Hostname: page-component-848d4c4894-wg55d Total loading time: 0 Render date: 2024-06-11T03:59:50.603Z Has data issue: false hasContentIssue false

Institutional Conflicts of Interest: Protecting Human Subjects, Scientific Integrity, and Institutional Accountability

Published online by Cambridge University Press:  01 January 2021

Extract

If clinical trials become a commercial venture in which self-interest overrules public interest and desire overrules science, then the social contract which allows research on human subjects in return for medical advances is broken.

Background

In the past two decades, the involvement of non-academic sponsors of biomedical research, particularly clinical trial research, has increased exponentially. The value of such sponsored research is difficult to ascertain. However, it is estimated that, between 1980 and 2003, overall research and development expenditures by US pharmaceutical companies increased from $2 billion to $33 billion and that, in 2001, clinical trial research expenditures in Canada totaled $800 million to $1 billion.

The source of funding for biomedical research has shifted significantly from predominantly government and private foundations to industry. By 2002,70% of funding for clinical trials came from industry. These factors have affected the conduct of research, particularly clinical trial research, in a variety of ways.

Type
Symposium
Copyright
Copyright © American Society of Law, Medicine and Ethics 2004

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Quick, J., “Maintaining the Integrity of the Clinical Evidence Base,” Bull World Health Organization 79, no.12 (2001): at 1093.Google Scholar
PhRMA, 2004 Pharmaceutical Industry Profile, Washington DC: Pharmaceutical Research and Manufacturers of America (2004).Google Scholar
Begin, M., Erola, J., Wells, G., Potworoski, J., Accelerating Access for Patients to Best Medicine: The System and the Challenge (Ottawa: University of Ottawa, 2002).Google Scholar
Bodenheimer, T., “Uneasy Alliance – Clinical Investigators and the Pharmaceutical Industry,” New England Journal of Medicine 342, no. 20 (2000): 15391544.Google Scholar
Blumenthal, D., Campbell, E. G., Anderson, M. S., Causino, N., Louis, K. S., “Withholding Research Results in Academic Life Science: Evidence from a National Survey of Faculty,” Journal of the American Medical Association 277, no.15 (1997): 12241228.CrossRefGoogle Scholar
Bayh-Dole Act, 35 USC 200–212; (1980).Google Scholar
DeAngelis, C. D., “Conflict of Interest and the Public Trust,” Journal of the American Medical Association 284, no. 7 (2000): at 2237–2238; Angell, M., “Is Academic Medicine For Sale?” New England Journal of Medicine 342, no. 20 (2000): 15161518.Google Scholar
Van Der Weyden, M. B., “Confronting Conflict of Interest in Research Organizations: Time for National Action,” Medical Journal of Australia 175, no. 8 (2001): 396397.CrossRefGoogle Scholar
Thompson, D. F., “Understanding Financial Conflicts of Interest,” New England Journal of Medicine 329, no. 8 (1993): 573576.CrossRefGoogle Scholar
See Thompson, , supra note 9.Google Scholar
Martin, J. B., Kasper, D. L., “In Whose Best Interest? Breaching the Academic-Industrial Wall,” New England Journal of Medicine 343, no. 22 (2000): 16461649.CrossRefGoogle Scholar
Levinsky, N. G., “Nonfinancial Conflicts of Interest in Research,” New England Journal of Medicine 347, no. 10 (2002): 759761.CrossRefGoogle Scholar
See Thompson, , supra note 9.Google Scholar
Task Force on Financial Conflicts of Interest in Clinical Research, Protecting Subjects, Preserving Trust, Promoting Progress II: Association of American Medical Colleges, (AAMC: Washington, D.C., 2002).Google Scholar
