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
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