Exploitation in payments to research subjects

Bioethics

Volumn 25, Issue 4, 2011, Pages 209-219

  Phillips, Trisha ^a  

^a MISSISSIPPI STATE UNIVERSITY   (United States)

Author keywords

Clinical trials; Exploitation; Inducements; Justice; Payments; Research ethics; Undue inducements

Indexed keywords

ARTICLE; ECONOMICS; ETHICS; HUMAN; HUMAN EXPERIMENT; HUMAN RIGHTS; PATIENT SELECTION; PERSUASIVE COMMUNICATION; RESEARCH SUBJECT; SALARY AND FRINGE BENEFIT;

COERCION; HUMAN EXPERIMENTATION; HUMAN RIGHTS; HUMANS; PATIENT SELECTION; RESEARCH SUBJECTS; SALARIES AND FRINGE BENEFITS;

EID: 79955037686     PISSN: 02699702     EISSN: 14678519     Source Type: Journal    
DOI: 10.1111/j.1467-8519.2009.01717.x     Document Type: Article

References (49)

1. Carl Elliot discusses the near perfect storm these forces create in Guinea-Pigging. SeeC. Elliot200836 41
2. C. WeijerLetter to the Editor.N Engl J Med1999341201550 1551
3. This paper discusses the issue as it pertains to adult subjects participating in: (1) domestic trials, or (2) international trials conducted among countries with relatively equal social and economic demographics. Payments to children or their guardians, and payments between researchers in developed countries and subjects in undeveloped countries are separate issues and will not be addressed in this paper
4. R. AshcroftMoney, Consent, and Exploitation in Research. AJOB20011262 63
5. Guinea Pig Zero available at:[Accessed 18 June 2008]; Elliot, op. cit. note 1; N. Kass, E. Fuchs, L. Martinez et al. Autonomy, Justice, and Phase 1 Research: A Pilot Study of the Motivations and Experiences of healthy Volunteers Enrolled in Phase 1 Drug Development Studies. Presented at the Annual Meeting for the Association for Bioethics and Humanities, October2003
6. C. GradyAndersen & Weijer, op. cit. note 4; N. Dickert & What's the Price of a Research Subject? Approaches to Payment for Research ParticipationN Engl J Med1999341198 203
7. R. Levine1986Ethics and Regulation of Clinical Research, 2nd edn. New Haven, Conn: Yale University Press
8. R. MacklinDue and Undue inducementsOn Paying Money to Research SubjectsIRB 1981311 6
9. R. Faden & T. Beauchamp1986A History and Theory of Informed ConsentNew York: Oxford University Press
10. The American Heritage College Dictionary. 3rd edn. Boston: Houghton Mifflin Company1997
11. A. Wertheimer1996Exploitation. Princeton: Princeton University Press
12. For the purpose of simplifying this discussion, the subject will be on one side of the research transaction, and the term researcher will refer to all parties on the other side. This could include coordinators, investigators, other clinical research staff, for profit and not-for-profit sponsoring institutions at local, regional, national, and international levels
13. M. WalzerFor a more thorough defense of this position, see: T. Phillips. 2006. Diagnosing Exploitation: Justice and Human Subjects Research. (unpublished manuscript); See also: Spheres of Justice: A Defense of Pluralism and Equality. Basic Books1983
14. Kass et al.,Recruitment of Research Subjects.SoCRA Source200127
15. For a more thorough defence of this micro-level criterion of fairness, see Phillips, op. cit. note11
16. Guinea Pig Zen, op. cit. note 5
17. Personal communication with a researcher who prefers to remain anonymous.
18. Andersen & Weijer, op. cit. note 4; Dickert & Grady, op. cit. note 6; Grady, op. cit. note 6: Dickert et al., op. cit. note 6; Dunn & Gordon, op. cit. note 6; Saunders & Sugar, op. cit. note 6; and Thompson, op. cit. note 6
19. In the interest of sparing the reader too many acronyms, I-R-B will refer to both Institutional Review Boards (IRBs) and Research Ethics Boards (REBs)
20. This list does not include reimbursement for actual expenses because this is not payment for participation
21. For more on fairness in transactions of this type, see Phillips, op. cit. note 11
22. Levine, op. cit. note 7; Macklin, op. cit. note 7; McNeil. op. cit. note 7; Faden & Beauchamp, op. cit. note 7; this position has also been challenged by Martin Wilkinson, Andrew Moore, Ezekiel Emanuel, and Franklin Miller. See: M. Wilkinson & A. Moore. Inducement in Research. Bioethics199711374 389
