The Human Subjects Trade: Ethical and Legal Issues Surrounding Recruitment Incentives

Whitaker R. , “Lure of Riches Fuels Testing,” The Boston Globe, November 17, 1998, at A-1; Eichenwald K. Kolata G. , “Drug Trials Hide Conflicts for Doctors,” The New York Times, May 16, 1999, at 1.1. See also Andrews L.B. , “Money is Putting People at Risk in Biomedical Research,” Chronicle of Higher Education, 46, no. 27 (2000): B-4.

Eichenwald Kolata , supra note 1.

Dembner A. , “Who's Protecting the Children? Drug Research Raises Concerns About Policy and Penalties,” The Boston Globe, March 25, 2001, at A-1.

Department of Health and Human Services, Office of Inspector General, Recruiting Human Subjects: Pressures in Industry-sponsored Research (2000): At 8, 25.

Few articles focus exclusively on recruitment incentives. See Lind S. , “Finder's Fees for Research Subjects,” N. Engl. J. Med., 303 (1990): 192–95; “Is the Practice of Offering Finder's Fees for Subject Recruitment Appropriate? Is the Practice Widespread or Unique to My Institution? What is the Proper Role of the IRB? What is the Role of the Institution?,” IRB: A Review of Human Subjects Research, 12, no. 4 (1990): 6; DeRenzo E.G. , “Coercion in the Recruitment and Retention of Human Research Subjects, Pharmaceutical Industry Payments to Physician-Investigators, and the Moral Courage of the IRB,” IRB: A Review of Human Subjects Research, 22, no. 2 (2000): 1–5; Miller P.B. Lemmens T. , “Finder's Fees and Therapeutic Obligations,” Geriatrics and Aging, 5, no. 1 (2002): 66–69; Caulfield T. Griener G. , “Conflicts of Interest in Clinical Research: Addressing the Issue of Physician Remuneration,” Journal of Law, Medicine & Ethics, 30, no. 2 (2002): 305–08. Other articles do refer to some of the issues in varying degrees of detail. See, e.g., Dresser R. , “Payment to Research Participants: The Importance of Context,” American Journal of Bioethics, 1, no. 2 (2001): 47; Rothstein M.A. , “Currents in Contemporary Ethics: The Role of IRBs in Research Involving Commercial Biobanks,” Journal of Law, Medicine & Ethics, 30, no. 1 (2002): 105–08, at 106, and other articles on conflict of interest cited herein.

Goldner J.A. , “Dealing with Conflicts of Interest in Biomedical Research: IRB Oversight as the Next Best Solution to the Abolition Approach,” Journal of Law, Medicine & Ethics, 28, no. 4 (2000): 379–404, at 382.

See Department of Health and Human Services, supra note 5, at 16; Department of Health and Human Services, Office of Inspector General, Recruiting Human Subjects: Sample Guidelines for Practice (2000): 1–23, at 8. See also Torrey E.F. , “The Going Rate on Shrinks: Big Pharma and the Buying of Psychiatry,” The American Prospect, 13, no. 13 (2002). A study by Boyd Elizabeth A. Bero Lisa A. , in which they analyzed disclosures of financial ties with industry by researchers at the University of California, revealed that 34 percent of disclosed relationships involved paid speaking engagements, providing speakers with annual revenues ranging between $200 and $20,000. See Boyd E.A. Bero L.A. , “Assessing Faculty Relationships with Industry: A Case Study,” JAMA, 184, no. 17 (2000): 2209–14, at 2211.

See Boyd Bero , supra note 8, at 2211–12 for a case analysis of such relationships. Boyd and Bero report that 33 percent of disclosed relationships involved paid consulting, for which annual revenues ranged between $1,000 and $120,000.

Department of Health and Human Services, supra note 5, at 1, 15.

