Download Hospital Pharmacy Strategies for REMS Objectives REMS

10/18/2010
Objectives
Hospital Pharmacy Strategies
for REMS
SCSHP Fall Meeting
October 28, 2010
John Pearson, PharmD, BCNSP, BCPS
Manager, Pharmacy Clinical Services
Greenville Hospital System University Medical Center
REMS: Definition
Risk
Evaluation and
Mitigation
Strategies
Medication safety program developed by the
FDA as part of the FDA Amendment Act
(FDAAA) of 2007
RiskMAPs
High risk medications requiring additional
safety processes
• Define and describe REMS
• Differentiate between REMS, black box
warnings, controlled access programs and
patient education requirements
• Review the current medications that
require a REMS
• Review strategies hospital pharmacies can
implement to comply with REMS
requirements
Evolution of FDA Drug Safety
Programs
Patient Education Guides/PPI - Estrogen
Clozaril Patient Management System - 1980s
Risk Minimization Action Plans (RiskMAPs) 2002 – Isotretinoin, thalidomide
Evolution of FDA Drug Safety
Programs
Institute of Medicine 2006: “The Future of
Drug Safety: Promoting and Protecting the
Health of the Public”
P t off approvall process – Risk/Benefit
Part
Ri k/B
fit
May have restricted distribution system
Critical of FDA for medications withdrawn
from the market due to safety
•Clarify FDA authority on postmarket monitoring
Shane R. Am J Health Syst Pharm. 2009 Dec 15;66(Suppl 7):S6-12.
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FDAAA 2007
FDA Authority - REMS
Title IX – Enhanced Authorities Regarding
Postmarket Safety of Drugs
Pre and Post Marketing Implementation
Reassessment – 18 months, 3 and 7 years
Sec. 901.
S
901 Postmarket
P t
k t studies
t di and
d clinical
li i l
trials regarding human drugs; risk evaluation
and mitigation strategies.
Sec. 902. Enforcement
http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=110_cong_public_laws&docid=f:publ085.110 (Accessed 09/18/2010)
FDAAA 2007
To REMS or Not To REMS
Considerations in Determining the Need for Risk Evaluation and
Mitigation Strategies before FDA Approval of a Drug Product
•
•
•
•
•
•
Estimated size of the population likely to use the drug
Seriousness of the disease or condition for which the drug will be
used
Expected benefit from the drug with respect to the disease or
condition
Expected or actual duration of treatment with the drug
Seriousness of any known or potential adverse events related to use
of the drug and background rate of such events in the population
likely to use the drug
Whether the drug is a new molecular entity
Enforcement - $250,000/violation
$1 million maximum per single proceeding
Prevent sale of drug
Shane R. Am J Health Syst Pharm. 2009 Dec 15;66(Suppl 7):S6-12.
Components of a REMS
Medication Guides or Patient Package
Inserts
Communication
C
i ti plan
l tto h
health
lth care
providers
Elements to assure safe use (ETASU)
Meyer B. Am J Health Syst Pharm. 2009 Dec 15;66(Suppl 7):S3-5.
Elements to assure safe
use (ETASU)
Where are we now?
Black Box Warnings
• Special training, experience, or certification of health care providers
who prescribe the drug
• Special certification of pharmacies, practitioners, or health care
settings that dispense the drug
• Dispensing of the drug to patients only in certain health care
settings such as hospitals
settings,
• Dispensing of the drug to patients with evidence or other
documentation of safe-use conditions, such as laboratory test
results
• Use of special monitoring for each patient receiving the drug
• Enrollment of each patient receiving the drug in a registry
Over 400 medications with black box
warnings
•Nearly doubled in last 3 years
Non-REMS
Combined with REMS programs
Meyer B. Am J Health Syst Pharm. 2009 Dec 15;66(Suppl 7):S3-5.
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10/18/2010
Patient Package Inserts
Patient Package Inserts
Non - REMS
Over 200 medications
Inpatient versus Outpatient?
