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Financial Conflicts of Interest:
The Limits of Disclosure
and Management
Peter Lurie, MD, MPH
Public Citizen’s Health Research Group
Presented at:
Conflicts of Interest, Privacy/Confidentiality,
and Tissue Repositories:
Protections, Policies, and Practical Strategies
PRIM&R Conference
Boston, Massachusetts, May 3, 2004
Conflicts of Interest Affect …
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•
•
•
•
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Study design
Research ethics
Publication (or not)
Data presentation
Scientific debates
Regulatory Review
Placebo-controlled Trials of
Acyclovir to Suppress
Recurrent Herpes Genitalis
Percent Recurrence-free
100
90
Average acyclovir response in
1st 2 studies
80
70
60
Placebo
50
Acyclovir
40
30
Average placebo response
in 1st 2 studies
20
10
0
0
1
2
1984
3
4
5
1985
6
7
8
1986
9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
1988
89,91,92,94
Study Number and Year Published
1997
1998
A Drug Company-sponsored Unethical
Clinical Trial in Developing Countries
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•
•
•
Discovery Laboratories, Doylestown, PA
Synthetic surfactant (Surfaxin)
4 surfactants on the market (1st in 1990)
Associated with 34% relative reduction in
neonatal mortality (Cochrane metaanalysis)
“Without doubt the most thoroughly
studied new therapy in neonatal care”
(NEJM review)
A Drug Company-sponsored Unethical
Clinical Trial in Developing Countries
• Title of internal FDA meeting: “Use of
placebo-controls in life threatening
diseases: is the developing world the
answer?”
• Location: Mexico, Peru, Bolivia, Ecuador
• Design: Surfaxin vs. placebo (vs.
approved surfactant)
42 Randomized Trials of Natural and
Synthetic Surfactant in the Treatment of
Neonatal Respiratory Distress Syndrome
9
Number of trials
8
7
6
5
No Placebo
Placebo
4
3
2
1
0
1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000
Year of Publication
A Drug Company-sponsored Unethical
Clinical Trial in Developing Countries
• February 2001: Public Citizen writes to
HHS Secretary Tommy Thompson
• March 2001: Bolivian health ministry says
the study is “totally prohibited” for legal,
ethical and social reasons
• April 2001: Discovery announces study
changed to compare to known effective
surfactant
April 15, 1997
Content of Medical School-Industry
Multicenter Trial Contracts
Median Percentage of Contracts
12%
10%
10%
8%
6%
4%
2%
1%
0%
0%
Data collection and
monitoring
Source: NEJM 2002;3471335-41
All authors have
access to data
Trial results must be
published
Depiction of Alosetron (Lotronex)
Efficacy in Lancet
Source: Lancet 2000;355:1035-40
Public Citizen Depiction of Alosetron
(Lotronex) Efficacy
4.0
Mean Pain/Discomfort Score
3.5
3.0
2.5
1.97
Placebo
Alosetron
2.0
1.85
1.40
1.5
1.24
1.24
1.33
1.0
1.07
1.00
0.5
0.0
0
1
2
Month of Treatment
Source: Lancet 2000;356:2009
3
The Debate Over the Safety of
Calcium Channel Blockers
Financial Relationship with Sponsors
100%
90%
96%
80%
70%
60%
60%
50%
40%
37%
30%
20%
10%
0%
Support
Source: NEJM 1998;338:101-6
Neutral
Critical
FDA AC Member Recusals in
Drug Procuct-Specific Meetings
• 18 recusals (1.5%) in 81 meetings in study period
• Through January 2002: 7 recusals; 0% reason given
• After January 2002: 11 recusals; 36% reason given
• Examples of recusals:
 Research and consulting on topic of scientific meeting
 Principal investigator of related clinical trial
 Research on competing products and consulting on product
at issue
 Invention of competing product
Disclosed Conflict Rates for AC
Members and Consultants*
Through
January 2002
After
January 2002
Total
Per meeting COI
rate**
92%
87%
89%
Per person-meeting
COI rate***
24%
20%
22%
*Includes recusals
**Percentage of 81 meetings where at least 1 COI was disclosed
***Percentage of 1220 AC member or consultant person-meetings disclosing a COI
Value of Particular Conflict Types for
AC Members and Consultants,
January 1, 2001-June 30, 2003*
Consulting arrangements (n=114)
18%
Investments (n=78)
10%
4%
22%
No value given
33%
$0-5,000
$5,001-25,000
$25,001-50,000
$50,001-100,000
$0-10,000
$10,001-50,000
73%
41%
*Excludes 99 conflicts through January 2002 without any conflict-type details
Conclusions
• Conflict of interest permeates the entire
research process
• Financial conflict of interest, in particular,
has an adverse impact upon the public
face of science
• Some conflicts are so worrisome that
disclosure and “management” will not
suffice