detection, Evaluation, and Treatment of
High Blood Cholesterol in Adults (Adult Treatment Panel II). September 1993. NIH Publication No. 93-3096.
20 Abookire SA, et al. Use and Monitoring of “Statin” Lipid-Lowering Drugs Compared With Guidelines. Arch Intern Med.
2001;161:53-58.
21 American Heart Association (AHA) News Release. American Heart Association journal report: Pravastatin Reduces Risk Of
Diabetes, Stroke. January, 2001. www.americanheart.org/Whats_News/AHA_News_Releases/01-22-01_comment1.html
Accessed February, 2001.
138
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
139
APPENDIX B
APPENDIX B
TRENDS IN
EXPENDITURES
DRUG
IMPORTANCE
6.3
5.4
4.3
2.1
0
Sixty percent of antihyperlipidemic prescriptions were filled by males. Use of these drugs was
minimal among members younger than 40 years of age. The benefit of using the cholesterollowering drugs commonly referred to as statins for primary and secondary prevention of heart
attacks is well documented.19 However, a recent study found these agents to be widely misused
based on criteria from the National Cholesterol Education Program (NCEP) treatment guidelines.20
New evidence suggests at least one type of statin can also reduce the risk of Type 2 diabetes and
stroke, although additional studies are needed to determine if other drugs in this class provide
the same benefit.21
8.5
8.3
5
80+
years
% of Prescriptions
INTRODUCTION
20
INTRODUCTION
TRENDS IN
EXPENDITURES
%
20
Females
0
COST
FORECAST
ANTI-RHEUMATICS
22.9
PREFACE
PREFACE
%
25
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TABLE OF
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22501_appB
FIGURE B12
RESPIRATORY
MIGRAINE PRODUCTS
FIGURE B13
% of Prescriptions
12
Females
19.6
18.1
20
15
10
8.0
2.9
5
0-9
years
3.4
1.3
10-19
years
5.1
3.5
3.1
1.1
20-29
years
30-39
years
40-49
years
50-59
years
1.3
60-69
years
0.4 0.2
70-79
years
0
0.1
8.5
8
6
7.2
6.9
5.3
4.9
7.1
4.0
4
3.3
2.8
2.5
0
0.8 1.1
10-19
years
20-29
years
30-39
years
40-49
years
60-69
years
70-79
years
DRUG
IMPORTANCE
ANTIHISTIMINES
14.8
13.2
Males
% of Prescriptions
7.2
5.1
5.6
6.2
4
6.9
5.8
ACTIONS
10.4
8
6.3
5.2
4.8
2.9
2.6
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
10-19
years
20-29
years
30-39
years
40-49
years
50-59
years
60-69
years
70-79
years
80+
years
25 Office of the Assistant Secretary for Planning and Evaluation, Department of Health and Human Services. Action Against
Asthma: A Strategic Plan for the Department of Health and Human Services. May 2000.
http://aspe.hhs.gov/sp/asthma/index.htm#toc Accessed March, 2001.
141
APPENDIX B
140
0-9
years
0.5 0.2
APPENDIX A
0
COST
FORECAST
FIGURE B14
1.3 1.1
22 American Association of Neurological Surgeons, Congress of Neurological Surgeons. Chronic Pain: Frequently Asked
Questions. 1998. www.neurosurgery.org/pubpages/patres/faq_chronicpain.html
23 The American Occupational Therapy Association, Inc (AOTA). Consumer Fact Sheet. Managing Daily Life When Dealing
With Chronic Pain. www.aota.org/featured/area6/links/link02i.asp Accessed March, 2001.
24 Joint Commission on Accreditation of Healthcare Organizations (JCAHO). Standards Revisions for 2001. Pain Management
Standards for 2001. www.jcaho.org/standard/stds2001_mpfrm.html Accessed February, 2001.