Kelch R.P. , “Maintaining the Public Trust in Clinical Research,” N. Engl. J. Med., 346, no. 4 (2002): 285–87; Martin J.B. Kasper D.L. , “In Whose Best Interest? Breaching the Academic-Industrial Wall,” N. Engl. J. Med., 343, no. 22 (2000): 1646–49; Angell M. , “Is Academic Medicine for Sale?,” N. Engl. J. Med., 342, no. 20 (2000): 1516–18; Lewis S. , “Dancing with the Porcupine: Rules for Governing the University-Industry Relationship,” Canadian Medical Association Journal, 165, no. 6 (2001): 783–85; Rettig R.A. , “The Industrialization of Clinical Research,” Health Affairs, 19, no. 2 (2000): 129–45; Morin K. , “Managing Conflicts of Interest in the Conduct of Clinical Trials,” JAMA, 287 (2002): 78–84, at 78.

Morin , supra note 11, at 78.

Larkin M. , “Clinical Trials: What Price Progress?,” The Lancet, 354 (1999): 1534.

Morin , supra note 11, at 78.

Id., Rettig , supra note 11.

Larkin , supra note 13, at 1534.

Morin , supra note 11, at 78; see also Bodenheimer T. , “Uneasy Alliance — Clinician Investigators and the Pharmaceutical Industry,” N. Engl. J. Med., 342, no. 20 (2000): 1539–44, at 1539.

Shamoo A.E. , “Adverse Events Reporting — The Tip of an Iceberg,” Accountability in Research, 8 (2001): 197–218.

It is hard to say how realistic this number is. Clearly, the United States leads Canada in research funding by a considerable margin. Furthermore, in the United States many may participate in research to obtain access to treatment.

Regulations Amending the Food and Drug Regulations (1024 - Clinical Trials), P.C. 2001–1042, Canada Gazette, 2001 Part II Page 1116, at 1139.

Lewis , supra note 11, at 783.

Shamoo , supra note 18, at 197.

Goldner , supra note 7, at 382.

Bodenheimer , supra note 17, at 1539.

The issue of payment of subjects is clearly related to that of payment of finder's fees. Finder's fees are intended to attract researchers to recruitment activity; payments to subjects are intended to convince subjects to participate. We focus in this article on the pressure exercised on researchers and on how this affects their legal and ethical duties. For a discussion of payment of subjects, see Grady C. , “Money for Research Participation: Does it Jeopardize Informed Consent?” American Journal of Bioethics, 1, no. 2 (2001): 40–44 and commentaries; Lemmens T. Elliott C. , “Guinea Pigs on the Payroll: The Ethics of Paying Research Subjects,” Accountability in Research, 7 (1999): 3–20.

Quoted in Dembner , supra note 4.

Whitaker , supra note 1.

Department of Health and Human Services, supra note 5, at 13.

Bodenheimer , supra note 17, at 1539.

Department of Health and Human Services, supra note 5, at 18.

Goldner , supra note 7, at 382. See also Bodenheimer , supra note 17, at 1541.

National Institutes for Health, Conference on Human Subject Protection and Financial Conflicts of Interest (2000) (conference transcript): At 45.

Bodenheimer , supra note 17, at 1540.

Rettig , supra note 11, at 138.

Id., at 139; Department of Health and Human Services, supra note 5, at 11.

Whitaker , supra, note 1.

Macklin R. , quoted in Larkin , supra note 13.

See generally Department of Health and Human Services, supra note 5, at 20–26; see also Shalala D. , “Protecting Research Subjects — What Must be Done,” N. Engl. J. Med., 343, no. 11 (2000): 808–10, at 808. See also Morin , supra note 11, at 80.

See sources cited at note 1, supra.

National Institutes of Health, supra note 35, at 14; see also Goldner , supra note 7, at 381.

Department of Health and Human Services, supra note 5, at 25.

Personal communication from Dr. Barry Goldlist to the author (TL), December 10, 2001.

Larkin , supra note 13, at 1534; see also Miller F.G. Shorr A.F. , “Ethical Assessment of Industry-Sponsored Clinical Trials: A Case Analysis,” Chest, 121, no. 4 (2002): 1337–42, at 1337.

See Montaner J.S.G. O'Shaughnessy M.V. Schechter M.T. , “Industry-Sponsored Clinical Research: A Double-Edged Sword,” The Lancet, 358 (2001): 1893–95; Naylor C.D. , “Early Toronto Experience with New Standards for Industry-Sponsored Clinical Research: A Progress Report,” Canadian Medical Association Journal, 166, no. 4 (2002): 453–56.

