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Financial Conflicts of Interest in Research Marion Danis, M.D. Department of Clinical Bioethics National Institutes of Health Washington, DC.

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Presentation on theme: "Financial Conflicts of Interest in Research Marion Danis, M.D. Department of Clinical Bioethics National Institutes of Health Washington, DC."— Presentation transcript:

1 Financial Conflicts of Interest in Research Marion Danis, M.D. Department of Clinical Bioethics National Institutes of Health Washington, DC

2 DISCLAIMER The views expressed in this presentation do not represent the views of the NIH, DHHS, or any other government agency or official.

3 Outline  Background The Problem with Conflicts of Interest  Definition What is Conflict of Interest?  Data  Analysis and recommendations for managing COI For individual investigators For institutions and institutional officers

4 Does Conflict Influence You?  Would you present data differently in a lecture if a drug company were paying you R$15,000 to give the lecture?  Would you persist in conduct of a study with adverse outcomes if a company were funding your research?

5 What is a Conflict of Interest?  A conflict of interest occurs when a secondary interest distorts or has the potential to distort a judgment related to a primary interest  A professional’s judgment does not necessarily have to be biased in order for that researcher to have a conflict of interest — even the appearance of a conflict of interest is ethically worrisome

6 Primary Interests  Professionals have a primary interest—the goal of their profession For researchers:  Producing generalizable knowledge  Ensuring the safety of research subjects  Disseminating research results

7 Secondary Interests  Professional goals Publishing Obtaining future research funding Gaining recognition and fame  Personal goals Spending time with his/her family Earning a good income Other personal interests such as religion, traveling, social activities, etc. Political activism

8 Bad Outcomes Associated with Conflict of Interest  Recent deaths have raised the question of whether researchers were more concerned about financial matters than patient safety Gelsinger case at University of Pennsylvania Fred Hutchinson Cancer Center

9 Research Funding in the United States Phase I-III Trials: -PharmaceuticalsR$65 billion -NIHR$20 billion Industry has dramatically increased its funding of clinical research compared to the government 32% 62%

10 Assessing Secondary Interests  It is important to note that secondary interests on their own are not bad or unethical  Usually these secondary interests are good and often praiseworthy Time devoted to one’s family Lobbying for a political belief Volunteering for a local charity

11 Assessing Secondary Interests  What makes secondary interests problematic?  Their ability to unduly influence decisions about an individual’s primary interest  The key ethical issue is the relationship between a primary and a secondary interest

12 Focus on Financial Conflicts of Interest Why this focus?  Money is… Multi-purposed A key motivating factor Can be quantified Relatively easy to regulate Source of public mistrust

13 Frequency of Financial Interests  In a survey of published randomized controlled trials, of authors that disclosed a financial interest… 30% Employment 22% Consultancies and Honoraria 18% Grants 7% Educational/Speaker’s Bureau 7% Stock ownership 5% Advisory Board 1% Patents/Licenses Gross et al. JAMA 2003

14 Possible Threats Posed by Researchers’ Conflicts of Interest Valid research design Data integrity Dissemination of results Research subject safety

15 Research Design  Industry-sponsored research was more likely to be double blind and to report adverse events in the experimental groups than research sponsored by non- profits Liebeskind et al. BMJ 1999

16 Data Collection Do financial interests compromise data collection and interpretation?  Data suggest that industry funded clinical research leads to positive results more frequently than non-industry funded research

17 Data Collection  Of 11 meta-analyses, 9 reported that industry sponsored trials were significantly more likely to yield pro- industry results  Odds ratio of having industry sponsorship and pro-industry conclusion: OR=3.60 (2.63-4.91) Bekelman et al. JAMA 2003

18 Data Collection Possible explanations: Industry commits resources only to clinical research that is likely to yield positive results Industry terminates large randomized studies early that are likely to have side effects and less likely to be successful or to generate huge profits

19 Dissemination of Results  Industry-funded clinical research studies that produce positive results are more likely to be published compared to government-funded clinical research

20 Dissemination of Results  Meta-analysis of data from randomized trials that evaluated an SSRI against placebo in the treatment of depression in children Articles reviewed were published in a peer- reviewed journal or unpublished (and reviewed by the Committee on Safety of Medicines) Whittington et al. Lancet 2004

21 Dissemination of Results  Results: When published data alone were considered, it appeared that there was a favorable risk-benefit profile for 5/5 drugs studied Addition of unpublished data indicated that the risks outweigh the benefits for 4/5 drugs studied  Unknown if unpublished articles were not published due to publication bias against negative studies at major journals or the result of industry withholding negative data Whittington et al. Lancet 2004

22 Patient Safety  No data  No data on overall safety of clinical research

23 Patient Safety  No data on overall safety of clinical research  In a bone marrow protocol at Fred Hutchinson Cancer Research Center, 80/82 enrolled research subjects died  Study investigators had R$937 million of holdings in a drug company sponsoring part of the research

24 Patient Safety  This does not necessarily indicate that a conflict of interest impacted researchers’ judgment or patient safety  Need to be sure we do not draw unsubstantiated conclusions from the data  Raises questions and concerns, but deaths are not necessarily due to the presence of conflicts of interest

25 Summary of Relationship of FCI and Researchers’ Behavior  Researcher financial interests are common: 25% to 33% of researchers  Financial interests Do appear to influence researcher judgment and data dissemination Do not appear to influence research design Influence data collection and interpretation ? Influence patient safety ?