Non-REMS – Part of labeling
CFR 21 Part 208
Each authorized dispenser of a prescription drug product for which a
Medication Guide is required under this part shall, when the product is
dispensed to a patient (or to a patient's agent), provide a Medication Guide
directly to each patient (or to the patient's agent)
Combined with REMS programs – Not
necessarily part of labeling
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CFRPart=208&showFR=1 (Accessed 09/25/10)
Patient Package Inserts
Non - REMS
Patient Package Inserts
REMS
CFR 21 Part 208
Definitions
(a)Authorized dispenser means an individual licensed, registered, or otherwise
permitted by the jurisdiction in which the individual practices to provide drug
products on prescription in the course of professional practice.
((b)Dispense
) p
to p
patients means the act of delivering
gap
prescription
p
drug
gp
product
to a patient or an agent of the patient either:
(1) By a licensed practitioner or an agent of a licensed practitioner, either
directly or indirectly, for self-administration by the patient, or the
patient's agent, or outside the licensed practitioner's direct
supervision; or
(2) By an authorized dispenser or an agent of an authorized dispenser
under a lawful prescription of a licensed practitioner
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CFRPart=208&showFR=1 (Accessed 09/25/10)
http://www.ashpadvantage.com/fdaaa (Accessed 09/25/10)
RiskMAPs
Restricted Drug Distribution
Systems (RDDS)
Old RiskMAPs originally “grandfathered”
Specialty Pharmacies – High Cost
Abarelix
Alosetron
Ambrisentan
Bosentan
Clozapine
Dofetilide
Eculizumab
Fentanyl PCAa
Isotretinoin
Lenalidomide
Mifepristone
Natalizumab
Smallpox (vaccinia)
vaccine, live
Sodium oxybate
Thalidomide
Only Ambrisentan continued with REMS
Non – REMS
REMS
“Brown Bagging”
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Medications that have a
REMS program
Medications that have a REMS
program
• 151 different REMS programs
•
•
•
•
– 127 require medication guide and/or
communication plan
• 24 have elements to assure safe
medication use
– Long acting opioids – ongoing review
Strategies for hospital
pharmacies
Alvimopan
Ambrisentan
Bosentan
Buprenorphine
transderm/sublingual
• Certolizumab pegol
• Darbepoetin/epoetin
alfa
• Eculizumab
• Lenalidomide
• Olanzapine
Extended-Release
Injection
j
• Romiplastin
• Sacrosidase
• Thalidomide
• Vigabatrin
Strategies – Case Study
ESA - APPRISE
Medications – All erythropoiesis-stimulating
agents (ESAs) include epoetin alfa (Epogen,
Procrit) and darbepoetin (Aranesp)
Assisting Providers and cancer Patients with
Risk Information for the Safe use of ESAs
(ESA APPRISE) Oncology Program
http://www.ashpadvantage.com/fdaaa (Accessed 09/25/10)
https://www.esa-apprise.com/ESAAppriseUI/ESAAppriseUI/default.jsp (Accessed 09/25/10)
Strategies – Case Study
ESA - APPRISE
Strategies – Case Study
ESA - APPRISE
Components of REMS
• medication guides
• communication plan
• elements to assure safe use
• implementation system
• timetable for submission of assessments
of the REMS
Elements to assure safe use (ETASU)
https://www.esa-apprise.com/ESAAppriseUI/ESAAppriseUI/default.jsp (Accessed 09/25/10)
• Special training, experience, or certification of health care providers
who prescribe the drug
pharmacies, practitioners
practitioners, or health care
• Special certification of pharmacies
settings that dispense the drug
• Dispensing of the drug to patients only in certain health care
settings, such as hospitals
• Dispensing of the drug to patients with evidence or other
documentation of safe-use conditions, such as laboratory test
results
• Use of special monitoring for each patient receiving the drug
• Enrollment of each patient receiving the drug in a registry
Meyer B. Am J Health Syst Pharm. 2009 Dec 15;66(Suppl 7):S3-5.