Bodenheimer , supra note 17, at 1541–42. See also Davidoff F. , “Between the Lines: Navigating the Uncharted Territory of Industry-Sponsored Research,” Health Affairs 21, no. 2 (2002): 235–42; “Look, No Strings: Publishing Industry-Funded Research,” Canadian Medical Association Journal, 165, no. 6 (2001): 733 (editorial).

Bodenheimer , supra note 17, at 1541–42.

Department of Health and Human Services, supra note 5, at 17.

See, for example, reports on the Nancy Olivieri affair: Report to the Board of Trustees of the Hospital for Sick Children, “Clinical Trials of L1 (Deferiprone) at the Hospital for Sick Children: A Review of Facts and Circumstances,” (December 8, 1998), available at <http://www.sickkids.on.ca/L1trials/revcontents.asp>, Thompson J. Baird P. Downie J. , The Olivieri Report: The Complete Text of the Report of the Independent Inquiry Commissioned by the Canadian Association of University Teachers (Toronto: James Lorimer, 2001); Naimark A. Knoppers B.M. Lowy F.H. , “Commentary on Selected Aspects of the Report of the Committee of Inquiry on the Case of Dr. Olivieri, the Hospital for Sick Children, the University of Toronto, and Apotex Inc.” (December 2001), formerly available at <http://www.sickkids.on.ca/MediaRoom/CAUTfinal2ed.pdf> (last visited January 22, 2002); Thompson J. Baird P. Downie J. , “Supplement to the 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.,” (January, 30 2002), available at <http://www.dal.ca/∼jgdownie/coi/SupplementtoInqReport.pdf>.

Goldner , supra note 7, at 385.

For an interesting argument on how payment of subjects affects the moral status and social conception of research participation, see Chambers T. , “Participation as Commodity, Participation as Gift,” American Journal of Bioethics, 1, no. 2 (2001): 48.

Orlowski R. Wateska L. , “The Effects of Pharmaceutical Firm Enticements on Physician Prescribing Patterns,” Chest, 102 (1992): 270–73.

See generally Goldner , supra note 7, at 390; and Glass K.C. Lemmens T. , “Conflict of Interest and Commercialization of Biomedical Research: What is the Role of Research Ethics Review?” in Caulfield T. Williams-Jones B. , eds., The Commercialization of Genetic Research: Ethical, Legal and Policy Issues (New York, NY: Kluwer, 1999): At 79.

Goldner , supra note 7, at 390; Fleetwood J. , “Conflicts of Interest in Clinical Research: Advocating for Patient-Subjects,” Widener Law Symposium Journal, 8 (2001): 105–14, at 112.

Food and Drug Administration, Information Sheets: Guidance for Institutional Review Boards and Clinical Investigators (1998).

Department of Health and Human Services, supra note 5, at 26.

The DHHS regulations are at 42 C.F.R. Subpart F; the FDA regulations at 21 C.F.R. Parts 54, 312, 314, 320, 330, 601, 807, 812, 814, and 860

See Association of American Medical Colleges, Task Force on Financial Conflicts of Interest in Clinical Research, Protecting Subjects, Preserving Trust, Promoting Progress: Policy and Guidelines for the Oversight of Individual Financial Conflict of Interest in Human Subjects Research (2001), available at <http://www.aamc.org/members/coitf/start.htm> at 5–6. The shortcomings of the regulations are also recognized in DHHS Draft Interim Guidance, available at <http://ohrp.osophs.dhhs.gov/nhrpac/mtg12–00/finguid.htm>.

For details, see Shalala , supra note 41, at 810.

DHHS Draft Interim Guidance, supra note 61; and Department of Health and Human Services, Draft “Financial Relationships and Interests in Research Involving Human Subjects: Guidance for Human Subject Protection,” Federal Register, 68, no. 61 (March 31, 2003), at 15456–60.

See Weiss R. , “New HHS Panel Makeup Draws Ire of Patient Advocates,” The Washington Post, January 5, 2003, at A-09.

Task Force on Financial Conflicts of Interest in Clinical Research, supra note 61; and Association of American Medical Colleges, Task Force on Financial Conflict of Interest in Clinical Research, Institutional Conflict of Interest, Protecting Subjects, Preserving Trust, Promoting Progress II: Principles and Recommendations for Oversight of an Institution's Financial Interests in Human Subjects Research (Association of American Medical Colleges, 2001).