80+
years
Antiasthmatic drugs were one of the therapy classes used frequently by children. Among members
younger than 20 years of age, males accounted for a larger proportion of antiasthmatic prescriptions
than females. Throughout the middle years, more antiasthmatic prescriptions were attributable
to females. Among members 70 years and older, males once again were responsible for the majority
of prescriptions in this class. Despite recent advances in the diagnosis and treatment of asthma,
prevalence rates continue to rise. Current research focuses on understanding the cause of asthma
and identifying a genetic basis for susceptibility in hopes that asthma will one day be preventable.
In the meantime, efforts are aimed at increasing awareness of and promoting adherence to
established treatment guidelines, improving asthma surveillance and providing increased access
to medical care — particularly among high-risk populations.25
%
16
ACTIONS
50-59
years
TRENDS IN
EXPENDITURES
0-9
years
12
APPENDIX A
6.1
4.6
Females
APPENDIX B
6.6
6.1
2
80+
years
Females accounted for approximately 60 percent of prescriptions for both anti-rheumatics and
narcotic analgesics. Anti-rheumatics, however, were generally used somewhat later in the life
span than were narcotic analgesics. Eighty-four percent of prescriptions for migraine drugs were
filled by females, with women aged 30-59 years accounting for the majority of these prescriptions. Approximately 80 million Americans suffer from chronic pain and the actual count may be
as much as 60 percent higher by some estimates.22,23 Chronic pain, regardless of the source, alters
the physical and mental well-being of an individual and may potentially lead to permanent disability. Practice standards like those recently developed by the Joint Commission on Accreditation
of Healthcare Organizations (JCAHO) for the assessment and management of pain in hospitals
and other healthcare settings are an important step toward improving pain management practices. These standards emphasize the need to assess pain in all patients, educate patients about
pain and the available treatment options and provide an individualized treatment plan. A number
of issues related to end-of-life care are also addressed.24
10
11.5
10.9
Males
INTRODUCTION
TRENDS IN
EXPENDITURES
Males
25
0.2 0.1
COST
FORECAST
%
14
% of Prescriptions
PREFACE
30
0
DRUG
IMPORTANCE
Females
31.6
PREFACE
INTRODUCTION
ANTIASTHMATICS
%
35
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22501_appB
ANTI-INFECTIVES
FIGURE B15
DECONGESTANTS
FIGURE B17
PENICILLINS
15.0
Females
15
7.2
6
3
5.1
6.0
5.1
4.5
3.6
7.3
2.5
3.9
1.0 0.9
0-9
years
10-19
years
20-29
years
30-39
years
40-49
years
50-59
years
60-69
years
70-79
years
0.3 0.2
% of Prescriptions
% of Prescriptions
7.2
8.6
6.6
5.5
5.1
5.9
4.3
3.3
2.0 1.8
0-9
years
10-19
years
20-29
years
30-39
years
40-49
years
50-59
years
60-69
years
0.7 0.6
0.2 0.2
70-79
years
80+
years
FIGURE B16
COUGH/COLD
%
18
FIGURE B18
%
14
12.5
12
12.3
11.1
12
9
6
7.3
5.1
6.0
5.1
7.2
7.7
3.9
3.6
2.5
1.0 0.9
0-9
years
10-19
years
20-29
years
30-39
years
40-49
years
Males
50-59
years
60-69
years
70-79
years
0.3 0.2
80+
years
7.6
8
6.5
6.1
6.7
6.1
6.5
6
5.1
3.9
4
2.8 2.7
2
1.0 0.9
0-9
years
10-19
years
20-29
years
30-39
years
40-49
years
50-59
years
60-69
years
70-79
years
0.3 0.4
80+
years
ACTIONS
APPENDIX A
The antihistamine, decongestant and cough/cold therapy classes were characterized by relatively
high use among young people and greater use by females than males, particularly in the years
following childhood. The average adult will experience two to four colds per year, and the average
child may have as many as eight. Primarily occurring between the months of September and May,
cold symptoms — including a runny nose, nasal congestion, coughing and sneezing — typically
last about a week. The numerous varieties of viruses that cause the common cold can make some
individuals more susceptible to other, more serious infections involving the lungs, inner ear or
nasal passages.26
10.6
9.8
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
143
APPENDIX B
26 American Lung Association. What is a Cold? 2001. www.lungusa.org/diseases/c&fguide/cold.html#how
Accessed March 2001.
