Is it Really All about the Money? Reconsidering Non-Financial Interests in Medical Research

Department of Health and Human Services, “Responsibility of Applicants for Promoting Objectivity in Research for Which Public Health Service Funding Is Sought and Responsible Prospective Contractors,” 76 Federal Register 53256 (August 25, 2011).

Id., at 53258.

Institute of Medicine, Conflict of Interest in Medical Research, Education, and Practice (Washington, D.C.: National Academies Press, 2009) (hereinafter cited as IOM, Conflict of Interest Report).

See, e.g., Washington University School of Medicine Conflicts of Interest Policy Part I, §B.3, Part II, §D.1 (while the University's conflict of interest policy acknowledges that faculty and staff face many forms of competing interests, the Disclosure Review Committee addresses only financial conflicts), available at <http://medcoi.wustl.edu/medadmin/coisite.nsf/0ee53e934810efcd86256a94005e5f7d/1da8f38a49d1966786256c0d0055337e?OpenDocument>(last visited July 24, 2012);

Mayo Clinic Conflict of Interest Policy §§I, II (recognizing that “conflict of interest” encompasses financial or other personal considerations but then defining conflicts of interest for purposes of institutional policy as situations where there may have been influence by “significant financial conflict of interest”), available at <https://secure.ethicspoint.com/domain/media/en/gui/23071/mcConfict_of_Interest_Policypdf>(last visited July 24, 2012);

Report of the AAMC-AAU Advisory Committee on Financial Conflicts of Interest in Human Subjects Research, Protecting Patients, Preserving Integrity, Advancing Health: Accelerating the Implementation of COI Policies in Human Subjects Research (2008) (concentrating exclusively on financial conflicts);

Blum J. A. , “Requirements and Definitions in Conflict of Interest Policies of Medical Journals,” JAMA 302, no. 20 (2009): 2230–2234 (most medical journals surveyed requested author disclosure of financial conflicts but only a minority requested disclosure of other potential conflicts such as personal relationships).

The IRB regulations restrict IRB members with conflicting interests from participating in protocol reviews, but the rules do not specify what types of interests trigger the restrictions. See 45 C.F.R. §46.107(e); 21 C.F.R. § 56.107 (e). IRBs apply the rules more often to financial conflicts than non-financial interests. See Wolf L.E. , “Conflicts of Interest in Research: How IRBs Address Their Own Conflicts,” IRB: Ethics and Human Research 29, no. 1 (2007): 6–12 (70% of surveyed IRBs interpret conflict of interest for an IRB member as covering financial ties, but only 52% consider some relationships with study personnel to be a conflict). Among IRBs that consider non-financial ties, not all potentially conflicting relationships are consistently included.

Id.

See Brody H. , “Clarifying Conflict of Interest,” American Journal of Bioethics 11, no. 1 (2011): 23–28.

See generally “Following the Money,” American Journal of Law and Medicine 36 (2010): 288–481 (symposium issue addressing the core theme of following the money in health care).

See Shepherd L. , “In Plain Sight: A Simple Solution to a Fundamental Challenge in Human Research,” Journal of Law, Medicine and Ethics (forthcoming 2012);

IOM, Conflict of Interest Report, supra note 3, at 97.

See DuVal G. , “Institutional Conflicts of Interest: Protecting Human Subjects, Scientific Integrity, and Institutional Accountability,” Journal of Law, Medicine & Ethics 32, no. 4 (2004): 613–625.

Sollitto S. , “Intrinsic Conflicts of Interest in Clinical Research: A Need for Disclosure,” Kennedy Institute of Ethics Journal 13, no. 2 (2003): 83–91.

Kassirer J. P. , “Financial Conflicts of Interest in Biomedical Research,” New England Journal of Medicine 329, no. 8 (1993): 570–571.

See Sage W. , “Some Principles Require Principals: Why Banning ‘Conflicts of Interest’ Won't Solve Incentive Problems in Biomedical Research,” Texas Law Review 85 (2007): 1413–1463.

