Financial Conflicts of Interest: The Limits of Disclosure and Management Peter Lurie, MD, MPH Public...
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Transcript of Financial Conflicts of Interest: The Limits of Disclosure and Management Peter Lurie, MD, MPH Public...
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 …
• Study design
• Research ethics
• Publication (or not)
• Data presentation
• Scientific debates
• Regulatory Review
Placebo-controlled Trials of Acyclovir to Suppress
Recurrent Herpes Genitalis
0
10
20
30
40
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Study Number and Year Published
Perc
ent R
ecur
renc
e-fre
e
Placebo
Acyclovir
Average acyclovir response in 1st 2 studies
Average placebo response in 1st 2 studies
1984 1985 1986 1988 89,91,92,94 1997 1998
A Drug Company-sponsored Unethical Clinical Trial in Developing Countries
• Discovery Laboratories, Doylestown, PA• Synthetic surfactant (Surfaxin)• 4 surfactants on the market (1st in 1990)• Associated with 34% relative reduction in
neonatal mortality (Cochrane meta-analysis)“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
0
1
2
3
4
5
6
7
8
9
1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000
Year of Publication
Num
ber
of tr
ials
No Placebo
Placebo
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
10%
1%
0%0%
2%
4%
6%
8%
10%
12%
Data collection andmonitoring
All authors haveaccess to data
Trial results must bepublished
Med
ian
Per
cen
tag
e o
f C
on
trac
ts
Source: NEJM 2002;3471335-41
Depiction of Alosetron (Lotronex) Efficacy in Lancet
Source: Lancet 2000;355:1035-40
Public Citizen Depiction of Alosetron (Lotronex) Efficacy
1.97
1.401.24 1.24
1.85
1.33
1.07 1.00
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
0 1 2 3
Month of Treatment
Mea
n P
ain
/Dis
com
fort
Sco
re
Placebo
Alosetron
Source: Lancet 2000;356:2009
The Debate Over the Safety of Calcium Channel Blockers
60%
37%
96%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Support Neutral Critical
Fin
anci
al R
elat
ion
ship
wit
h S
po
nso
rs
Source: NEJM 1998;338:101-6
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*
*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
Through January 2002
After January 2002
Total
Per meeting COI rate** 92% 87% 89%
Per person-meeting COI rate*** 24% 20% 22%
Value of Particular Conflict Types for AC Members and Consultants,
January 1, 2001-June 30, 2003*
Consulting arrangements (n=114)
10%
73%
18%
No value given
$0-10,000
$10,001-50,000
*Excludes 99 conflicts through January 2002 without any conflict-type details
22%
41%
33%
4%
$0-5,000
$5,001-25,000$25,001-50,000
$50,001-100,000
Investments (n=78)
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