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Financial Conflicts of Interest in Human Subjects Research: The Problem of Institutional Conflicts

Published online by Cambridge University Press:  01 January 2021

Mark Barnes  and
Patrik S. Florencio
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Extract

In both academic literature and the media, financial conflicts of interest in human subjects research have come center-stage. The cover of a recent edition of Time magazine features a research subject in a cage with the caption human guinea pigs, signifying perhaps that human research subjects are no more protected from research abuses than are laboratory animals. That magazine issue highlights three well-publicized cases of human subjects research violations that occurred at the University of Oklahoma, the University of Pennsylvania, and Johns Hopkins University.

At St. John Medical Center in Tulsa, Oklahoma, a study that was co-sponsored by the University of Oklahoma Health Sciences Center investigated an experimental vaccine for malignant melanoma. In that case, the chair of the university's institutional review board (IRB) — the committee within each medical institution charged with ethics review of human research projects undertaken at that institution — and the dean of the University's College of Medicine allegedly concealed from both the IRB and the United States Food and Drug Administration (FDA) a report by an outside consulting firm that had found severe deficiencies with the melanoma vaccine study being conducted at the medical center.

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Article
Information
Journal of Law, Medicine & Ethics , Volume 30 , Issue 3 , Fall 2002 , pp. 390 - 402
Copyright
Copyright © American Society of Law, Medicine and Ethics 2002

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References

Lemonick, M.D. Goldstein, A., “At Your Own Risk,” Time, April 14, 2002, at 40-49.Google Scholar
Ironically, in certain respects, animal research is more stringently regulated than is human subjects research. For example, while federal regulations require the Institutional Animal Care and Use Committee (IACUC) — the committee within each medical institution charged with ethics review of animal research projects undertaken at that institution — to review animal research protocols every six months, the continuing review requirement for human research trials may be fulfilled by annual reviews. Moreover, while IACUCs have long been subject to accreditation requirements, attention is only now being directed to accreditation of Institutional Review Boards (IRB).Google Scholar
See Steinbrook, R., “Improving Protection for Research Subjects,” N. Engl. J. Med., 346 (2002): 1425–30;.CrossRefGoogle Scholar
White, E., “House Bill Aims to Protect Human Subjects, Establish Voluntary Accreditation Process,” BNA Medical Research, Law & Policy, 1:5 (2002): 124–25.Google Scholar
In this document, the terms “investigator” and “researcher” are used interchangeably, and include, for all purposes of this article, research staff exercising independent judgment over data gathering, monitoring, analysis, and interpretation, and those involved in the informed consent process with research subjects.Google Scholar
See Office of Human Research Protections, Letters to the University of Oklahoma Health Sciences Center, “Re: Human Research Subject Protections Under Multiple Project Assurance (MPA) M-1448,” dated June 29, 2000, July 7, 2000, July 13, 2000, and October 19, 2000.Google Scholar
Rosenberg, S.A., “Secrecy in Medical Research,” N. Engl. J. Med., 334 (1996): 392–94 See also Cohen, J., “Share and Share Alike is Not Always the Rule in Science,” Science, 268 (1995): 1715–18.Google Scholar
Blumenthal, D. et al. , “University-Industry Research Relationships in Biotechnology: Implications for the University,” Science, 232 (1986): 1361–66; Blumenthal, D. et al. , “Relationships Between Academic Institutions and Industry in the Life Sciences —An Industry Survey,” N. Engl. J. Med., 334 (1996): 368–74.Google Scholar
Thompson, J. Baird, P. Downie, J., Report of the Commission of Inquiry on the Case Involving Dr. Nancy Olivieri, the Hospital for Sick Children, the University of Toronto, and Apotex Inc. (Ottawa: Canadian Association of University Teachers, 2001): at 99.Google Scholar