See Fry-Revere S. , “More Regulation of Industry Supported Biomedical Research: Are We Asking the Right Questions?” Journal of Law, Medicine & Ethics 37, no. 3 (2009): 420–430 (2009).

Levinsky N. G. , “Nonfinancial Conflicts of Interest in Research,” New England. Journal of Medicine 347, no. 10 (2002): 759–761.

Harrington P. J. , “Faculty Conflicts of Interest in an Age of Academic Entrepreneurialism: An Analysis of the Problem, the Law and Selected University Policies,” Journal of College and University Law 27, no. 4 (2001): 775–831.

The PLoS Medicine Editors, “Making Sense of Non-Financial Competing Interests,” PLoS Medicine 5, no. 9 (2008): 1299–1301;

International Committee of Medical Journal Editors, Uniform Requirements for Manuscripts Submitted to Biomedical Journals: Ethical Considerations in the Conduct and Reporting of Research: Conflicts of Interest, available at <http://www.icmje.org/ethical_4conflicts.html>(last visited July 24, 2012).

See Sollitto, supra note 10.

Wolf L. E. , “Ethical Issues in Clinical Research: An Issue for All Internists,” American Journal of Medicine 109, no. 1 (2000): 82–85.

Cope M. B. , “White Hat Bias: A Threat To The Integrity of Scientific Reporting,” Acta Paediatrica 99, no. 11 (2010): 1615–1617.

Korn D. , “Conflicts of interest in Biomedical Research,” JAMA 284, no. 17 (2000): 2234–2237.

See Kuszler P. C. , “Curing Conflicts of Interest in Clinical Research: Impossible Dreams and Harsh Realities,” Widener Law Symposium Journal 8 (2001): 115–152;

Institute of Medicine, Responsible Research: A Systems Approach to Protecting Research Participants (Washington, D.C.: The National Academies Press, 2002) (hereinafter cited as IOM, Responsible Research): At 187.

See Levinsky, supra note 13, at 760.

In the federally sponsored Tuskegee Syphilis Study, poor African-American men suffering from syphilis were deliberately left untreated as part of an investigation of the natural history of the disease. The subjects were not aware that they were in the study and several were not even told that they had syphilis. See generally Jones J. , Bad Blood: The Tuskegee Syphilis Experiment – A Tragedy of Race and Medicine (New York: The Free Press, 1981).

Live cancer cells were injected into elderly patients at the Jewish Chronic Disease Hospital in Brooklyn without the patients' knowledge or consent. The study, funded in part by the United States Public Health Service and American Cancer Society, investigated how a weakened immune system influenced the spread of cancer. See Hyman v. Jewish Chronic Disease Hospital, 251 N.Y.S.2d 818 (N.Y. App. Div. 1964);

Rice T. W. , “The Historical, Ethical, and Legal Background of Human Subjects Research,” Respiratory Care 53, no. 10 (2008): 1325–1329.

National Research Act of 1974, Pub. L. No. 93–348 (1974), 88 Stat. 342.

The Act required that institutions receiving Department of Health, Education, and Welfare funding for research studies establish institutional review boards in order to protect subjects. It also authorized creation of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. Id.

In 1981, the Department of Health and Human Services (HHS) and the Food and Drug Administration (FDA) substantially revised their regulations, implementing various provisions of the National Research Act of 1974, see id., and recommendations of the Belmont Report issued by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. See National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research (1978). The 1981 research rules have remained largely unchanged to present day, although HHS and FDA are considering more comprehensive changes to the regulations. See Department of Health and Human Services and the Food and Drug Administration, “Human Subjects Research Protections: Enhancing Protections for Research Subjects and Reducing Burden, Delay, and Ambiguity for Investigators,” 76 Federal Register 44512 (July 26, 2011) (Advanced notice of proposed rulemaking).

See IOM, Responsible Research, supra note 18, at 117.

See also Ossorio P. N. , “Pills, Bills, and Shills: Physician-Researcher's Conflicts of Interest,” Widener Law Symposium Journal 8, no.1 (2001): 75–103.

