Ethical Challenges Related to Financial Conflicts of Interest in Research

Jeremy Sugarman, MD, MPH, MABerman Bioethics Institute

Johns Hopkins University

Baltimore, Maryland USA

At the Newsstand “Safeguards Get Trampled in Rush for Research

Cash” Chicago Tribune, 9/5/99

“Senators Ask Drug Giant to Explain Grants to Doctors”

New York Times, 7/06/05 “How Tightly Do Ties Between Doctor and Drug

Company Bind” New York Times, 7/27/05

At the Bookstore Science in the Private Interest : Has the Lure of

Profits Corrupted Biomedical Research? Krimsky, 2003

The Truth About the Drug Companies: How They Deceive Us and What to Do About It

Angell, 2004

On The Take: How Medicine's Complicity with Big Business Can Endanger Your Health

Kassirer, 2004

At the Medical Library

“Handling conflicts of interest between industry and academia”

JAMA 2003; 3240-1

"Regulating academic-industrial research relationships--solving problems or stifling progress?"

NEJM 2005; 1060-5

"Reporting Conflicts of Interest, Financial Aspects of Research, and Role of Sponsors in Funded Studies"

JAMA 2005; 110-111

In the Beltway Institutional Review Boards: A Time for

Reform OIG, June 1998

Recruiting Human Subjects: Pressures in Industry-Sponsored Clinical Research

OIG, June 2000

Conflict of Interest Timeline

1999 Jesse Gelsinger dies in University of Pennsylvania trial

2000 HHS begins policy review Human Subject Protection and Financial Conflicts of Interest Conference HHS issues draft interim guidelines

2001 11 major medical journals require authors to disclose financial role of sponsor AAU issues report on financial conflicts AAMC issues guidelines for individual conflicts of interest

2002 NIH releases Review of Financial Conflict of Interest Policies of Grantee Institutions AAMC guidelines for institutional conflicts of interest

2004 HHS Final Guidance Document released

Ethical Foundations Scandals, codes, regulations and principles Fiduciary obligations Reservoir of trust

Fiduciary “a person holding the character of trustee, in

respect of the trust and confidence involved in it and scrupulous good faith and candor which it requires.”

a “person having duty, created by his undertaking, to act primarily for another’s benefit in matters connected with such understanding.”

Black’s Law Dictionary

Fiduciary Obligations Put aside self-interest Focus primarily on the interests of the person

for whom he or she serves as fiduciary Act to promote that individual’s interest and

so earn the trust of that individualMcCullough, et al 1998

Reservoir of Trust Individual physicians and investigators Specific institutions The research enterprise as a whole

Trust and Trustworthiness“Not all things that thrive when there is trust between people…are things that should be encouraged to thrive…There are immoral as well as moral trust relationships.”

Baier A, 1986

Spectrum of Conflicts Initial considerations Research design Prospective review In process

Recruitment Informed consent Integrity of the data

Reporting

Selected Types of Financial Interests Per capita payments Money received outside the study Investigator holds equity Institution holds equity

Potential Solutions Divest Minimize Disclose

Important Empirical Questions Regarding Disclosures of COI Who, What, When, Where, and How? How will these data be used? What are the effects on trust? What are the effects on the research

enterprise?

COINSConflict of Interest Notification Study Johns Hopkins

Jeremy Sugarman Duke

Kevin Weinfurt Rob Califf Kevin Schulman Joelle Friedman Jennifer Allsbrook Michaela Dinan

Wake Forest Mark Hall

NHLBI Grant: 1 R01 HL075538-01

COINS Overview

Institutional Policies

Officials/ Investigators

Potential Research Participants

Models for Disclosure

Effects of Disclosure

Policy Review Online and written policies of US academic medical

centers (AMCs) February-August, 2004 Identified materials for 98% of 123 AMCs

Weinfurt et al, Academic Medicine 2006; 81: 113-118.

Policy Review Online and written policies of US academic

medical centers (AMCs) February-August, 2004 Identified materials for 98% of 123 AMCs 48% mentioned disclosure to subjects as an

option 58% of those contained required or suggested

verbatim language Few suggested more than disclosure of sponsor

Weinfurt et al, Academic Medicine 2006; 81: 113-118.

The research[er] and/or [foundation]

may earn money from results of this

study.

Salary or compensation received for the %

effort invested for the performance of this

research project is not considered a conflict

and they need not be mentioned.

This study involves a conflict of interest

because the institution and/or (choose one)

the investigator will be compensated for

your participation in it. You should ask the

investigator how the institution and/or

(choose one) she (he) will benefit by your

participation in the study.

I have been informed that [a member of the study team]

has a personal financial interest in [the sponsor company

or other interests entity]. I have also been informed that

the nature of this financial interest and the design of the

study have been reviewed by the [institution’s] Conflict of

Interest Oversight Committee, and that this Committee

has determined that the investigator’s financial interest

would not compromise the quality or reliability of the study.

Furthermore, the [institution’s] Institutional Review Board

has determined that the investigator’s financial interest will

not aversely affect the subject’s welfare.

Interviews With Officials and Investigators Types of Institutions Sampled

Academic Medical Centers Independent Hospitals Independent IRBs Non- Affiliated Research Entities

Participation 23 IRB Chairs 14 COIC Chairs or similar official 7 investigators

Weinfurt et al, J Law Med Ethics 2006; 581-591.

Disclose the Amount of the Financial Interest?