142
DRUG
IMPORTANCE
3
0
Females
10.8
10
6.1
4.5
COST
FORECAST
% of Prescriptions
CEPHALOSPORINS
15.0
Males
TRENDS IN
EXPENDITURES
ACTIONS
6.4
5
0
APPENDIX A
8.9
10
0
Females
APPENDIX B
Males
80+
years
% of Prescriptions
INTRODUCTION
9
Females
15
6.1
INTRODUCTION
TRENDS IN
EXPENDITURES
7.7
12.5
15
COST
FORECAST
17.4
15.6
12
0
DRUG
IMPORTANCE
%
20
11.1
Males
PREFACE
PREFACE
%
18
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CONTENTS
TABLE OF
CONTENTS
22501_appB
FIGURE B19
FIGURE B20
MACROLIDES
ORAL CONTRACEPTIVES
%
14
7.4
7.9
6.8
6.6
5.8
6
% of Prescriptions
% of Prescriptions
8.6
6.8
5.1
3.7
3.3
4
20-29
years
30-39
years
40-49
years
50-59
years
60-69
years
70-79
years
0
80+
years
8.7
0.1 0.1
0-9
years
0.3
0.2
10-19
years
20-29
years
0.2
40-49
years
1.4
0
50-59
years
0 0
60-69
years
0 0
70-79
years
0
0
80+
years
FIGURE B21
ESTROGENS
%
60
51.1
Females
50
Males
40
30
23.1
17.2
20
10
0
0
0-9
years
0.1 0
10-19
years
0.3
0
20-29
years
3.3
0.1
30-39
years
0.2
40-49
years
0.5
50-59
years
3.2
0.2
60-69
years
0.1
0.7
70-79
years
0
80+
years
APPENDIX A
144
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
29 American College of Obstetrics and Gynecology (ACOG). Press Release. ACOG Issues Guidelines On Diagnosis And
Treatment Of PMS. March 2000. www.acog.org/from_home/publications/press_releases/nr03-31-00-1.htm
Accessed March, 2001.
145
APPENDIX B
27 Assistant Secretary for Legislation (ASL). Department Of Health and Human Services (DHHS). Hearing On Antimicrobial
Resistance. Role of NIH in Meeting the Public Health Needs in Antimicrobial Resistance. September 2000.
www.hhs.gov/asl/testify/t000920a.html Accessed March, 2001.
28 National Institute of Allergy and Infectious Diseases (NIAID) Fact Sheet: Antimicrobial Resistance. June 2000
www.niaid.nih.gov/factsheets/antimicro.htm Accessed March, 2001.
APPENDIX A
Women of childbearing age accounted for the majority of prescriptions filled for oral contraceptives,
while women of menopausal age were responsible for most estrogen use. Premenstrual Syndrome
(PMS), which has been associated with fluctuating hormones levels in women, continues to gain
recognition as a legitimate health concern. An estimated 5 percent-10 percent of menstruating
women suffer from severe physical and emotional symptoms while a much greater number experience lesser degrees of discomfort. In recently released guidelines for the diagnosis and treatment
of PMS, the American College of Obstetricians and Gynecologists addresses the use of hormonal
therapy and various other treatment options.29 Reproductive health issues have also received
ACTIONS
ACTIONS
0.3
30-39
years
DRUG
IMPORTANCE
Like those therapy classes used to treat respiratory conditions, the anti-infective classes
showed high use by younger members. The percentage of prescriptions filled by males and
females was similar within the first two age groups but was relatively greater for females after
childhood. Although widespread resistance to antibiotic therapy is quickly becoming a reality,
physicians’ prescribing habits have been slow to change. According to the Centers for Disease
Control and Prevention (CDC), nearly 50 percent of the 100 million antibiotic prescriptions written
each year in the United States are unnecessary or inappropriate.27 Bacterial pneumonia, gonorrhea
and childhood ear infections have become more difficult to treat as the bacteria that commonly
cause these conditions have developed resistance to the drugs that are commonly used to treat
them. The financial impact of dealing with antibiotic-resistant infections may be as high as
$30 billion annually.28
0
APPENDIX B
14.6
15
5
0.2 0.2
% of Prescriptions
COST
FORECAST
10-19
years
20