See Landon M. B. , “A Multicenter, Randomized Trial of Treatment for Mild Gestational Diabetes,” New England Journal of Medicine. 361, no. 14 (2009): 1339–1348.

Stell L. K. , “Conflict of Interest in Diabetes Research,” Journal of Diabetes 2, no. 1 (2010): 5–6, at 5 (“imagine the outcry were similar excess harm to an at-risk population of pregnant women and infants allowed to accumulate in an industry-sponsored trial where its physician-investigators held equity interests in the outcome.”).

See Werth B. , “The Drug That Works in Pittsburgh,” New York Times, September 30, 1990.

See generally World Health Organization, Evidence on The Long-Term Effects of Breastfeeding: Systematic Reviews and Meta-Analyses (WHO Press, Geneva: 2007);

Atkinson R. L. , “White Hat Bias: The Need for Authors to Have the Spin Stop with Them,” International Journal of Obesity 34, no. 1 (2010): 83.

See Cope, supra note 16, at 1616.

See Kjaergard L. L. , “Association Between Competing Interests and Authors' Conclusions: Epidemiological Study of Randomised Clinical Trials Published in the BMJ,” British Medical Journal 325, no. 7358 (2002): 1–4.

See Luborsky L. , “The Researcher's Own Therapy Allegiances: A ‘Wild Card’ In Comparisons of Treatment Efficacy,” Clinical Psychology: Science and Practice 6, no. 1 (1999): 95–106.

Maj M. , “Non-Financial Conflicts of Interest in Psychiatric Research and Practice,” The British Journal of Psychiatry 193, no. 2(2008): 91–92;

The PLoS Medicine Editors, supra note 14.

See infra notes 44 to 47 and accompanying text.

Menikoff J. Richards E. , What the Doctor Didn't Say: The Hidden Truth about Medical Research (New York: Oxford University Press, 2006): At 226.

The PLoS Medicine Editors, supra note 14, at 1299.

See Korn, supra note 17, at 2234.

Sharmon Sollitto and colleagues assert that “intrinsic Conflicts of interest pose as grave a problem as overt personal financial conflicts.” Sollitto , supra note 10, at 85 (2003).

See also Horrobin D.F. , “Non-Financial Conflicts Are More Serious Than Financial Conflicts,” British Medical Journal 318, no.7181 (1999): 466 (“non-financial Conflicts are much more serious barriers to the fair conduct, reporting, and criticism of research studies.”).

See IOM, Conflict of Interest Report, supra note 3, at 47.

See Guyatt G. , “The Vexing Problem of Guidelines and Conflict of Interest: A Potential Solution,” Annals Internal Medicine 152, no. 11 (2010): 738–741.

Id.

Tsai A. C. , “Managing Nonfinancial Conflicts of Interest: How the New McCarthyism Could Work,” American Journal of Bioethics 11, no. 1 (2011): 42–44, at 42–43.

Boyd E. A. , “Defining Financial Conflicts and Managing Research Relationships: An Analysis of University Conflict of Interest Committee Decisions,” Science and Engineering Ethics 13, no. 4 (2007): 415–435.

Huddle T. S. , “Clarifying the Dispute over Academic-Industry Relationships,” American Journal of Bioethics 11, no. 1 (2011): 47–49.

Horton R. , “Conflicts of Interest in Clinical Research: Opprobrium or Obsession?” The Lancet 349, no. 9059 (1997): 1112–1113.

See notes 30 to 32 supra and accompanying text.

See Robertson C. , “Effect of Financial Relationships on the Behaviors of Health Care Professionals: A Review of the Evidence,” Journal of Law, Medicine & Ethics 40, no. 3 (2012): 502–516.

Warner T. D. , “What Do We Really Know about Conflicts of Interest in Biomedical Research?” Psychopharmacology 171, no. 1 (2003): 36–46.

