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Avoiding Exploitation in Phase I Clinical Trials: More than (Un)Just Compensation

Published online by Cambridge University Press:  01 January 2021

Matt Lamkin  and
Carl Elliott
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Abstract

Lowering compensation to research subjects to protect them from “undue inducement” is a misguided attempt to shoehorn a concern about exploitation into the framework of autonomy. We suggest that oversight bodies should be less concerned about undue influence than about exploitation of subjects. Avoiding exploitation in human subjects research requires not only increasing compensation, but enhancing the dignity of research participation.

Type
Symposium Articles
Information
Journal of Law, Medicine & Ethics , Volume 46 , Issue 1: The Future of Informed Consent in Research & Translational Medicine: A Century of Law, Ethics & Innovation , Spring 2018 , pp. 52 - 63
Copyright
Copyright © American Society of Law, Medicine and Ethics 2018

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References

Coyle and Sharpe, “Maniacs in a Living Hell,” The Insane (But Hilarious) Minds of Coyle & Sharpe, available at <https://www.youtube.com/watch?v=_GG9zSr9CkY> (last visited August 29, 2017).+(last+visited+August+29,+2017).>Google Scholar
See, e.g., Office for Human Research Protections, Protecting Human Research Subjects: Institutional Review Board Guidebook (Washington D.C.: U.S. Government Printing Office, 1993): at Chapter 3, Section B, 33.Google Scholar
St. Clair, E. W., “The Calm After the Cytokine Storm: Lessons From the TGN1412 Trial,” Journal of Clinical Investigation 118, no. 4 (2008): 1344–1347.CrossRefGoogle Scholar
Almeida, L., Azevedo, B., Nunes, T., Vaz-da-Silva, M., and Soares-da-Silva, P., “Why Healthy Subjects Volunteer for Phase I Studies and How They Perceive Their Participation,” European Journal of Clinical Pharmacology 63, 11 (2007):1085–1094; T. Monahan and J. Fisher, “I'm Still a Hustler’: Entrepreneurial Responses to Precarity by Participants in Phase I Clinical Trials,” Economy and Society 44, no. 4 (2015): 545-566.Google Scholar
Abadie, R., The Professional Guinea Pig (Durham, N.C.: Duke University Press, 2010): at 54–57; C. Elliott, “Guinea-Pigging,” The New Yorker, January 7, 2008, 36-41; M. Cottingham and J. Fisher, “Risk and Emotion Among Healthy Volunteers in Clinical Trials,” Social Psychology Quarterly 79, no. 3 (2016): 222-242.Google Scholar
See, e.g., Nelson, R., Beauchamp, T., Miller, V., Reynolds, W., Ittenbach, R., and Luce, M., “The Concept of Voluntary Consent,” American Journal of Bioethics 11, no. 8 (2011): 6–16, at 9 (“The federal regulations governing research in the United States require investigators to ‘minimize the possibility of’ undue inducement, but they do not define, analyze, or explain this notion…”).Google Scholar
Lynch, H., “Protecting Human Research Subjects as Human Research Workers,” in Cohen, I. Glenn and Lynch, Holly Fernandez, eds., Human Subjects Research Regulation: Perspectives on the Future (Cambridge: MIT Press, 2014): Chapter 21, at 332 (“The bigger problem for research subjects is that the regulatory system in some ways encourages their exploitation by effectively precluding high payments.”).Google Scholar
See, e.g., Resnik, D. B., “Research Participation and Financial Inducements,” American Journal of Bioethics 11, no. 2 (2001): 54–56, at 55.CrossRefGoogle Scholar
National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, The Belmont Report (Washington, D.C.: Government Printing Office, 1979): at 8.Google Scholar
Id.Google Scholar
Faden, R. and Beauchamp, T., “Coercion, Manipulation, and Persuasion,” in A History and Theory of Informed Consent (New York: Oxford University Press, 1986): Chapter 10, at 337–381.Google Scholar
Id. at 358-360.Google Scholar
Id. at 358.Google Scholar