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10/18/2010
Elements to assure safe
use (ETASU)
Strategies – Case Study
ESA - APPRISE
• Special training, experience, or certification of health care providers
who prescribe the drug
• Special certification of pharmacies, practitioners, or health care
settings that dispense the drug
• Dispensing of the drug to patients only in certain health care
settings such as hospitals
settings,
• Dispensing of the drug to patients with evidence or other
documentation of safe-use conditions, such as laboratory test
results
• Use of special monitoring for each patient receiving the drug
• Enrollment of each patient receiving the drug in a registry
ETASU – Detail
Meyer B. Am J Health Syst Pharm. 2009 Dec 15;66(Suppl 7):S3-5.
• Healthcare providers who both prescribe and
dispense (ESAs) for patients with cancer in
private p
p
practice settings
g will be specially
p
y certified
• Healthcare providers who prescribe (ESAs) for
patients with cancer in hospitals will be specially
certified
• Hospitals that dispense (ESAs) for patients with
cancer will be specially certified under
http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM200104.pdf (Accessed 09/25/10)
Strategies – Case Study
ESA - APPRISE
ESAs
Prescriber Requirements
ETASU – Prescriber requirements
• Must complete ESA APPRISE Oncology
Program Training
• Enroll
E ll iin th
the ESA APPRISE O
Oncology
l
Program by submitting a completed ESA
APPRISE Oncology Program Enrollment
Form to the ESA APPRISE Oncology
Program Call Center
i. I have reviewed the current prescribing information for (ESAs).
http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM200104.pdf (Accessed 09/25/10)
ii. I understand that ESAs shortened overall survival and/or increased
the risk of tumor progression or recurrence in clinical studies in
patients with breast, non-small cell lung, head and neck, lymphoid
and cervical cancers
cancers.
iii. I understand that in order to decrease these risks, the lowest dose of
ESAs should be used to avoid red blood cell transfusion.
iv. I understand that ESAs are indicated for the treatment of anemia
due to the effect of concomitantly administered chemotherapy based
on studies that have shown a reduction in the need for red blood cell
transfusions in patients with metastatic, non-myeloid malignancies,
receiving chemotherapy.
http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM200104.pdf (Accessed 09/25/10)
ESAs
Prescriber Requirements
ESAs
Hospital Requirements
v. I understand that ESAs are not indicated for use in patients receiving
hormonal agents, therapeutic biologic products, or radiotherapy
unless receiving concomitant myelosuppressive chemotherapy.
Hospitals that dispense (ESAs) are certified through the hospital site
level enrollment in the ESA APPRISE Oncology Program.
vi. I understand that ESAs are not indicated for patients receiving
myelosuppressive therapy when the anticipated outcome is cure
cure.
To obtain site level enrollment as a hospital, the hospital designee
(e.g., pharmacy director, Head of Hematology/Oncology, or other
appointed designee) must complete and sign the ESA APPRISE
Oncology Program Enrollment Form for Hospitals
vii. I understand that ESA use has not been demonstrated in controlled
clinical trials to improve symptoms of anemia, quality of life, fatigue,
or patient well-being.
http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM200104.pdf (Accessed 09/25/10)
http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM200104.pdf (Accessed 09/25/10)
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ESAs
Hospital Requirements
ESAs
Hospital Requirements
I attest to the following on behalf of my hospital:
• I have completed the ESA APPRISE Oncology Program Training
Module.
• I understand that if healthcare providers in my hospital prescribe
(ESAs) to patients with cancer, failure of the staff to comply with
enrollment requirements will lead to suspension of access to (ESAs)
for my hospital.
• I will inform all (ESAs) prescribers at my hospital of the ESA
APPRISE Oncology Program training and oncology prescriber
certification requirements.
I will establish or oversee the establishment of a system, order sets,
protocols, or other measures designed to ensure that, in my hospital:
• (ESA) is only dispensed to patients with cancer after verifying:
– that the healthcare provider who prescribed (ESA) for patients
with cancer has enrolled in the ESA APPRISE Oncology
Program; and
– that the discussion between the patient and ESA APPRISE
Oncology Program-enrolled prescriber on the risks of (ESA)
therapy is documented by patient and prescriber signatures on
the ESA APPRISE Oncology Program Patient and Healthcare
Professional (HCP) Acknowledgement Form prior to initiation of
each new course of (ESA) therapy.
http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM200104.pdf (Accessed 09/25/10)
ESAs
Hospital Requirements
http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM200104.pdf (Accessed 09/25/10)
Strategies – Case Study
ESA - APPRISE
•
I am authorized to oversee compliance with program monitoring
and auditing to assess the effectiveness of the ESA APPRISE
Oncology Program.