Bailey R. , Scrutinzing Industry-Funded Science: The Crusade against Conflicts of Interest (New York: American Council on Science and Health, 2008), available at <http://fbae.org/2009/FBAE/website/images/PDF%20files/ACSH-Scrutinizing%20Industry%20Science.pdf>(last visited August 19, 2012).

Stossel T. P. , “Regulating Academic-Industrial Research Relationships – Solving Problems or Stifling Progress?” New England Journal of Medicine 353, no. 10 (2005): 1060–1065.

See Johnston J. , “Financial Conflicts of Interest in Biomedical Research,” in Trust and Integrity in Biomedical Research (The Johns Hopkins University Press, Baltimore: 2010): At 16. As even the IOM 2009 Conflict of Interest Report concedes, “on many topics related to Conflicts of interest, no systematic studies are available… [while] for other topics, data are suggestive rather than definitive.”

IOM, Conflict of Interest Report, supra note 3, at 4.

See IOM Conflict of Interest Report, supra note 3, at 25.

Remarks of Marcia Angell, HHS Conference on Financial Conflicts of Interest, August 16, 2000, available at <http://www.hhs.gov/ohrp/archive/coi/angell.htm>(last visitedJuly 24, 2012).

See Sollitto , supra note 10, at 85.

Kachuck N. J. , “Managing Conflicts of Interest and Commitment: Academic Medicine and the Physician's Progress,” Journal of Medical Ethics 37, no. 1 (2011): 2–5, at 4.

See Ossorio, supra note 24, at 99.

See id.

See Menikoff, supra note 33, at 226.

Nelson D. K. , “Conflict of Interest: Researchers,” in Amdur R. Bankert E. , Institutional Review Board: Management and Function (Sudbury, MA: Jones and Bartlett Publishers, 2002): 197–203, at 198.

See Stossel, supra note 46.

See IOM Conflict of Interest Report, supra note 3, at 47.

See Part IV infra.

See supra notes 24 to 33 and accompanying text.

See Nelson, supra note 55, at 198.

See Korn, supra note 17, at 2234.

See supra notes 24 to 33 and accompanying text.

See The Center for Health and Pharmaceutical Law and Policy, Seton Hall University School of Law, The Limits of Disclosure as a Response to Financial Conflicts of Interest in Clinical Research (2010), available at <http://law/shu.edu/Programs-Centers/HealthTechIP/HealthCenter/upload/health-center-whitepaper-dec2010.pdf>.

Department of Health and Human Services, Responsibility of Applicants for Promoting Objectivity in Research for which Public Health Service Funding is Sought and Responsible Prospective Contractors, 76 Federal Register 53256, 53258 (August 25, 2011) (implementing final rule). HHS also justified the exclusive focus on financial ties because the authorizing legislation for the regulations expressly references financial conflicts.

Id. See also 42 U.S.C. § 289b-1.

See, e.g., Brennan T. A. , “Health Industry Practices That Create Conflicts of Interest,” JAMA 295, no. 4 (2006): 429–433.

Dana J. , “How Psychological Research Can Inform Policies for Dealing with Conflicts of Interest in Medicine,” in IOM Conflict of Interest Report, Appendix D, supra note 3, at 370.

See, e.g., Katz D. , “All Gifts Large and Small: Toward an Understanding of the Ethics of Pharmaceutical Industry Gift-Giving,” American Journal of Bioethics 3, no. 3 (2003): 39–46;

Association of American Medical Colleges et al., The Scientific Basis of Influence and Reciprocity: A Symposium (Washington, D.C.: 2007), available at <https://www.aamc.org/download/157014/data/new_document.pdf>(last visited August 10, 2012).

Dana J. , “A Social Science Perspective on Gifts to Physicians From Industry,” JAMA 290, no. 2 (2003): 252–255.

Magnus S. A. , “Physicians' Financial Incentives in Five Dimensions: A Conceptual Framework for HMO Managers,” Health Care Management Review 24, no. 1 (1999): 57–72.

Saver R. S. , “Squandering the Gain; Gainsharing and the Continuing Dilemma of Physician Financial Incentives,” Northwestern University Law Review 98, no. 1 (2003): 145–238.