See, e.g., Council of International Organizations of Medical Sciences (CIOMS) and the World Health Organization (WHO), International Ethical Guidelines for Biomedical Research involving Human Subjects, Geneva, 2002: 46; Department of Health and Human Services (DHHS), “Protection of Human Subjects of Research (‘The Common Rule’)” 45 C.F.R. § 46.116; Food and Drug Administration, Department of Health and Human Services (DHHS), “Payment to Research Subjects – Information Sheet,” available at <http://www.fda.gov/RegulatoryInformation/Guidances/ucm126429.htm> (last visited May 2, 2017).+(last+visited+May+2,+2017).>Google Scholar
Faden and Beauchamp, supra note 11, at 360.Google Scholar
Largent, E., Grady, C., Miller, F. and Wertheimer, A., “Misconceptions About Coercion and Undue Influence,” Bioethics 27, no. 9 (2013): 500–507.CrossRefGoogle Scholar
For example, see Appelbaum, P., Lidz, C., and Klitzman, R., “Voluntariness of Consent to Research: A Conceptual Model,” Hastings Center Report 39, no. 1 (2009): 30–39; R. Nelson and J. Merz, “Voluntariness of Consent for Research: An Empirical and Conceptual Review,” Medical Care 40, no. 9 Supplement (2002): V-69-V-80; Nelson et al., supra note 6.CrossRefGoogle Scholar
M. Cottingham and J. Fisher, supra note 6.Google Scholar
World Medical Association, Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects, 2000, Article 17 (“[m]edical research involving a disadvantaged or vulnerable population or community is only justified if…there is a reasonable likelihood that this population or community stands to benefit from the results of the research.”). See also Belmont Report, supra note 9, at 6; 45 C.F.R. § 46.111(3); E. Emanuel, D. Wendler, and C. Grady, “What Makes Clinical Research Ethical?,” JAMA 283, no. 20 (2000): 2701-2711, at 2704-2705.Google Scholar
See, e.g., Lemmens, T. and Elliott, C., “Guinea Pigs on the Payroll: The Ethics of Paying Research Subjects,” Accountability in Research: Policies and Quality Assurance 7, no. 1 (1999): 3–20, at 13; J. Fisher, Medical Research for Hire: The Political Economy of Pharmaceutical Clinical Trials (New Brunswick, N.J.: Rutgers University Press, 2009) at 151-152; A. Iltis, “Payments to Normal Healthy Volunteers in Phase 1 Trials: Avoiding Undue Influence While Distributing Fairly the Burdens of Research Participation,” Journal of Medicine and Philosophy 34, no. 1 (2009): 68-90, at 72.Google Scholar
Fisher, supra note 20, at 130. See also Stunkel, L., Benson, M., McLellan, L., Sinaii, N., Bedarida, G., Emanuel, E., and Grady, C., “Comprehension and Informed Consent: Assessing the Effect of a Short Consent Form,” IRB: Ethics & Human Research 32, no. 4 (2010): 1–9, at 6; Iltis, supra note 20, at 72; M. Cottingham and J. Fisher, supra note 6; J. Fisher and C. Kalbaugh, “Challenging Assumptions About Minority Participation in U.S. Clinical Research,” American Journal of Public Health 101, no. 12 (2011): 2217-2222.Google Scholar
For example, see Elliott, C., The Best-Selling, Billion-Dollar Pills Tested on Homeless People, Medium (2014), available at <https://medium.com/matter/did-big-pharma-test-your-meds-on-homeless-people-a6d8d3fc7dfe> (last visited May 2, 2017); D. Evans, M. Smith, and L. Willen, “Big Pharma's Shameful Secret,” Bloomberg Markets, December 2005, at 36-62; L. Cohen, “Lilly's ‘Quick Cash’ to Habitués of Shelters Vanishes Quickly,” Wall Street Journal, November 14, 1996, at A1.+(last+visited+May+2,+2017);+D.+Evans,+M.+Smith,+and+L.+Willen,+“Big+Pharma's+Shameful+Secret,”+Bloomberg+Markets,+December+2005,+at+36-62;+L.+Cohen,+“Lilly's+‘Quick+Cash’+to+Habitués+of+Shelters+Vanishes+Quickly,”+Wall+Street+Journal,+November+14,+1996,+at+A1.>Google Scholar
Elliott, C. and Abadie, R., “Exploiting a Research Underclass in Phase 1 Clinical Trials,” New England Journal of Medicine 358, no. 22 (2008): 2316–2317.Google Scholar
Nelson et al., supra note 6, at 9.Google Scholar
Institutional Review Board Guidebook, supra note 2, at 33.Google Scholar
Id. at 34.Google Scholar
Largent et al., supra note 16, at 500.Google Scholar
Dickert, N., Emanuel, E., and Grady, C., “Paying Research Subjects: An Analysis of Current Policies,” Annals of Internal Medicine 136, no. 5 (2002): 368–373, 372.CrossRefGoogle Scholar