Regulations Amending the Food and Drug Regulations, supra note 20, at 1131.

Dickens B.M. , “Conflict of Interest in Canadian Health Care Law,” American Journal of Law & Medicine, 21, nos. 2&3 (1995): 259–80, at 274.

Medical Research Council of Canada (MRC), Natural Sciences and Engineering Research Council of Canada (NSERC), and Social Sciences and Humanities Research Council of Canada (SSHRC), Tri-Council Policy Statement (Ottawa: Minister of Supply and Services, 1998): Art. 4.1. In the section dealing with clinical trials, the Policy Statement also explicitly requires REBs to examine the budgets of clinical trials (see art. 7.3).

Id. at art. 7.3.

Id. at art. 2.6 (e).

For more on the limits on the responsibility of REBs, see Keiger D. De Pasquale S. , “Trials & Tribulation,” Johns Hopkins Magazine, available at <http://www.jhu.edu/∼jhumag/0202web/trials.html>.

For similar arguments in consideration of the U.S. system, see Fleetwood , supra note 56.

See generally Department of Health and Human Services, Office of Inspector General, Institutional Review Boards: A Time for Reform (1998); Koski G. , “Risks, Benefits, and Conflicts of Interest in Human Research: Ethical Evolution in the Changing World of Science,” Journal of Law, Medicine & Ethics, 28, no. 4 (2000): 330–31; Shalala , supra note 41, at 809.

Lemmens T. Freedman B. , “Ethics Review for Sale? Conflict of Interest and Commercial Research Review Boards,” Milbank Quarterly, 78 (2000): 547–84.

Regulations Amending the Food and Drug Regulations, supra note 20 at 1143, 1132.

See Ferris L.E. , “Industry-Sponsored Pharmaceutical Trials and Research Ethics Boards: Are They Cloaked in Too Much Secrecy?” Canadian Medical Association Journal, 166, no. 10 (2002): 1279–80, at 1279.

Weijer C. , “Placebo Trials and Tribulations,” Canadian Medical Association Journal, 166, no. 5 (2002): 603–04.

MRC, NSERC, SSHRC, supra note 68, at art.7.4 (discussing placebo controls).

Department of Health and Human Services, supra note 73: Department of Health and Human Services, Office of Inspector General, Institutional Review Boards: The Emergence of Independent Boards (1998); Department of Health and Human Services, Office of Inspector General, Institutional Review Boards: Their Role in Reviewing Approved Research (1998); Department of Health and Human Services, Office of Inspector General, Institutional Review Boards: Promising Approaches (1998); U.S. National Bioethics Advisory Commission, Ethical and Policy Issues in Research Involving Human Participants (2001); Cho M.K. Billings P. , “Conflict of Interest and Institutional Review Boards,” Journal of Investigative Medicine, 45, no. 4 (1997): 154–59.

Lemmens T. Thompson A. , “Non-Institutional Research Review Boards in North America: A Critical Appraisal and Comparison with IRBs,” IRB: A Review of Human Subjects Research, 23, no. 2 (2001): 1–12.

Lemmens Freedman , supra note 74; Cho Billings , supra note 79; Francis L. , “IRBs and Conflicts of Interest,” in Spece R.S. Shimm D.S. Buchanan A.E. , eds., Conflicts of Interest in Clinical Practice and Research (New York, NY: Oxford University Press, 1996): 418.

Ferris , supra note 76, at 1279.

Hirtle M. Lemmens T. Sprumont D. , “A Comparative Analysis of Research Ethics Review Mechanisms and the ICH Good Clinical Practice Guideline,” European Journal of Health Law, 7 (2000): 265–92.

See Cho Billings , supra note 79, at 155; Glass Lemmens , supra note 55.

Lemmens Freedman , supra note 74.

See Cho Billings , supra note 79, at 156; see also Fleetwood , supra note 56, at 111.

See generally Hirtle Lemmens Sprumont , supra, note 83.