See Magnus, supra note 67.

Saver, supra note 67, at 191–194.

See Magnus, supra note 67, at 67.

Fry-Revere S. , “More Regulation of Industry Supported Biomedical Research: Are We Asking the Right Questions?” Journal of Law, Medicine & Ethics 37, no. 3 (2009): 420–430.

See, e.g., Bailey R. , “Ties that Bind: The Canonical Conflict of Interest Cases,” Reason, October 2007, available at <http://reason.com/archives/2007/10/01/ties-that-bind>(last visited July 24, 2012) (“One of the often-expressed concerns about Conflicts of interest is that greedy researchers will harm subjects and patients as they rush treatments to market. [The Gelsinger] case stands out in this respect.”).

See Stolberg S. G. , “The Biotech Death of Jesse Gelsinger,” New York Times Magazine, November 28, 1999, at 136.

Goldner J. A. , “Dealing with Conflicts of Interest in Biomedical Research: IRB Oversight as the Next Best Solution to the Abolitionist Approach,” Journal of Law, Medicine & Ethics 28, no. 4 (2000): 379–404.

See Menikoff , supra note 33, at 224.

Wilson R. F. , “Estate of Gelsinger v. Trustees of University of Pennsylvania: Money, Prestige, and Conflicts of Interest in Human Subjects Research,” in Johnson S. , eds., Health Law and Bioethics: Cases in Context (New York: Aspen Publishers, 2009): At 229–231.

See Alvino L. A. , “Who's Watching the Watchdogs? Responding to the Erosion of Research Ethics by Enforcing Promises,” Columbia Law Review 103 (2003): 893–923, at 902 note 67 (“Although the news stories written immediately after Jesse Gelsinger's death portrayed the experiment as a noble endeavor with a tragic outcome, that tone was soon replaced with one of anger and general distrust of the medical research community, as evidence of apparent financial conflicts of interest and breaches of protocol eventually emerged.”).

Nelson D. Weiss R. , “Hasty Decision in the Race to a Cure? Gene Therapy Study Proceeded Despite Safety, Ethics Concerns,” Washington Post, November 21, 1999.

Wilson J. M. , “Lessons Learned From the Gene Therapy Trial For Ornithine Transcarbamylase Deficiency,” Molecular Genetics and Metabolism 96, no. 4 (2009): 151–157.

Id., at 155.

See Menikoff , supra note 33, at 226;.

Wolf, supra note 16, at 84.

Wilson , supra note 73, at 251.

See Menikoff , supra note 33, at 227 (“[I]t seems unlikely that administrators at one of the nation's most prestigious institutions, who regularly deal with amounts in the many millions of dollars, would have been pressuring researchers to cut corners because of the possibility that Penn's rather modest share of the company ($1.4 million) would then be worth more.”).

Steinbrook R. , “The Gelsinger Case,” in the Oxford Textbook of Clinical Research Ethics (Oxford: New York, 2008): 110–120, at 118.

See also Menikoff , supra note 33, at 226 (“There is little reason to think that financial interests had anything to do with the specific ‘wrong things’ that were considered to have taken place in the study.”).

See Steinbrook, supra note 81, at 116.

Department of Health and Human Services, Financial Relationships and Interests in Research involving Human Subjects: Guidance for Human Subject Protection, 69 Federal Register 26393 (2004).

See Steinbrook, supra note 81, at 118.

See supra notes 65 to 66 and accompanying text.

See, e.g., Cialdini R. B. , Influence: The Psychology of Persuasion, 2nd ed. (New York: Quill, 1993): At 18.

Id.

See, e.g., Katz , supra note 66.

Blumenthal D. , “Doctors and Drug Companies,” New England Journal of Medicine 351, no. 18 (2004): 1885–1890.

See The PLoS Medicine Editors, supra note 14, at 1299.

See IOM Conflict of Interest Report, supra note 3, at 47.

See id., at 52–56.