COST
FORECAST
DRUG
IMPORTANCE
0.9 0.8
0-9
years
25
TRENDS IN
EXPENDITURES
TRENDS IN
EXPENDITURES
2
Males
30
10
2.1
0
Females
34.9
35
9.2
INTRODUCTION
INTRODUCTION
39.3
40
11.5
Males
10
8
%
45
12.9
Females
12
PREFACE
PREFACE
WOMEN’S HEALTH
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2:42 PM
Page 146
OTHER
PREFACE
and accounts for more than $100 million in spending for over-the-counter products alone. Forty percent of all acne cases are severe enough to warrant not only a physician’s care but also the use of
one or more prescription drugs. Acne generally resolves within 5 to 10 years, although some cases
persist well into adulthood.34 Psoriasis and eczema represent a group of chronic skin conditions that
can cause persistent physical discomfort and, in severe cases, may lead to permanent disfigurement.
Each affects more than 5 percent of the population and generally requires long-term treatment.
Psoriasis accounts for about $3.2 billion in healthcare spending each year and eczema has an
equally substantial economic impact.35,36
FIGURE B23
INTRODUCTION
significant attention as the national rate of unintended pregnancies remains near 49 percent.30
However, decisions concerning the availability of emergency contraception and the non-surgical
termination of pregnancy are influenced strongly by social factors as well as by scientific
research. Numerous studies have looked at the role of estrogen in preventing heart disease in
postmenopausal women. Now evidence suggests a link between sudden heart attacks in younger
women and the decrease in estrogen that occurs during a woman’s normal menstrual cycle.31
Given the fact that more women in the United States die from heart disease and stroke than from
any other cause, additional studies on the effects of estrogen and the use of hormone replacement therapy are likely.32
PREFACE
INTRODUCTION
TABLE OF
CONTENTS
TABLE OF
CONTENTS
22501_appB
ANTIDIABETICS
FIGURE B22
%
25
% of Prescriptions
8.6
8
DRUG
IMPORTANCE
6.5
5.8
5.7
6
4.4 4.3
4.1
1.3 1.5
2
10-19
years
20-29
years
30-39
years
40-49
years
50-59
years
60-69
years
70-79
years
0.2 0.2
0-9
years
0.7 0.8
1.2 1.1
10-19
years
20-29
years
3.4
0.9
30-39
years
40-49
years
50-59
years
60-69
years
70-79
years
0.0
80+
years
Males were responsible for more antidiabetic prescriptions than females overall, although
differences were relatively modest between the sexes within each age category. Most prescriptions
in this class were dispensed to adults aged 40 through 69 years. According to the American
Association of Clinical Endocrinologists (AACE), more than 60 million Americans are at risk for
developing Type 2 diabetes because they are overweight and they already have some degree of
insulin resistance. Even more disheartening, the prevalence of Type 2 diabetes is increasing
among children. Unfortunately, the risk of experiencing serious medical complications increases
with the length of time that diabetes is present.37 In January, the AACE released updated diabetes
treatment guidelines to address the use of new drugs, stress the role of proper nutrition and physical activity and promote intensive diabetes self-management. These guidelines underscore the
importance of actively taking control of blood sugar levels by people with diabetes.38
147
APPENDIX B
34 American Academy of Dermatology. AcneNet. Basic Facts about Acne. 2000. www.derm-infonet.com/acnenet/basfact.html
Accessed March, 2001.
35 National Psoriasis Foundation (NPS). About Psoriasis – FAQs. www.psoriasis.org/b500.htm Accessed February, 2001.
36 American Academy of Dermatology. EczemaNet. What is Eczema? 2000.
www.skincarephysicians.com/eczemanet/whatIs.html Accessed February, 2001.
