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