See Sage, supra note 12, at 1427.

See IOM Conflict of Interest Report, supra note 3, at 5.

Gray S. , “Attitudes Toward Research Participation and Investigator Conflicts of Interest Among Advanced Cancer Patients Participating in Early Phase Clinical Trials,” Journal of Clinical Oncology 25, no. 23 (2007): 3488–3494.

See id.

See Hampson L. , “Patients' Views on Financial Conflicts of Interest in Cancer Research Trials,” New England Journal of Medicine 355, no. 22 (2006): 2330–2337.

Grady C. , “The Limits of Disclosure: What Research Subjects Want to Know About Investigator Financial Interests,” Journal Law, Medicine & Ethics 34, no. 23 (2006): 592–599.

Weinfurt K. , “Effects of Disclosing Financial Interests on Attitudes toward Clinical Research,” Journal of General Internal Medicine 23, no. 6 (2008): 860–866.

See Gray, supra note 94.

See Grady, supra note 97, at 594.

See Hampson, supra note 96, at 2334.

See supra note 64 and accompanying text.

See, e.g., Stossel, supra note 46.

Williams-Jones B. , “Beyond a Pejorative Understanding of Conflict of Interest,” American Journal of Bioethics 11, no. 1 (2011): 1–2.

See IOM Conflict of Interest Report, supra note 3.

Id., at 52–56.

See supra notes 67 to 70 and accompanying text.

See Guzzo R. A. Katzell R. A. , “Effects of Economic Incentives on Productivity,” in Incentives, Cooperation, and Risk Sharing (Totowa, New Jersey: Rowman and Littlefield: 1987): 107–119, at 109.

See IOM Conflict of Interest Report, supra note 3, at 223–226.

See, e.g., National Bioethics Advisory Commission, Ethical and Policy Issues In Research Involving Human Participants, Bethesda, MD, 2001, at 64.

see IOM, Responsible Research, supra note 18, at 96.

See Saver R. S. , “Medical Research Oversight from the Corporate Governance Perspective: Comparing Institutional Review Boards and Corporate Boards,” William and Mary Law Review 46, no. 2 (2004): 619–730, at 699–705.

See id., at 699–705, 713–719.

See Levinsky , supra note 13, at 760.

See id.;

Jackson C. I. , “Honor in Science,” American Scientist 71, no. 5 (1983): 462–464. Along these lines, recent changes to the standard NIH grant application, made as part of the agency's enhancing peer review process, limit the applicant to listing 15 previously published studies, in an effort to reward for quality over quantity.

See generally National Institutes of Health, Details of Application Changes for Research Grants and Cooperative Agreements available at <http://enhancing-peer-review.nih.gov/docs/application_changes.pdf>(last visited July 24, 2012).

See supra note 24 and accompanying text.

See Cope, supra note 16, at 1616.

See Shepherd , supra note 8;

Kesselheim A. S. , “Managing Financial and Nonfinancial Conflicts of Interest in Healthcare Delivery,” American Journal of Therapeutics 17, no. 4 (2010): 440–443.

Ulrich C. M. , “Respondent Burden in Clinical Research: When Are We Asking Too Much of Subjects?” IRB: Ethics and Human Research 27, no. 4 (2005): 17–20, at 19.

See IOM, Responsible Research, supra note 18, at 104–105.

See Sollitto , supra note 10, at 87.

See Kesselheim , supra note 116, at 442.

see The Center for Health and Pharmaceutical Law and Policy, supra note 63.

See International Committee of Medical Journal Editors, Form For Disclosure Of Potential Conflicts of Interest, Part 4, available at <http://www.icmje.org/coi_disclosure.pdf>(last visited July 24, 2012).

See IOM Conflict of Interest Report, supra note 3, at xii.

See, e.g., Sunstein C. , “On the Expressive Function of Law,” University of Pennsylvania Law Review 144 (1996): 2021–2053.

Hall M. , “Law, Medicine, and Trust,” Stanford Law Review 55, no. 2 (2002): 463–526.