37 American Medical Association. AMA News. Children Now Developing the Type of Diabetes Previously Seen Only in
Adults. January 2001. www.medem.com/MedLB/article_detaillb.cfm?article_ID=ZZZLN04C3IC&sub_cat=100
Accessed March, 2001.
38 American Association of Clinical Endocrinologists Online: Publications. The Press Room. Physicians Warn that Obesity is
Driving Type 2 Diabetes Epidemic: New Guidelines Urge 60 Million Americans with Insulin Resistance to Know Their
GlucoseAverage™. November 1999. www.aace.com/pub/press/diabetes110199.html Accessed March, 2001.
APPENDIX A
30 National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention,
Department of Health and Human Services. Chronic Disease Prevention. Women’s Reproductive Health. June 1999.
www.cdc.gov/nccdphp/women.htm Accessed February, 2001.
31 American Heart Association (AHA) News Release. American Heart Association journal report: Low Estrogen Linked to Heart
Attack in Premenopausal Women. www.americanheart.org/Whats_News/AHA_News_Releases/11-14-00_1-comment.html
Accessed March, 2001.
32 American Heart Association (AHA) Biostatistical Fact Sheet —- Populations Women and Cardiovascular Diseases.
www.americanheart.org/statistics/biostats/biowo.htm Accessed March, 2001.
33 American Academy of Dermatology (AAD) Press Release. American Academy of Dermatology Issues Patient Alert:
Misdiagnosis of Skin Cancer Can Be Fatal. April 2000. www.aad.org/PressReleases/misdiagnosis.html
Accessed March, 2001.
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
5.1
3.2 3.6
80+
years
Dermatologicals were used frequently by members in the second youngest age group. Before age 20
and after age 59, the percentages of males and females using these drugs were similar. Throughout
mid-life, however, females were responsible for the majority of dermatological prescriptions. Most
Americans will experience some type of skin condition — ranging from possibly deadly to relatively
minor — during their lifetimes. For example, each year in the United States, approximately 1.3 million new cases of skin cancer are diagnosed — including about 48,000 cases of melanoma, a
potentially fatal form of skin cancer that has been linked to excessive sun exposure.33 Far less serious but much more widespread, acne affects nearly all adolescents between 12 and 17 years of age,
146
9.3
9.3
10
0
0.6 0.5
0-9
years
13.4
11.5
5
3.4 3.6
4
15.4
15
ACTIONS
ACTIONS
Males
8.3
19.7
Males
DRUG
IMPORTANCE
APPENDIX A
Females
9.6
% of Prescriptions
10.4
20
10.4
10
0
APPENDIX B
Females
11.0
COST
FORECAST
COST
FORECAST
%
12
TRENDS IN
EXPENDITURES
TRENDS IN
EXPENDITURES
DERMATOLOGICALS
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ANTICANCER
PREFACE
25.1
Females
25
% of Prescriptions
10
7.2
4.7
5
2.5
0.5 0.5
0-9
years
0.7
0.7 0.6
10-19
years
20-29
years
5.7
4.4
5.9
3.7
2.2
30-39
years
2.0 1.4
40-49
years
50-59
years
60-69
years
70-79
years
80+
years
% of Prescriptions
Males
Females
14.2 13.6
Males
10.6
10.0
8.5
9
6.8
6
3.9
0
15.2 15.6
12.5
12
4.5
4.2
5.1
4.5
3.6
2.5
1.6 1.8
0-9
years
2.0
1.0 0.8
10-19
years
20-29
years
30-39
years
40-49
years
50-59
years
60-69
years
70-79
years
80+
years
12
8.7
9
6
3
8.4 8.1
4.3
2.6
1.2 0.8
0-9
years
2.3 2.3
1.4
10-19
years
0.5 0.6
20-29
years
30-39
years
40-49
years
50-59
years
60-69
years
70-79
years
0.1 0.2
80+
years
148
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
149
APPENDIX B
39 U.S. Department of Health and Human Services. Healthy People 2010, 2nd ed. Volume I. Understanding and Improving
Health: Cancer. November 2000. www.health.gov/healthypeople/document/html/volume1/03Cancer.htm
Accessed March, 2001.