Largent, E., Grady, C., Miller, F., and Wertheimer, A., “Money, Coercion, and Undue Inducement: A Survey of Attitudes About Payments to Research Subjects,” IRB 34, no. 1 (2012): 1–8.Google Scholar
Id.Google Scholar
See Lynch, supra note 7; Lemmens and Elliott, supra note 20, at 13-14.Google Scholar
Lynch, H., “Human Research Subjects as Human Research Workers,” Yale Journal of Health Policy, Law & Ethics 14 (2014): 123–193, 157 (“[F]ear of undue inducement plays no role whatsoever in the legal regulation of wages paid to workers. In fact, worklaw imposes no ceiling – explicit or implicit – on how much workers may be paid…”).Google Scholar
Johnson v. International Business Machines Corp., 891 F. Supp. 522, 531 (N.D. Cal. 1995).Google Scholar
“The fairness of the resulting exchange is often a critical factor in cases involving threats.” American Law Institute, Restatement (Second) of Contracts (1979), at § 176, comment a. Courts are also more likely to invalidate a contract because of a party's incapacity when the terms of the agreement appear unfair to the impaired party. Id. at § 15(2).Google Scholar
Id. at § 208 and § 208 comment c. Although inadequate consideration is not sufficient on its own to invalidate a contract, “gross disparity in the values exchanged may be an important factor in a determination that a contract is unconscionable.” Id. at § 208 comment c. See also Eric A. Posner, “Contract Law in the Welfare State: A Defense of the Unconscionability Doctrine, Usury Laws, and Related Limitations on the Freedom to Contract,” Journal of Legal Studies 24, no. 2 (1995): 283-319, at 304 (noting that the doctrine of substantive unconscionability “condemns contracts involving substantial disparities between the contract price and the market price” and that the doctrine “dovetail[s] with the conventional view that courts should strike down involuntary contracts (as… price disparity is strong evidence of bargaining abuse)”).Google Scholar
Lynch notes some interesting historical examples of laws that have limited wages — including, for example, some “passed by some state legislatures in the South after emancipation for reasons that were decidedly anti-worker.” As Lynch notes, “[i] n none of these examples, however, is payment limited out of fear that workers will suffer from undue inducement.” Lynch, supra note 32, at 160.Google Scholar
Faden and Beauchamp, supra note 11, at 360.Google Scholar
Steinman v. Malamed, 185 Cal.App.4th 1550, 1559 (2010). Wertheimer, A., Coercion (Princeton, N.J.: Princeton University Press, 1990): at 41 (noting that in contract law “there is generally no duress if A's proposal is not wrongful – even if it serves to create B's dilemma.”).Google Scholar
Johnson, supra note 33, at 529.Google Scholar
Restatement (Second) of Contracts, supra note 34, at § 176 comment a (in considering whether a contract should be invalidated on the basis of duress or undue influence, “the fairness of the resulting exchange is often a critical factor.”).Google Scholar
Resnik, supra note 8, at 55.Google Scholar
198 U.S. 45 (1905).Google Scholar
Adkins v. Children's Hospital, 261 U.S. 525 (1923); Hammer v. Dagenhart, 247 U.S. 251 (1918); Adair v. United States, 208 U.S. 161 (1908).Google Scholar
Wertheimer, A., “Exploitation in Clinical Research,” in Emanuel, E., Grady, C., Crouch, R., Lie, R., Miller, F., and Wendler, D., eds., The Oxford Textbook of Clinical Research Ethics (New York: Oxford University Press, 2008): at 202.Google Scholar
Jones, J. H., “The Tuskegee Syphilis Experiment,” in The Oxford Textbook of Clinical Research Ethics, supra note 44, at 90.Google Scholar
Wertheimer, supra note 44, at 203.Google Scholar
Cottingham and Fisher, supra note 6.Google Scholar
Werthheimer, A., Rethinking the Ethics of Clinical Research (New York: Oxford University Press, 2011), at 201.Google Scholar