“No!” according to investigators Complexity of the disclosure Amount “might detract from what really needs to be

decided” No consensus among officials

PRPs overestimate value and the power to influence Do not disclose amount

Investigators underestimate the power to influence, lay people do not Do disclose

We have not ever asked anyone to express the amount of money involved, really thinking that $1000 may be as bad as $20,000.

--IRB Chair

Describe Possible Implications of Financial Interest?

No, let them draw their own conclusions. Yes, warn them like we do on cigarette

ads. Difficult balance

I think that that is sort of leading the subject to where they might think that this is what is going to happen.

I think that if the relationship between the risk and the study was not clear, you might need to spell that out. But, to some degree I think you are just informing the subject. You are not trying to tell them what they should think about it.

--COIC Chair

PRP Focus Groups 16 groups (6-8 people each)

Healthy adults (6 Groups) Mildly/Chronically ill adults (6 Groups) Severely ill adults (2 Groups) Parents with healthy children (1 Group) Parents of children with illnesses (1 Group)

Stratified by race/ethnicity Conducted in New York, Chicago, and Durham,

NC

Weinfurt et al, J Gen Intern Med 2006; 21: 901-6.

PRPs on Disclosure and Trust Might decrease trust Might increase trust

Transparency Perception that financial interest is good

Need to maintain image of physician

Evolution of PRPs’ Thoughts

Few had considered financial interests and their implications in clinical research

Opportunity to ask questions during consent process Prior to focus group, would not have known what to

ask

COINS Overview

Institutional Policies

Officials/ Investigators

Potential Research Participants

Models for Disclosure

Effects of Disclosure

Models for Disclosure Expert Panel

Mark Barnes, JD, LLM (Ropes & Gray), Becky Coleman, PharmD (Theravance, Inc.), Joseph DiCesare, MPH, RPh (Novartis Pharmaceuticals Corporation), John M. Falletta, MD (Duke University Medical Center), Robert Gatter, JD, MA (Penn State University), Julie Gottlieb, MA (Johns Hopkins University), Jeffrey Kahn, PhD, MPH (University of Minnesota), Mary Faith Marshall, Ph.D. (University of Minnesota), S. Van McCrary, Ph.D., J.D., M.P.H. (State University of New York at Stony Brook), Erica Rose, JD (GlaxoSmithKline), Michael B. Waitzkin, JD (FoxKiser)

Focus Groups Cognitive Pre-testing

Weinfurt, et al. IRB 2007; 29:1-5

COINS Overview

Institutional Policies

Officials/ Investigators

Potential Research Participants

Models for Disclosure

Effects of Disclosure

Assessing Effects of Disclosure Online survey of 3,520 participants

Diabetics and asthmatics Hypothetical clinical trial 1 of 5 financial interests disclosed

Per capita payments Money received outside the study Investigator holds equity Institution holds equity Generic

0

10

20

30

40

50

60

70

I definitelywould notparticipate

I probablywould notparticipate

I am uncertainif I would orwould notparticipate

I probablywould

participate

I definitelywould

participate

Per

cen

t o

f R

esp

on

den

ts

Willingness to Participate

0

10

20

30

40

50

60

70

Greatlyincreased

Increased Neitherincreased ordecreased

Decreased Greatlydecreased

Per

cen

t o

f R

esp

on

den

ts

Change in Trust Due to Disclosure

0

10

20

30

40

50

60

70

Do notunderstand at

all

Understand alittle

Understandwell

Understandvery well

Understandcompletely

Pe

rce

nt

of

Re

sp

on

de

nts

Self-Rated Understanding of Disclosed Financial Benefit

0

10

20

30

40

50

60

70

Not at allsurprised

Somewhatsurprised

Surprised Very surprised Extremelysurprised

Per

cen

t o

f R

esp

on

den

ts

Surprise Over Disclosed Information

0

10

20

30

40

50

60

70

Greatlydecrease quality

Somewhatdecrease quality

Quality willneither increasenor decrease.

Somewhatincrease quality

Greatly increasequality

Per

cen

t o

f R

esp

on

den

ts

Perceived Effect on Scientific Quality

Does the Type of Interest Matter?

Greater concern over investigator holding equity compared to per capita payment

Other types of financial interest did not differ substantially in their effects on participants

Before leaving it up to the PRP to assess risk . . .

Understanding of implications Some feel financial interest increases chance that

investigators are committed, ethical, and confident that the experimental therapy will work

Invitation to ask questions during consent process People might not know what to ask

With greater medical risk, some people may not pay attention to financial disclosure, but it is still important to them.

The Process of Disclosure Study of 300 clinical research coordinators to

understand their role in disclosing financial interests in research, and possible barriers to such disclosures

Survey domains Awareness of financial interests in research Experience and comfort with disclosure of such interests Barriers to disclosure

Results Experience

41% reported disclosing financial interests to PRPs 28% reported being asked about financial interests

28% somewhat or not at all comfortable with answering questions about financial interests

Barriers Lack of information PRPs wont understand Investigator privacy

Suggestions More education and training would facilitate the

disclosure of financial interests in research to PRPs during the informed consent process

Failure to provide such training could result in discomfort that might discourage the effective communication of financial disclosures in research to PRPs

Next Steps Vignette study with patients with coronary artery disease

Provided with a copy of an informed consent document for a hypothetical trial

Three disclosure arms (per capita, equity, none) Telephone review to simulate the informed consent

process Survey regarding willingness to participate, trust, etc

Conflict of interest management study Determine how and when disclosure is selected as a

management strategy