26 Protection against COI  Aim to reduce: Likelihood of harm: Limit the possibility of a harm occurring in the first place Magnitude of harm: Lessen the negative consequences of the harm

27 Protections for Individual Investigators  Disclosure To institution/IRB/COI committee To patients In journals  Management Data safety and monitoring boards (DSMBs) Independent consent monitors  Restrictions/Prohibitions Recusal Divestment Resignation Policies prohibiting types/amounts of financial interests  Creation of trial registries

28 Problems with Protections  No consistent standards for disclosure: 2001 US Government Accounting Office study of 5 major research institutions in the US Rules regarding disclosure and prohibitions of financial interests varied widely Limits of financial interests varied from R$30,000 to R$300,000

29 Problems with Protections  No consistent standards for disclosure:  Disclosed information is not well recorded and not readily available to the IRBs  Researchers are not aware or well-informed of disclosure policies At UCSF and Stanford, 58% of researchers could not accurately describe the COI policy of their institution

30 Institutional Conflict of Interest  “An institution may have a conflict of interest in human subjects research whenever the financial interest of the institution, or of an institutional official acting within his authority, might affect - or reasonably appear to affect - institutional processes for the conduct, review, or oversight or human subjects research.”  AAMC Task Force 2002 Report

31 Concerns relating to Institutional COI  The agenda of a sponsoring agency may conflict with the agenda of the university  Commercial interests of a sponsor may conflict with social goals of scientific research  If the institution aligns itself with the sponsor the institution’s interests can conflict with goals of science and protection of human subjects

32 Concerns relating to Institutional COI  The goals of the sponsor may inappropriately affect the research environment Sponsors seek a positive outcome from the research at an acceptable cost Sponsors seek to protect intellectual property related to the subject matter of the research

33 How Institutions Benefit from Sponsored Research  Overhead payments  Compensation for enrolling subjects  Stock options  Royalties from sale or license of patented technologies  Partnerships with industry  Donations or grants from industry

34 Conflicts of Institutional Officials  Leaders: deans, department heads, trustees, officers who make institutional decisions are charged with making these decisions in the institution’s interest  Personal interests and financial holdings may give rise to conflicts with institutional responsibilities  Institutional leaders are sometimes given appointments to start up companies

35 Conflicts of Institutional Officials  Institutional Review Boards members who review proposed research may have ties to industry: Own stock Receive royalties Participate in clinical trials Receive industry support for their research

36 Conflicted IRB Officials  Decisions about research may be improperly influenced  Encouragement or permission for research that may not meet requirements for human subjects protection  Allocation of institutional resources such as funding, personnel, equipment, space to commercial sponsor’s research

37 Threats to Trainees  Encouragement of trainees to pursue research that is not in the trainee’s educational interest  Involvement of trainees in research that cannot be freely published

38 Threats to Human Subjects Protection  Pressure to recruit inappropriate subjects to yield large study sample quickly  Due to sponsor’s interest in completing trials quickly to gain time on exclusive patent holdings

39 Threats to Human Research Subjects from Institutional COI  Imperative to recruit quickly and show positive results may prompt: Subtle pressure to misrepresent the misrepresent the true nature of the trial Failure to describe alternatives to trial participation Insufficient caution in assessing the capacity of a research subject to consent Inclusion of subjects who do not meet enrollment criteria Failure to monitor precisely and report adverse events

40 Threats to Research Integrity  Sponsored research is more likely to report favorable outcomes Trial design may favor positive outcome Publication of negative results may be delayed or restricted

41 Protections against Institutional COI  Institutions should establish administrative processes to assess and manage conflict  Cooperation between institutions and sponsors should be at a distance

42 Protections against Institutional COI  Disclosure policies Who should disclose What should be disclosed To whom to disclose  IRB  Research subjects  Publications

43 Protections against Institutional COI  Assignment of oversight responsibility Institutional conflict of interest committee  Members with experience, seniority, independence  Outside the line of authority for overseeing institutional research  Community representation  Independent review of research Study design, data analysis, publication  Independent investment management

44 Protection for Institutional Officers  Required disclosure of conflict of interest  Divestiture of investment  Prohibition of research by persons who have combined roles as official and scientist

45 Protections for IRBs and IRB Members  Fund IRB from some other portfolio than that of the Dean of Research  Require IRB members to disclose personal finances  Have IRB review clinical trial agreements to avoid publication restrictions  Conduct educational programs on COI as requirement for IRB members

46 Conclusions  The opportunity to participate in research creates important obligations for individual investigators and their institutions to conduct research with integrity  Personal responsibility must be combined with institutional structures to address the conflicts of interest that inevitably arise in carrying out research.

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