Office of the Legislative Auditor, State of Minnesota, A Clinical Drug Study at the University of Minnesota Department of Psychiatry: The Dan Markingson Case (2015) [hereinafter Legislative Auditor Report], available at <www.auditor.leg.state.mn.us/sreview/Markingson.pdf> (last visited August 29, 2017).+(last+visited+August+29,+2017).>Google Scholar
Wertheimer, supra note 44, at 205.Google Scholar
Emanuel, E., “Undue Inducement: Nonsense on Stilts?,” American Journal of Bioethics 5, no. 5 (2005): 9–13.CrossRefGoogle Scholar
President's Commission for the Study of Bioethical Issues, Moral Science: Protecting Participants in Human Subjects Research, June 2012, at 8, 15, available at <https://bioethicsarchive.georgetown.edu/pcsbi/sites/default/files/Moral%20Science%20June%202012.pdf> (last visited August 29, 2017). (last visited August 29, 2017).' href=https://scholar.google.com/scholar?q=President's+Commission+for+the+Study+of+Bioethical+Issues,+Moral+Science:+Protecting+Participants+in+Human+Subjects+Research,+June+2012,+at+8,+15,+available+at++(last+visited+August+29,+2017).>Google Scholar
Id.Google Scholar
The Lewin Group, Task Order Proposal No. 2, “Care/Compensation for Injuries in Clinical Research,” Draft of the final report prepared for the Department of Health and Human Services Office of the Assistant Secretary for Planning and Evaluation, Falls Church, VA: The Lewin Group, May 18, 2005. (Contract no. HHS 100-03-0005). See also C. Elliott, “Justice for Injured Research Subjects,” New England Journal of Medicine 367, no. 1 (2012): 6-8.Google Scholar
Resnik, D. B., Parasidis, E., Carroll, K., Evans, J.M., Pike, E. R., and Kissling, G. E., “Research-Related Injury Compensation Policies of U.S. Research Institutions,” IRB 36, no. 1 (2014): 12–19.Google Scholar
Id.Google Scholar
Tamariz, L., Palacio, A., Robert, M., and Marcus, E. N., “Improving the Informed Consent Process for Research Subjects with Low Literacy: A Systematic Review,” Journal of General Internal Medicine 28, no. 1 (2006): 121–126.Google Scholar
Fisher, J., “Feeding and Bleeding: The Institutional Banalization of Risk to Healthy Volunteers in Phase I Pharmaceutical Clinical Trials,” Science, Technology, & Human Values 40, no. 2 (2015): 199–226.Google Scholar
van den Bogert, C. A., Souverein, P. C., Brekelmans, C. T. M., Janssen, S. W. J., Koëter, G. H., Leufkens, H. G. M., and Bouter, L. M., “Non-Publication Is Common Among Phase 1, Single-Center, Not Prospectively Registered, or Early Terminated Clinical Drug Trials,” PLOS One 11, no. 1 (2006); Public Health Service Act, 42 U.S.C. § 282 (j) (2007).Google Scholar
Declaration of Helsinki, supra note 19, at 35.Google Scholar
Office of Inspector General, Department of Health and Human Services, The Food and Drug Administration's Oversight of Clinical Trials, September 2007, available at <https://oig.hhs.gov/oei/reports/oei-01-06-00160.pdf> (last visited August 29, 2017). (last visited August 29, 2017).' href=https://scholar.google.com/scholar?q=Office+of+Inspector+General,+Department+of+Health+and+Human+Services,+The+Food+and+Drug+Administration's+Oversight+of+Clinical+Trials,+September+2007,+available+at++(last+visited+August+29,+2017).>Google Scholar
Emanuel, E. J., Bedarida, G., Macci, K., Gabler, N. B., Rid, A., Wendler, D., “Quantifying the Risks of Non-Oncology Phase I Research in Healthy Volunteers: Meta-Analysis of Phase I Studies,” BMJ 350 (2015): 1–9.CrossRefGoogle Scholar
Emanuel, E., “Ending Concerns about Undue Inducement,” Journal of Law, Medicine, & Ethics 32, no. 1 (2004): 100–105, at 104.CrossRefGoogle Scholar