Task Force on Research and Accountability, Report on Individual and Institutional Financial Conflict of Interest, Washington, DC: Association of American Universities (2001).Google Scholar
Johns, M. M., Barnes, M., Florencio, P. S., “Restoring Balance to Industry-Academia Relationships in an Era of Institutional Financial Conflicts of Interest: Promoting Research While Maintaining Trust,” Journal of the American Medical Association 289, no. 6 (2003): 741746.CrossRefGoogle Scholar
Press, E., Washburn, J., “The Kept University,” Atlantic Monthly 285 (2000): at 39–54.Google Scholar
Lewis, S., Baird, P., Evans, R. G., et al, “Dancing with the Porcupine: Rules for Governing the University-Industry Relationship,” Canadian Medical Association Journal 165, no. 6 (2001): 783785.Google Scholar
Collier, J., Iheanacho, I., “The Pharmaceutical Industry as an Informant,” Lancet 360 no. 9343 (2002): 14051409.CrossRefGoogle Scholar
See Angell, , supra note 7.Google Scholar
OHRP, Financial Relationships in Clinical Research: Issues for Institutions, Clinical Investigators, and IRB’s to Consider when Dealing with Issues of Financial Interests and Human Subject Protection, Washington, D.C.: Office of Human Research Protections (2001).Google Scholar
See Martin, , supra note 11.Google Scholar
See Press, supra note 17.Google Scholar
See Van Der Weyden, , supra note 8.Google Scholar
See Task Force on Financial Conflicts, supra note 14Google Scholar
See Press, Washburn, , supra note 17.Google Scholar
Campbell, E. G., Weissman, J. S., Clarridge, B., Yucel, R., Causino, N., Blumenthal, D., “Characteristics of Medical School Faculty Members Serving on Institutional Review Boards: Results of a National Survey”, Academic Medicine 78, no. 8, (2003): 831836.CrossRefGoogle Scholar
See Johns, , Barnes, , Floencio, , supra note 16.Google Scholar
See OHRP, supra note 21.Google Scholar
Dukes, M. N., “Accountability of the Pharmaceutical Industry,” Lancet 360, no. 9346 (2002): 16821684; Pecoul, B., Chirac, P., Trouiller, P., Pinel, J., Access to Essential Drugs in Poor Countries: A Lost Battle? Journal of the American Medical Association 281, no. 4 (1999): 361–367.CrossRefGoogle Scholar
Angell, M., Relman, A. S., “Prescription for Profit,” Washington Post, June 20, 2001, at A27.Google Scholar
Emanuel, E. J., Teiner, D., “Institutional Conflict of Interest,” New England Journal of Medicine 332, no. 4 (1995): 262267.CrossRefGoogle Scholar
Shalala, D., “Protecting Research Subjects—What Must Be Done,” New England Journal of Medicine 343, no.11 (2000): 808810.CrossRefGoogle Scholar
See Martin, , supra note 11.Google Scholar
Warning Letter from FDA, Center for Biologics Evaluation and Research to Dr. James Wilson, dated March 3, 2000, accessed at http://www.fda.gov/foi/warning_letters/m3435n.pdf on November 5, 2004.Google Scholar
See Shalala, , supra note 33.Google Scholar
See Johns, , Barnes, , Floencio, , supra note 16.Google Scholar
See OHRP, supra note 21.Google Scholar
See Johns, , Barnes, , Floencio, , supra note 16.Google Scholar
Davidoff, F., “Between the Lines: Navigating the Uncharted Territory of Industry- Sponsored Research. A Former Medical Journal Editor Describes How and Why Staff Changed Their Policy on Disclosing Conflicts of Interest,” Health Affairs (Millwood) 21, no. 2 (2002): 235242.CrossRefGoogle Scholar
Davidson, R. A., “Source of Funding and Outcome of Clinical Trials,” Journal of General Internal Medicine 1, no. 3 (1986): 155158: Friedberg, M., Saffran, B., Stinson, T. J., Nelson, W., Bennett, C. L., “Evaluation of Conflict of Interest in Economic Analyses of New Drugs Used in Oncology,” Journal of the American Medical Association 282, no. 15 (1999): 1453–1457; Lexchin, J., Bero, L. A., Djulbegovic, B., Clark, O., “Pharmaceutical Industry Sponsorship and Research Outcome and Quality: Systematic Review,” British Medical Journal 326, no. 7400 (2003): 1167–1170; Cho, M. K., Bero, L. A., “The Quality of Drug Studies Published in Symposium Proceedings,” Annals of Internal Medicine 124, no. 5 (1996): 485–489; Bhandari, M., Busse, J.W., Jackowski, D., et al, “Association between Industry Funding and Statistically Significant Pro-Industry Findings in Medical and Surgical Randomized Trials,” Canadian Medical Association Journal 170, no. 4 (2004): 477–480.CrossRefGoogle Scholar