Translation by author (TL), Swiss Bundesgerichts, Second Public Law Division, July 4, 2003, Freiburger Ethik-Kommission International v. Regierungsrat des Kantons Basel-Landscbaft (2A.450/2002) available at <http://wwwsrv.bger.ch/cgi-bin/AZA/MapProcessorCGI_AZA?mapfile=pull/ConvertDocFrameCGI.map&ri=fr&lang=fr&ds=AZA_pull&d=04.07.2003_2A.450%2f2002&pa=1%7e2a%2b450%2b2002%4073%7e&>. A commentary on this case can be found in A. Jost, Arrêt du 4 juillet de la Hème cour de droit public du Tribunal fédéral, Freiburger Ethik-Kommission International c. Bâle-Campagne (2A.450/2002)” Revue suisse de droit de la santé, 1 (2003) (forthcoming).

Grimes v. Kennedy Krieger Institute, 782 A.2d 807 (Md. 2001), reconsideration denied (2001).

Dickens , supra note 67, at 274

MRC, NSERC, SSHRC, supra note 68, at art. 4.1.

Canadian Medical Association, Physicians and the Pharmaceutical Industry (Ottawa: Canadian Medical Association, 2001).

Id. at paragraph 3.

Id. at paragraph 11.

American Medical Association, Council on Ethical and Judicial Affairs, “Conflicts of Interest: Biomedical Research [opinion E-8.031],” in American Medical Association, Council on Ethical and Judicial Affairs, Code of Medical Ethics: Current Opinions (Chicago, IL: American Medical Association, 2000).

American Medical Association, Council on Ethical and Judicial Affairs, “Fee Splitting: Referrals to Health Care Facilities,” (opinion E-6.03) in American Medical Association, Council on Ethical and Judicial Affairs, Code of Medical Ethics: Current Opinions (Chicago, IL: American Medical Association, 2000).

American Medical Association, Council on Ethical and Judicial Affairs, Finder's Fees: Payment for the Referral of Patients to Clinical Research Studies (report #65) (Chicago: American Medical Association, 1994).

False Claims Act, 31 U.S.C.§ 3729(a) (2001).

Anti-Kickback Statute, 42 U.S.C.§ 1320a-1327b (2001).

Kalb P.E. Koehler K.G. , “Legal Issues in Scientific Research,” JAMA, 287, no. 1 (2002): 85–91.

Id. at 86.

Id. at 87–89.

45 C.F.R.§ 46.

21 C.F.R.§ 50.

42 C.F.R.§ 50.604.

Kalb Koehler , supra note 103, at 89.

Id. at 86 and 89.

Id. at 89.

Choudhry S. Brown A.D. Choudhry N.K. , “Kickbacks to Physicians and Physician Self-Referral in Canada: Unregulated Private Markets?” (manuscript in preparation).

Medicine Act, 1991 R.R.O. 856/93, amended to R.R.O. 53/95. We are indebted to Sujit Choudhry for bringing these provisions to our attention.

Health Professions Procedural Code, being Schedule II to the Regulated Health Professions Act, 1991, R.S.O. 1991, c.18.

R.R.O. 241/94, amending 114/94.

For a short overview of the law on this issue, see Picard E.I. Robertson G.B. , Legal Liability of Doctors and Hospitals in Canada , (3d ed.) (Toronto: Carswell, 1996): At 149–52; and Glass K.C. Lemmens T. , “Research Involving Humans,” in Downie J. Caulfield T. Flood C. , Canadian Health Law and Policy, (2d ed.) (Toronto: Butterworths, 2002): 459–500, at 493–97.

Reibl v. Hughes, [1980] 114 D.L.R. (3d) 1 (Can.).

Hopp v. Lepp [1980] 2 S.C.R. 192 (Can.).

Picard Robertson , supra note 116, at 484.

See Dickens , supra note 67.

Halushka v. University of Saskatchewan , [1965] 52 W.W.R. 608, at 616.

Id. at 617.

[1989] R.J.Q. 731.

Moore v. Regents of the University of California , 793 P.2d 479 (Cal. 1990).

Id. at 483.

See Dickens , supra note 67, at 273.

Rodwin M.A. , “Strains in the Fiduciary Metaphor: Divided Physician Loyalties and Obligations in a Changing Health Care System,” American Journal of Law & Medicine, 21, nos. 2&3 (1995): 241–57, at 243–44.