40 Centers for Disease Control and Prevention. HIV/AIDS Surveillance Report. 2000;20(1):1-44.
41 The Panel on Clinical Practices for the Treatment of HIV Infection. Guidelines for the Use of Antiretroviral Agents in HIVInfected Adults and Adolescents. U.S. Department of Health and Human Services (DHHS) and The Henry J. Kaiser Family
Foundation. February 2001. http://hivatis.org/guidelines/adult/Feb05-01/pdf/AAFEB05B.PDF Accessed March, 2001.
42 The Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children, National Pediatric and
Family HIV Resource Center (NPHRC), Health Resources and Services Administration (HRSA), and the National Institutes
of Health (NIH). Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection. January 2000.
http://hivatis.org/guidelines/pediatric/Jan07-00/Text/ped_12.pdf Accessed March, 2001.
APPENDIX A
APPENDIX A
0
APPENDIX B
16.1
Females
15
3
%
18
15
%
18
ACTIONS
ACTIONS
ANTIVIRALS
ANTICONVULSANTS
DRUG
IMPORTANCE
DRUG
IMPORTANCE
FIGURE B25
FIGURE B26
COST
FORECAST
Three out of every four prescriptions for anticancer drugs were filled by females. Individuals in their
40s, 50s and 60s accounted for the majority of prescriptions in this therapy class. Cancer remains
one of the leading causes of death in the United States, second only to heart disease. More than
1.2 million new cases of cancer and 550,000 cancer-related deaths were projected for 2000, with
costs in excess of $107 billion. The good news is the overall incidence of cancer appears to be
declining. Moreover, regular cancer screenings have lead to the early detection and successful
treatment of many common types of cancer. As a result, the five-year survival rate for all cancers
combined is now at 60 percent — an increase of more than 10 percent over the last 25 years.39
TRENDS IN
EXPENDITURES
TRENDS IN
EXPENDITURES
13.5
15
0
COST
FORECAST
19.0
INTRODUCTION
INTRODUCTION
Males
20
PREFACE
%
30
Females aged 20 to 29 years accounted for twice as many prescriptions for antivirals as males
in the same age range. In other age groups, the proportion of antiviral prescriptions attributable
to males and females was similar. Almost 90 percent of prescriptions in this class were filled
by members aged 20-59 years. Nearly 20 years have passed since the AIDS epidemic first began.
During this time, advances in AIDS research have lead to the development of drugs and treatment
strategies that have greatly prolonged life in many people infected with the human immunodeficiency virus (HIV). Now, more than 320,000 Americans are living with AIDS.40 Regrettably, drugresistance is increasing in frequency among newly infected individuals, and concern is growing
over the long-term effects of therapy. Guidelines developed in 1998 by an expert panel on the
treatment of HIV infection have recently been updated to focus on these important issues.
Included in this update are evidence-based recommendations on when to initiate drug therapy
based on an individual’s immune status and viral load — a measure of how much the virus has
spread.41 Pediatric treatment guidelines have also been updated to include the use of new drugs
and the prevention of perinatal HIV transmission.42
% of Prescriptions
FIGURE B24
6/4/01
2:42 PM
Page 150
PREFACE
(Please copy and fax or mail back.)
Quantity
1999 Drug Trend Report – June 2000 ($100 per copy)
Subtotal
Shipping & Handling (add $3 for each additional copy)
MO residents add 5.975% sales tax
Total
ANTIFUNGALS
Females
% of Prescriptions
TRENDS IN
EXPENDITURES
Discounts available for volume orders; call for information.
20
19.8
19.5
Males
15
PAYMENT
13.5
13.0
10
4.7
3.6
2.2
0-9
years
1.7
10-19
years
5.7
4.9
Check enclosed payable to Express Scripts, Inc.