• I will maintain evidence of compliance with the ESA APPRISE
Oncology Program for monitoring and auditing purposes, as follows:
– a list of each healthcare p
provider in my
y hospital
p
who p
prescribes
(ESA) for cancer patients
– documentation (i.e., unique enrollment ID number) that each
healthcare provider in my hospital who prescribes (ESA) for
patients with cancer is enrolled in the ESA APPRISE Oncology
Program
– documentation of the risk:benefit discussion between certified
prescriber and patient by archival storage of the ESA APPRISE
Oncology Program Patient and Healthcare Professional
Acknowledgment Form for each cancer patient for whom an
(ESA) prescription was filled
http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM200104.pdf (Accessed 09/25/10)
http://www.ashpadvantage.com/fdaaa (Accessed 09/25/10)
Strategies – Case Study
ESA - APPRISE
Strategies – Case Study
ESA - APPRISE
Process Flows
REMS – Required Elements
• Hospital Designee
• Hospital Enrollment
• Prescriber Enrollment
• Patient Education
• Patient and prescriber signature
• Documentation and Auditing
• Re-enrollment
Adult
Oncology
Group
Pediatric
Oncology
Group
Private
Physicians
Hospital
Oncology
Clinics
Private
Oncology
Clinics
Hospital
Inpatient
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Strategies – Case Study
ESA - APPRISE
Identify Stakeholders
•
•
•
•
•
Patient
Prescribers
Nursing
Pharmacy
Pharmaceutical
Company
•
•
•
•
•
•
•
Outpatient clinics
Private clinics
Private pharmacies
Medical records
IS
Risk management
Hospital legal
Strategies – Case Study
ESA - APPRISE
REMS – Required Elements
• Hospital Designee/Hospital Enrollment
– One designee for system or one per hospital
– Physician
Ph i i (M
(Medical
di l Di
Director
t off O
Oncology)
l
)
– Pharmacists
• Director of Pharmacy
• Pharmacy Manager
• Oncology Clinical Pharmacist, Drug Information
– Other
Consider one REMS “overseer”
Strategies – Case Study
ESA - APPRISE
Strategies – Case Study
ESA - APPRISE
REMS – Required Elements
• Prescriber Enrollment
REMS – Required Elements
• Patient Education
–
–
–
–
–
Employed physicians
P i t physicians
Private
h i i
Other prescribers
New practitioners
Credentialing process
– Required for all patients?
– Repeated?
R
t d?
Strategies – Case Study
ESA - APPRISE
Strategies – Case Study
ESA - APPRISE
REMS – Required Elements
• Patient and Prescriber signature
REMS – Required Elements
• Documentation and Auditing
– Initiated as outpatient
– Identification
Id tifi ti off appropriate
i t patient,
ti t iindication
di ti
• Order set
• CPOE
– Maintaining files
• Medical
M di l record
d
• Paper
• Electronic
– Verification prior to initiation of therapy
• Documentation
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Strategies – Case Study
ESA - APPRISE
Policies and Procedures
• Distribution of medication guides
• Patient enrollment, laboratory testing, and
monitoring
it i
• Communications and reporting
• Provider certification
• Dispensing and administration
• Documentation
Summary
• REMS – evolution of FDA safety programs
– FDAAA 2007
• Increased in black box warnings and other
safety communications
• Some overlap between legacy programs
and REMS
http://www.ashpadvantage.com/fdaaa (Accessed 09/25/10)
Summary
• Number of medications that have a
complex REMS program are likely to
increase
– Long acting opioids
• Hospital pharmacies will need to
implement new strategies to handle
complex REMS programs
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