Wilson, R. F., “The Death of Jesse Gelsinger: New Evidence of the Influence of Money and Prestige in Human Research,” American Journal of Law & Medicine 36, 2-3 (2010): 295–325; H. Edgar and D. J. Rothman, “The Institutional Review Board and Beyond: Future Challenges to the Ethics of Human Experimentation,” Milbank Quarterly 73, no. 4 (1995): 489-506, at 493; D. Wilson and D. Heath, “Patients Never Knew the Full Danger of Trials They Staked Their Lives On,” Seattle Times, March 11, 2001, at A1; A. Michaud, “UC Drops Controversial Psychoses Tests: Critics Contend Studies Unethical,” Cincinnati Enquirer, May 6, 1999, at 1; A. Malhotra, D. A. Pinals, C. M. Adler, I. Elman, A. Clifton, D. Pickar, and A. Breier, “Ketamine-Induced Exacerbation of Psychotic Symptoms and Cognitive Impairment in Neuroleptic-Free Schizophrenics,” Neuropsychopharmacology 17, no. 3 (1997): 141-150; S. M. Southwick, J. H. Krystal, J. D. Bremner, C.A. Morgan, A.L. Nicolaou, L.M. Nagy, D.R. Johnson, G.R. Heninger, D.S. Charney, “Noradrenergic and Serotonergic Function in Post Traumatic Stress Disorder,” Archives of General Psychiatry 54, no. 8 (1997): 749-758; Legislative Auditor Report, supra note 49, at 14; J. Baillon, “U of M Drug Study Criticism Grows,” KMSP TV, May 19, 2014, available at <www.fox9.com/health/1647039-story> (last visited August 29, 2017); C. Elliott, “U Owes Mistreated Psychiatric Subjects an Apology,” Minneapolis Star Tribune, October 7, 2015, available at <http://www.startribune.com/u-owes-mis-treated-psychiatric-subjects-an-apology/331165371/> (last visited August 29, 2017); C. Elliott, “Why Research Oversight Bodies Should Interview Research Subjects,” IRB: Ethics and Human Research 39, no. 2 (2017), 8-13.Google Scholar
Legislative Auditor Report, supra note 49, at 20; Lamkin, M. and Elliott, C., “Involuntarily Committed Patients as Prisoners,” Richmond Law Review 51, no. 101 (2017): 114–115.Google Scholar
Rosenthal, E., “New York Seeks to Tighten Rules on Medical Research,” New York Times, September 27, 1996, at B4; E. Rosenthal, “British Rethinking Rules After Ill-Fated Drug Trial,” New York Times, April 8, 2006, at A1; G. Kolata, “Johns Hopkins Admits Fault in Fatal Experiment,” New York Times, July 17, 2001, at A16; J. K. Wall and J. Tuohy, “Suicide Brings Changes to Lilly Drug Trials,” Indianapolis Star, February 11, 2004, at A1; C. Elliott, supra note 22; K. Messmer and J. Blasingim, “An Analysis of Specific Phase I Safety Issues,” Regulatory Rapporteur 14, no. 2 (2017): 23-27.Google Scholar
See Obasogie, O. K., “Prisoners as Human Subjects: A Closer Look at the Institute of Medicine's Recommendations to Loosen Current Restrictions on Using Prisoners in Scientific Research,” Stanford Journal of Civil Rights and Civil Liberties 6, no. 41 (2010): 75–77; Evans et al., supra note 22, at 39; T. Lemmens and P. Miller, “The Human Subjects Trade: Ethical and Legal Issues Surrounding Recruitment Incentives,” Journal of Law, Medicine & Ethics 31, no. 3 (2003): 398-419.Google Scholar
Sample, R. J., Exploitation: What It Is and Why It's Wrong (Oxford: Rowman & Littlefield Publishers, 2003): at 57.Google Scholar
Wortham, J., “Use of Homeless as Internet Hot Spots Back-fires on Marketer,” New York Times, March 12, 2012, at B1.Google Scholar
Overall, C., “What's Wrong With Prostitution? Evaluating Sex Work,” Signs: Journal of Women in Culture and Society 17, no. 4 (1992): 705–724.CrossRefGoogle Scholar
Wolfe, T., The Right Stuff (New York: Farrar, Straus and Giroux, 1979): at 100, 148.Google Scholar
Abadie, R., The Professional Guinea Pig: Big Pharma and the Risky World of Human Research Subjects (Durham, N.C.: Duke University Press, 2005): at 7–8, 48, 162; M. Murrmann, “I Was a Teenage Guinea Pig!” Washington City Paper, November 22, 1996, available at <http://www.washingtoncitypaper.com/news/article/13011942/i-was-a-teenage-guinea-pig> (last visited August 29, 2017).+(last+visited+August+29,+2017).>Google Scholar
Helms, R., ed. Guinea Pig Zero: An Anthology for the Journal of Human Research Subjects (New Orleans, LA: Garrett County Press, 2005): at 207, 200.Google Scholar
Id.Google Scholar
Evans et al., supra note 22.Google Scholar
Evans, D. and Smith, M., “Three Drug Testers Claim SFBC Threatened Them,” Seattle Times, November 20, 2005, available at <http://www.seattletimes.com/business/three-drug-testers-claim-sfbc-threatened-them/> (last visited August 29, 2017).+(last+visited+August+29,+2017).>Google Scholar
Pike, E., “Recovering From Research: A No-Fault Proposal to Compensate Injured Research Participants,” American Journal of Law, Medicine & Ethics 38, no. 1 (2012): 7–62.CrossRefGoogle Scholar