Hillman, A.I. Pauly, M.V. Kerslein, B., “How do Financial Incentives Affect Physician's Clinical Decisions and the Financial Performance of Health Maintenance Organizations,” N. Engl. J. Med., 321 (1989): 86–92;.Google Scholar
Hillman, B.J. et al. , “Frequency and Costs of Diagnostic Imaging in Office Practice: A Comparison of Self-Referring and Radiologist Referring Physicians,” N. Engl. J. Med., 323 (1990): 1604–08;.CrossRefGoogle Scholar
Swedlow, A. et al. , “Increased Costs and Rates of Use in the California Workers' Compensation System as a Result of Self-Referral by Physicians,” N. Engl. J. Med., 327 (1992): 1502–06;.CrossRefGoogle Scholar
Wilkinson, P., “‘Self Referral’: A Potential Conflict of Interest,” British Medical Journal (1993): 1083–84.Google Scholar
Chren, M.M. Landenfeld, C.S., “Physicians Behavior and their Interactions With Drug Companies: A Controlled Study of Physicians Who Requested Additions to a Hospital Formulary,” JAMA, 271 (1994): 684–89.CrossRefGoogle Scholar
Wazana, A., “Physicians and the Pharmaceutical Industry: Is a Gift Just Ever a Gift?,” JAMA, 283 (2000): 373–80;.CrossRefGoogle Scholar
Kassirer, J.P., “A Piece of My Mind: Financial Indigestion,” JAMA, 284 (2000): 2156–57;.Google Scholar
Rothman, D.J., “Medical Professionalism —Focusing on the Real Issues,” N. Engl. J. Med., 342 (2000): 1284–86;.Google Scholar
Waud, D.R., “Pharmaceutical Promotions — A Free Lunch,” N. Engl. J. Med., 327 (1992): 351–53.Google Scholar
Andaleeb, S.S. Tallman, R.F., “Physician Attitudes Toward Pharmaceutical Sales Representatives,” Health Care Management Review, 20 (1995): 68–76; Thomson, A.N. Craig, B.J. Barham, P.M., “Attitudes of General Practitioners in New Zealand to Pharmaceutical Representatives,” British Journal of General Practice, 44 (1994): 220–23.CrossRefGoogle Scholar
See generally Cho, M.K. Bero, L.A., “The Quality of Drug Studies Published in Symposium Proceedings,” Annals of Internal Medicine, 124 (1996): 485–89; Barnes, D.E. Bero, L.A., “Industry Funded Research and Conflict of Interest: An Analysis of Research Sponsored by the Tobacco Industry Through the Center for Indoor Air Research,” Journal of Health Politics, Policy & Law, 21 (1996): 515–42;.CrossRefGoogle Scholar
Anderson, J.J. Felson, D.T. Meenan, R.F., “Secular Changes in Published Clinical Trials of Second-Line Agents in Rheumatoid Arthritis,” Journal of Arthritis & Rheumatism, 34 (1991): 1304–09.Google Scholar
Stelfox, H.T. et al. , “Conflict of Interest in the Debate Over Calcium-Channel Antagonists,” N. Engl. J. Med., 332 (1998): 101–06.CrossRefGoogle Scholar
Davidson, R.A., “Source of Funding and Outcome of Clinical Trials,” Journal of General Internal Medicine, 1 (1986): 155–58;.CrossRefGoogle Scholar
Rochon, P.A. et al. , “A Study of Manufacturer Supported Trials of Non-Steroidal Anti-Inflammatory Drugs in the Treatment of Arthritis,” Archives of Internal Medicine, 154 (1994): 157–63.Google Scholar
Friedberg, M. et al. , “Evaluation of Conflict of Interest in Economic Analyses of New Drugs Used in Oncology,” JAMA, 282 (1999): 1453–57.CrossRefGoogle Scholar
Barnes, D.E. Bero, L.A., “Why Review Articles on the Health Effects of Passive Smoking Reach Different Conclusions,” JAMA, 279 (1998): 1566–70.Google Scholar
Booth, W., “Conflict of Interest Eyed at Harvard,” Science, 242 (1988): 1497–99.CrossRefGoogle Scholar
Thompson, D.F., “Understanding Financial Conflicts of Interest,” N. Engl. J. Med., 329 (1993): 573–76, at 573.Google Scholar
Rothman, K.J., “The Ethics of Research Sponsorship,” Journal of Clinical Epidemiology, 44, Supplement (1991): 25–28; Rothman, K.J., “Conflicts of Interest: The New McCarthyism in Science,” JAMA, 269 (1993): 2782–84.CrossRefGoogle Scholar
Friedman, P.J., “The Troublesome Semantics of Conflict of Interest,” Ethics Behavior, 2 (1992): 245–51; Cohen, J.J., “Trust Us to Make a Difference: Ensuring Public Confidence in the Integrity of Clinical Research,” Academic Medicine, 76 (2001): 209–14.Google Scholar
See Thompson, , supra note 18, at 574.Google Scholar
See generally 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;.Google Scholar