Bero, L. A., Rennie, D. Influences on the Quality of Published Drug Studies, International Journal of Technology Assessment in Health Care 12, no.2 (1996): 209237.CrossRefGoogle Scholar
See Bero, , supra note 42.Google Scholar
Safer, D. J., “Design and Reporting Modifications in Industry-Sponsored Comparative Psychopharmacology Trials,” Journal of Nervous and Mental Disease 190, no. 9 (2002): 583592.CrossRefGoogle Scholar
Rochon, P. A., Gurwitz, J. H., Simms, R. W., et al, “A Study of Manufacturer-Supported Trials of Nonsteroidal Anti-Inflammatory Drugs in the Treatment of Arthritis,” Archives of Internal Medicine 154, no. 2 (1994): 157163.CrossRefGoogle Scholar
Montaner, J.S., O’Shaughnessy, M. V., Schechter, M. T., “Industry-Sponsored Clinical Research: A Double-Edged Sword,” Lancet 358, no. 9296 (2001): 18931895.CrossRefGoogle Scholar
Ray, W. A., Griffin, M. R., Avorn, J., “Evaluating Drugs after their Approval for Clinical Use,” New England Journal of Medicine 329, no. 27 (1993): 20292032; see Rochon, Gurwitz, , and Simms, , supra note 45CrossRefGoogle Scholar
Marshall, M., Lockwood, A., Bradley, C., Adams, C., Joy, C., Fenton, M., “Unpublished Rating Scales: A Major Source of Bias in Randomized Controlled Trials of Treatments for Schizophrenia,” British Journal of Psychiatry 176 (2000): 249252.CrossRefGoogle Scholar
Carpenter, W., “Industry Phase IV Trials are of Little or No Value: Pro,” Journal of Psychotic Disorders 5, no. 4 (2001): at 3 and 13.Google Scholar
Trivedi, M. H., Rush, A. J., Carmody, T. J., et al, “Do Bupropion SR and Sertraline Differ in their Effects on Anxiety in Depressed Patients?” Journal of Clinical Psychiatry 62, no. 10 (2001): 776781; Carpenter, W. T. Jr., “From clinical trial to prescription,” Archives of General Psychiatry 59, no. 3 (2002): 282–285.CrossRefGoogle Scholar
See Safer, , supra note 44.Google Scholar
Lauritsen, K., Havelund, T., Laursen, L. S., Rask-Madsen, J., “Withholding Unfavorable Results in Drug Company Sponsored Clinical Trials,” Lancet 1, no. 8541(1987): At 1091.Google Scholar
See Ray, , Griffin, , supra note 47; Psaty, B. M., Weiss, N. S., Furberg, C. D., et al, “Surrogate End Points, Health Outcomes, and the Drug-Approval Process for the Treatment of Risk Factors for Cardiovascular Disease,” Journal of the American Medical Association 282, no. 8 (1999): 786790.Google Scholar
Kahn, J. O., Cherng, D. W., Mayer, K., Murray, H., Lagakos, S., “Evaluation of HIV-1 Immunogen, an Immunologic Modifier, Administered to Patients Infected with HIV Having 300 to 549 × 10(6)/4L CD4 Cell Counts: A randomized Controlled Trial,” Journal of the American Medical Association 284, no.17 (2000): 21932202.CrossRefGoogle Scholar
Emanuel, E. J., Wendler, D., Grady, C., “What Makes Clinical Research Ethical?” Journal of the American Medical Association 283, no. 20 (2000): 27012711.CrossRefGoogle Scholar
Editorial, “A Duty to Publish,” Nature Medicine (1998); 4(10): at 1089; Munro, A.J., “Publishing the Findings of Clinical Research,” British Medical Journal 307, no. 6915 (1993): 13401341.Google Scholar
Rosenberg, S. A., “Secrecy in Medical Research,” New England Journal of Medicine 334, no. 6 (1996): 392394; Nadis, S., “US Concern Grows Over Secrecy Clauses,” Nature 398, no.6726 (1999): at 359.CrossRefGoogle Scholar