Norberg v. Wynrib[1992] 92 D.L.R. (4th) 449 (Can.); see also Dickens , supra note 67, at 261–62.

Norberg , supra note 131, at 486.

Id. at 487.

Id. at 486.

Id. at 489.

Weinrib E.J. , “Restitutionary Damages as Corrective Justice,” Theoretical Inquiries in Law, 1, no. 1 (2000): 1–37, at 33.

Whiten v. Pilot Insurance Co. [2002] 209 D.L.R. (4th) 257 (Can.), at 274.

Dickens , supra note 67, at 264.

Rodwin , supra note 130, at 246.

Fleetwood , supra note 56, at 109

Picard Robertson , supra, note 116, at 484.

Kalb Koehler , supra note 103.

Id. at 88.

See Davis K. Roy J. , “Fraud in the Canadian Courts: An Unwarranted Expansion of the Scope of the Criminal Sanction,” Canadian Business Law Journal, 30 (1998): 210–38.

R. v. Gaetz [1993] 84 C.C.C. (3d) 351 (Can.).

R. v. Zlatic [1993] 19 C.R. (4th) 230 (Can.); see also R. v. Lajoie [1999] 136 C.C.C. (3d) 84 (Que. C.A.).

R. v. Emond [1997] 117 C.C.C. (3d) 276 (Que. C.A.).

R. v. Campbell [1986], 29 C.C.C. (3d) 7 (Can.).

R. v. Knowtes [1979] 51 C.C.C. (2d) 237 (Ont. C.A.), at 241.

R. v. Roy [1994], 70 O.A.C. 127; for an interesting discussion of the ramifications of this case, see Davis Roy , supra note 146, at 219–22.

Korn D. , “Conflicts of Interest in Biomedical Research,” JAMA, 284, no. 17 (2000): 2234–37; Morin , supra note 11, at 81–83; Rettig , supra note 11, at 140–43; Lewis , supra note 11.

Naylor , supra note 47; Lewis , supra note 11; Cho M.K. , “Policies on Faculty Conflicts of Interest at US Universities,” JAMA, 284 (2000): 2237–38.

See, e.g., University of Toronto Faculty of Medicine, Offer and Acceptance of Finder's Fees for the Recruitment of Research Subjects, available at <http://eir.library.utoronto.ca/medicine/calendar/reg_offer.cfm>; University of Washington, Policy Prohibiting the Use of Enrollment Incentives in Human Subjects Research, available at <http://www.washington.edu/research/gcs/enrollment.html/>; University of Rochester Office of Research and Project Administration, University of Rochester Policy on Enrollment Incentive Payments by or to University Clinical Trial Researchers, available at <http://www.Rochester.edu/ORPA/policies/incenpay.pdf>; see also Van McCrary S. , “A National Survey of Policies on Disclosure of Conflicts of Interest in Biomedical Research,” N. Engl. J. Med., 343 (2000): 1621, at 1623.

Van McCrary , supra note 155.

Id. at 1623.

Id.; Lo B. Wolf L.E. Berkeley A. , “Conflict-of-interest Policies for Investigators in Clinical Trials,” N. Engl. J. Med., 343 (2000): 1616; Cho M.K. , supra note 154; Boyd Bero , supra note 8.

See Hirtle Lemmens Sprumont , supra note 83.

Schomisch J.W. , “Senate Panel Told Federal Agency Needed for Human Protection in Clinical Trials,” RAPS News, April 24, 2002, available at <http://www.raps.org/news/senate04232002.cfm>; see also Shalala , supra note 41, at 809.

Research Revitalization Act of 2002, 107th Congress (2002) (Discussion Draft), at§ 2(a)(14).

Id. at § 2(b)(1–3).

Id. at Title II,§ 201(e)(2)(C) and (f)(2).

Id. at Title III,§ 301 (a) (1–2).

Id. at Title IV.§ 401 (a) (1–3).

Id. at Title IV,§ 401 (b) (1) and (c).

Id. at Title IV,§ 401 (d).

Id., Title V,§ 501 (a) and (e).

H.D. 917, 143 Sess. (Md. 2002).