Barnes, M. Krauss, S., “Conflicts of Interest in Human Research: Risks and Pitfalls of ‘Easy Money’ in Research Funding,” BNA's Health Law Report, 9:35 (2000): 1378–86.Google Scholar
Barnes, M. Florencio, P.S., “Investigator, IRB and Institutional Financial Conflicts of Interest in Human Subjects Research: Past, Present and Future,” Seton Hall Law Review (publication anticipated in 2003).Google Scholar
IRB member conflicts of interest are regulated, theoretically, for all conflict of interest purposes, both financial and nonfinancial. Yet the Public Health Service and the Food and Drug Administration regulations that apply this “zero-tolerance” policy to IRB member conflict of interests are written generally, without exact definitions of what constitutes either a financial or nonfinancial conflict of interest for these purposes.Google Scholar
Association of American Universities, Task Force Report on Individual and Institutional Conflicts of Interest (Washington, D.C.: Association of American Universities, October, 2001): 1–22, at 10, available at <http://www.aau.edu/research/COI.01.pdf>..>Google Scholar
Korn, D., “Conflicts of Interest in Biomedical Research,” JAMA, 284 (2000): 2234–37.Google Scholar
National Human Research Protections Advisory Committee, Letter to the Honorable Tommy, G. Thompson, Secretary of the U.S. Department of Health and Human Services, “Re: HHS' Draft Interim Guidance: Financial Relationships in Clinical Research: Issues for Institutions, Clinical Investigators and IRBs to Consider When Dealing With Issues of Financial Interests and Human Subject Protection,” dated August 8, 2001, at 9 (on file with author).Google Scholar
Stolberg, S.G., “The Biotech Death of Jesse Gelsinger,” New York Times Magazine, Nov. 28, 1999, available at <http://nytimes.com/library/magazine/home/19991128mag*stolberg.html>..>Google Scholar
Beardsley, T., “Gene Therapy Setback: A Tragic Death Clouds the Future of an Innovative Treatment Method,” Scientific American, 282 (2000): 36–37.CrossRefGoogle Scholar
See Lemonick, , supra note 1.Google Scholar
American Society of Gene Therapy, Policy of the American Society on Gene Therapy on Financial Conflict of Interest in Clinical Research (Adopted April 5, 2000), available at <http://www.asgt.org/policy/index.html>..>Google Scholar
45 C.F.R. §; 46.107(e) (2002);Google Scholar
21 C.F.R. §; 56.107(e) (2002).Google Scholar
Wilson, D. Heath, D., “The Blood-Cancer Experiment: Patients Never Knew the Full Danger of Trials They Staked Their Lives On,” Seattle Times, March 11, 2001, at A1;. Wilson, D. Heath, D., “With a Year or Two to Live, Woman Joined Test in Which She Was Misled — and Died,” Seattle Times, March 13, 2001, at A1;.Google Scholar
Wilson, D. Heath, D., “The Hutch Zealously Guards its Secrets,” Seattle Times, March 15, 2001,): at A1.Google Scholar
Angell, M., “Is Academic Medicine For Sale?,” N. Engl. J. Med., 342 (2000): 1516–18, at 1517 (“[h]ow can [academic medical institutions] justify rigorous conflict of interest policies for individual researchers when their own ties are so extensive? Some academic institutions have entered into partnerships with drug companies to set up research centers and teaching programs in which students and faculty members essentially carry out industry research”).CrossRefGoogle Scholar
Relman, A.S., “Economic Incentives in Clinical Investigation,” N. Engl. J. Med., 320 (1989): 933–34 Kassirer, J.P., “Medicine at Center Stage,” N. Engl. J. Med., 328 (1993): 1268–69;.Google Scholar
Shalala, D., “Protecting Research Subjects — What Must be Done,” N. Engl. J. Med., 343 (2000): 808–10.Google Scholar
Kassirer, J.P. Angell, M., “Financial Conflicts of Interest in Biomedical Research,” N. Engl. J. Med., 329 (1993): 570–71, at 571 (“when researchers [and research institutions] choose to invest in health-related companies rather than in other types of business, it raises the question of whether they are attempting to profit from the specialized knowledge they gain in the course of performing research”).CrossRefGoogle Scholar
Kassirer, J.P., “Pseudoaccountability,” Annals of Internal Medicine, 134 (2001): 587–90.CrossRefGoogle Scholar