Chalmers, I., “Underreporting Research is Scientific Misconduct,” Journal of the American Medical Association 263, no. 10 (1990): 14051408.CrossRefGoogle Scholar
See Lexchin, , supra note 41.Google Scholar
Rennie, D., “Thyroid storm,” Journal of the American Medical Association 277, no. 15 (1997): 12381243; See Blumenthal, , Champbell, , Anderson, , Causino, , Louis, , supra note 5.CrossRefGoogle Scholar
See Chalmers, , supra note 58.Google Scholar
Kelch, R. P., “Maintaining the Public Trust in Clinical Research,” New England Journal of Medicine 346, no. 4 (2002): 285287.CrossRefGoogle Scholar
See Bodenheimer, , supra note 4.Google Scholar
See Blumenthal, , Champbell, , Anderson, , Causino, , Louis, , supra note 5.Google Scholar
Simonsen, R. J., “Corporate-Sponsored Research Contracts—an Ethical Minefield,” Quintessence International 27, no. 7 (1996): at 443; See Rennie, , supra note 60.Google Scholar
Phillips, R. A., Hoey, J., “Constraints of Interest: Lessons at the Hospital for Sick Children,” Canadian Medical Association 159, no. 8 (1998): 955957.Google Scholar
Thompson, J., Baird, P., Downie, J., Report of the Committee of Inquiry on the Case Involving Dr. Nancy Olivieri, the Hospital for Sick Children, the University of Toronto, and Apotex Inc. (Toronto: Canadian Association of University Teachers, 2001).Google Scholar
See Angelis, De, supra note 7.Google Scholar
See Task Force on Financial Conflicts, supra note 14.Google Scholar
Finkel, M. J., “Should Informed Consent Include Information on How Research is Funded?” Institutional Review Board 13, no. 5 (1991): 13.Google Scholar
Chaurette, K., Jedrey, C., “Managing Conflicts of Interest in Human Subjects Research,” Medical Research Law & Policy Report 1, no. 14 (2002): 441445.Google Scholar
McCrary, S. V., Anderson, C. B., Jakovljevic, J., et al, “A National Survey of Policies on Disclosure of Conflicts of Interest in Biomedical Research,” New England Journal of Medicine 343, no. 22 (2000): 16211626.CrossRefGoogle Scholar
Lo, B., Wolf, L. E., Berkeley, A., “Conflict-of-interest Policies for Investigators in Clinical Trials,” New England Journal of Medicine 343, no. 22 (2000): 16161620.CrossRefGoogle Scholar
See OHRP, supra note 21.Google Scholar
See Task Force on Financial Conflicts, supra note 14Google Scholar
See OHRP, supra note 21.Google Scholar
See Task Force on Research, supra note 15.Google Scholar
See Task Force on Financial Conflicts, supra note 14.Google Scholar
See Task Force on Financial Conflicts, supra note 14.Google Scholar
See Emanuel, , Steiner, , supra note 32.Google Scholar
See OHRP, supra note 21.Google Scholar
See, Chaurette, Jedrey, , supra note 71.Google Scholar
See Task Force on Financial Conflicts, supra note 14; See Task Force on Research, supra note 15.Google Scholar
van Gijn, J., “The Scribe of Stroke Trials,” European Neurology 49, no. 2 (2003): 125127; Lees, K. R., Orgogozo, J. M., “Acute Stroke: Trial by Jury. The Toothless Tiger (role of the principal investigator)” European Neurology 49, no. 2 (2003): 120–124.CrossRefGoogle Scholar
Morse, M. A., Califf, R. M., Sugarman, J., “Monitoring and Ensuring Safety during Clinical Research,” Journal of the American Medical Association 285, no. 9 (2001): 12011205; Slutsky, A. S., Lavery, J. V., “Data Safety and Monitoring Boards,” New England Journal Medicine 350, no. 11 (2004): 1143–1147CrossRefGoogle Scholar
See Task Force on Financial Conflicts, supra note 14.Google Scholar
See OHRP, supra note 21.Google Scholar
American Association of Medical Colleges, Clinical Trial Contracts: A Discussion of Four Selected Provisions, Washington, DC (2004); DuVal, G., “Institutional Ethics Review of Clinical Study Agreements,” Journal of Medical Ethics 30, no. 1 (2004): 3034.Google Scholar
See OHRP, supra note 21.Google Scholar