❑
Money order enclosed
❑
Credit card
3.9
❑ MasterCard
2.3
2.1
20-29
years
❑
30-39
years
40-49
years
50-59
years
60-69
years
0.9 0.6
0.2 0.1
70-79
years
80+
years
Exp. Date
/
❑ Visa
❑ Discover
Signature
DRUG
IMPORTANCE
SHIPPING ADDRESS (PLEASE PRINT)
Name
Title
Organization
Shipping Address
Telephone
Fax
ACTIONS
Most antifungal prescriptions were filled by females, particularly those aged 20-59 years.
Systemic fungal infections are increasingly more common, especially within the hospital setting.
Factors that contribute to the growing prevalence of fungal infections include age, the presence
of underlying disease and the widespread use of antimicrobial drugs — all of which affect the
immune system’s ability to function properly. Those most at risk for developing serious or potentially
life-threatening fungal infections include organ transplant recipients, newborns and individuals
who have cancer or AIDS.45 To complicate matters, many types of fungi are becoming resistant to
treatment with available drugs.46
Account No.
COST
FORECAST
1.4
0
$7
TRENDS IN
EXPENDITURES
COST
FORECAST
Amount
2000 Drug Trend Report – June 2001 ($150 per copy)
FIGURE B27
5
DRUG
IMPORTANCE
Item
INTRODUCTION
The largest percentage of anticonvulsant prescriptions was dispensed to middle-aged members,
those 30-59 years old. Within these age ranges, females accounted for a greater percentage of
claims than males. There was little difference between the sexes for the remaining age groups.
Ten percent of Americans experience a least one seizure during their lifetime and nearly 3 percent
are diagnosed with a seizure disorder such as epilepsy. Seizure disorders account for about
$12.5 billion in direct and indirect medical costs.43 Experts suggest that up to 80 percent of
seizure-prone individuals can lead normal, productive lives if properly treated.44 Unfortunately,
many either fail to achieve complete seizure control or experience side effects that significantly
reduce their quality of life.
PREFACE
INTRODUCTION
EXPRESS SCRIPTS DRUG TREND REPORT
%
25
ACTIONS
TABLE OF
CONTENTS
TABLE OF
CONTENTS
22501_appB
APPENDIX B
150
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
Information: 800.281.0712
151
APPENDIX B
43 Centers for Disease Control and Prevention (CDC), National Center for Chronic Disease Prevention and Health Promotion,
U.S. Department of Health and Human Services. Chronic Disease Prevention. Epilepsy. January 2001. www.cdc.gov/nccdphp/epilepsy.htm Accessed March 2001.
44 World Health Organization. Mental Health And Brain Disorders. 2000.
www.who.int/mental_health/Topic_Epilepsy/Epilespy1.htm Accessed March, 2001.
45 Powderly WG. Emerging fungi — resistant, resilient, and not so rare. Presented at the 38th Annual Meeting of the
Infectious Diseases Society of America. September 2000.
www.medscape.com/medscape/CNO/2000/IDSA_CS/IDSA-03.html Accessed February, 2001.
46 Dismukes WE. Introduction to antifungal drugs. Clinical Infectious Diseases. 2000;30:653-657.
Fax: 314.702.7059
Mail: Express Scripts Drug Trend Report
Express Scripts, Inc.
13900 Riverport Drive
Maryland Heights, MO 63043
APPENDIX A
APPENDIX A
TO ORDER:
EXPENDITURES
COST
FORECAST
DRUG
IMPORTANCE
TRENDS IN
FORECAST
INTRODUCTION
TRENDS IN
EXPENDITURES
COST
ACTIONS
PREFACE
INTRODUCTION
ACTIONS
APPENDIX A
APPENDIX A
PREFACE
APPENDIX B
APPENDIX B
TABLE OF
CONTENTS
TABLE OF
CONTENTS
N OT E S
N OT E S
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EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
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APPENDIX B
APPENDIX A
ACTIONS
DRUG
IMPORTANCE
COST
FORECAST
TRENDS IN
EXPENDITURES
INTRODUCTION
PREFACE
TABLE OF
CONTENTS
22501_appB
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N OT E S
EXPRESS SCRIPTS, INC. 2000 DRUG TREND REPORT
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