In fact, some calls for federal oversight have already been made. The U.S. National Bioethics Advisory Commission, for example, has called for federal legislation to create a National Office for Human Research Oversight to oversee all research involving human subjects, including disclosure and management of conflicts of interest. See National Bioethics Advisory Commission, Ethical and Policy Issues in Research Involving Human Participants (Rockville, Maryland: The Commission, 2001), available at <http://www.georgetown.edu/research/nrcbl/human/overvoll.html>..>Google Scholar
See also Wood, A.J.J. Stein, C.M. Woosley, R., “Making Medicines Safer — The Need for an Independent Drug Safety Board,” N. Engl. J. Med., 339 (1998): 1851–54.Google Scholar
Association of American Universities, supra note 25, at 12.Google Scholar
During the editorial process, the Association of American Medical Colleges released a report on institutional financial interests in human subjects research.Google Scholar
See Association of American Medical Colleges (October 2002): 1–14, available at <http://www.aamc.org/members/coitf/2002coireport.pdf>..>Google Scholar
National Association of Securities Dealers, NASD Rule 2711, Research Analysts and Research Reports, available at <http://www.nasdr.com/pdf-text/rf02_21_final.pdf>; Securities and Exchange Commission, Amendments to NYSE Rules 472 and 351, available at <http://www.nyse.com/regulation/regulation.html>.;+Securities+and+Exchange+Commission,+Amendments+to+NYSE+Rules+472+and+351,+available+at+.>Google Scholar
Association of American Universities, supra note 25, at 13.Google Scholar
Id.Google Scholar
Internal Revenue Service, Excise Taxes on Excess Benefit Transactions, 65 Federal Register at 3076 et seq. (January 23, 2002). 44. The intermediate sanctions rules provide that when a disqualified person benefits from an excess benefit transaction, that disqualified person will be liable for an excise tax equal to 25 percent of the excess benefit. If the excess benefit is not corrected (i.e., returned to the institution), the disqualified person can be liable for an additional excise tax of 200 percent of the excess benefit.Google Scholar
See Id.Google Scholar
Korn, , supra note 26.Google Scholar
Moore v. Regents of the University of California, 793 P.2d 479 (Cal. 1990).Google Scholar
DAB v. Brown, 570 N.W2d 168 (Minn. Ct. App. 1997).CrossRefGoogle Scholar
Rodwin, M.A., “Physicians' Conflicts of Interest: The Limitations of Disclosure,” N. Engl. J. Med., 321 (1989): 1405–08;.CrossRefGoogle Scholar
Miller, T.E. Sage, WM., “Disclosing Physician Financial Incentives,” JAMA, 281 (1999): 1424–30.CrossRefGoogle Scholar
Miller, T.E. Horowitz, C.R., “Disclosing Doctors' Incentives: Will Consumers Understand and Value the Information?,” Health Affairs, 19 (2000): 149–55.Google Scholar
Kassirer, J.P., “Financial Conflict of Interest: An Unresolved Ethical Frontier,” American Journal of Law & Medicine, 27, nos. 2&3 (2001): 149–62, at 151.Google Scholar
Moses, H. Martin, J.B., “Academic Relationships With Industry: A New Model for Biomedical Research,” JAMA, 285 (2001): 933–35.Google Scholar
Bodenheimer, T., “Uneasy Alliance: Clinical Investigators and the Pharmaceutical Industry,” N. Engl. J. Med., 342 (2000): 1539–44.Google Scholar
Wolfe, S.M., “Why do American Drug Companies Spend More Than $12 Billion a Year Pushing Drugs?” Journal of General Internal Medicine, 11 (1996): 637–39.CrossRefGoogle Scholar
Randall, T., “Kennedy Hearings Say No More Free Lunch — or Much Else — From Drug Firms,” JAMA, 265 (1991): 440.CrossRefGoogle Scholar
See Bodenheimer, , supra note 52.Google Scholar
See Id.Google Scholar
Blumenthal, D. et al. , “Withholding Research Results in Academic Life Sciences: Evidence From a National Survey of Faculty,” JAMA, 277 (1997): 1224–28 Chalmers, I., “Underreporting Research is Scientific Misconduct,” JAMA, 263 (1990): 1405–08.CrossRefGoogle Scholar
Gibson, E. Baylis, F. Lewi, S., “Dances With the Pharmaceutical Industry,” Canadian Medical Association Journal, 166 (2002): 448–50; Skolnick, A.A., “Drug Firm Suit Fails to Halt Publication of Canadian Health Technology Report,” JAMA, 280 (1998): 683–84.Google Scholar
Slater, E.E., “IRB Reform,” N. Engl. J. Med., 346 (2002): 1402–04 at 1403 (noting that “… the increasing number and complexity of protocols are taxing the capability of local IRBs.”).CrossRefGoogle Scholar
Emanuel, E.J. Steiner, D., “Institutional Conflict of Interest,” N. Engl. J. Med., 332 (1995): 262–67 at 265 (“… some members of the [IRB] might work for the department that stood to benefit financially from the clinical research, and others might benefit indirectly from the institution's royalties. Finally, the public perceives these boards as internal rather than external bodies. Just as citizens may be suspicious of the thoroughness of a government agency's review of its own behavior, there may be little confidence in an [IRB's] judgment when the institution has a financial interest in the research”).Google Scholar
See National Human Research Protections Advisory Committee, supra note 27, at 6 (“[c]onflict of interest analysis should take account of, and contain ‘compelling and necessary’ exceptions for, situations in which physicians who treat unusual conditions invent new devices or develop other interventions, and yet have significant financial interests in those techniques, interventions, or devices. In these cases, guidance should not discourage these physicians from inventing new devices and developing new interventions and therapies, and should not prohibit these physicians from acting as clinical investigators, particularly in the initial stages of investigation, since they may be in the best position to undertake critical research with a high assurance of safety for research subjects”).Google Scholar
See Association of American Medical Colleges, Protecting Subjects, Preserving Trust, Promoting Progress —- Policy and Guidelines for the Oversight of Individual Financial Interests in Human Subjects Research (December 2001): 1–25, at 7, available at <http://www.aamc.org/members/coitf/firstreport.pdf>,(“[i]n the event of compelling circumstances, an individual holding significant financial interests in human subjects research may be permitted to conduct the research. Whether the circumstances are deemed compelling will depend in each case upon the nature of the science, the nature of the interest, how closely the interest is related to the research, and the degree to which the interest may be affected by the research”).,(“[i]n+the+event+of+compelling+circumstances,+an+individual+holding+significant+financial+interests+in+human+subjects+research+may+be+permitted+to+conduct+the+research.+Whether+the+circumstances+are+deemed+compelling+will+depend+in+each+case+upon+the+nature+of+the+science,+the+nature+of+the+interest,+how+closely+the+interest+is+related+to+the+research,+and+the+degree+to+which+the+interest+may+be+affected+by+the+research”).>Google Scholar
It has been recommended that pharmaceutical companies, device manufacturers, biotechnology companies, and other research sponsors maintain a “searchable web-based registry of researchers and practicing physicians with whom they have an established financial relationship.” See Kassirer, , supra note 50, at 151. This searchable registry could be extended to also list corporate and personal institutional financial conflicts of interest when disclosure to the sponsor is recommended by the IRP.Google Scholar
As we noted above, the editors of many leading biomedical journals have adopted the position that they must reveal to readers the financial incentives underlying the articles they publish so that readers can interpret the findings presented in the articles in light of the financial incentives. When recommended by the independent review panel, significant institutional financial incentives might also be disclosed to journal editors who could then publish this information alongside the article.Google Scholar
Miller, F.G. Rosenstein, D.L. DeRenzo, E.G., “Professional Integrity in Clinical Research,” JAMA, 280 (1998): 1449–54;.Google Scholar
Yarborough, M. Sharp, R.R., “Restoring and Preserving Trust in Biomedical Research,” Academic Medicine, 77 (2002): 8–14.CrossRefGoogle Scholar
Palmisano, P. Edelstein, J., “Teaching Drug Promotion Abuses to Health Care Profession Students,” Journal of Medical Education, 55 (1980): 453–55.Google Scholar
See Blumenthal, et al. , supra note 6.Google Scholar