23. C. GradyMoney for Research ParticipationDoes it Jeopardize Informed Consent? AJOB20011240 44
24. Dickert and Grady reported that the average was $10/hour in 1999; according to the United States Department Of Labor the average was $17/hour in See Dickert & Grady, op. cit. note 62007
25. Resnik argues that the sick subject's ability to make informed choices about participation in research may already be compromised by the therapeutic misconception, and this pre-existing vulnerability may amplify the unduly inducing effect of money. Therefore, healthy subjects should be paid a fair wage but sick subjects should be paid less, or in some cases, nothing at all. See Resnik, op. cit. note 4
26. J. MenikoffJust CompensationPaying Research Subjects Relative to the Risks They Bear.AJOB200156 58
27. Andersen & Weijer, op. cit. note
28. Calculating overtime pay at time and a half for all hours worked over 40 in a single week, as suggested by the United States Department of Labor. See: Employment Standards Administration of the United States Department Of Labor. Fact Sheet 23: Overtime Pay Requirements of the FLSA. Available at2008
29. Testwiththebest.com is a recruiting website for Covance, a clinical research organization. Advertisement referenced is Protocol 7978-100 Group B2. Available at[Accessed 15 Mar2008
30. Calculated at $17/hour for the first 40 hours of a week and $25.5/hour for all remaining hours. Carl Elliot also notes that payments as high as $7,500 are not unusual. See Elliot, op. cit. note 1.
31. S. Halpern, J.H.T. Karlawish, D. Casarett et al.The threshold beyond which a payment becomes unduly inducive has not been empirically identified. In fact, studies published by Halpern and colleagues and Bentley and Thacker suggest that the threshold is very high, if it even exits at all. See: Empirical Assessment of Whether Moderate Payments Are Undue Inducements for Participation in Clinical Trials. Arch Intern Med2004164801 802
32. Levine, op. cit. note 7; Macklin, op. cit. note 7; McNeil, op. cit. note 7; Faden & Beauchamp, op. cit. note 7
33. A. BallantyneBenefits to Research Subjects in International Trials: Do They Reduce Exploitation or Increase Undue Inducement? Dev World Bioeth20061 14
34. Here I assume that international and domestic regulations and guidelines are evidence of established orthodoxy
35. The Australian regulations state: The consent of a person to participate in research must not be subject to any coercion, or to any inducement or influence which could impair its voluntary character. See: National Health and Medical Research Council of Australia. National Statement on Ethical Conduct in Research Involving Humans19992009
36. Council of Europe states: The ethics committee must be satisfied that no undue influence, including that of a financial nature, will be exerted on persons to participate in research. See: Council of Europe. 2005. Additional Protocol to the Convention on Human Rights and Biomedicine Concerning Biomedical Research. Strasbourg. Article 12. Available at: Accessed 10 Feb 2009].Canada's Tri-Council Policy states: Payment structures for research participation that might place undue pressure on research subjects either to join or remain within a research project should be prevented. See: Medical Research Council of Canada, Natural Sciences and Engineering Research Council of Canada and Social Sciences and Humanities Research Council of Canada. Tri-council Policy Statement. Section D. Available at: Accessed 20 June2008
37. The Office for Human Research Protections (OHRP). IRB Guidebook. ch. 4, section I
38. CIOMS, op. cit. note 39, G7
39. OHRP, op. cit. note 40, chapter 3, sections F and G; CIOMS, op. cit. note 39, section G7
40. G. Annas & M. Grodin. For example, the Nazi experiments on concentration camp inmates and the Tuskegee syphilis study. See: 1992. The Nazi Doctors and the Nuremberg Code. New York: Oxford University Press; and J. Jones.Bad Blood: the Tuskegee Syphilis Experiment. New York: The Free Press1981
41. Transactions can still be exploitative even when the exploitee benefits. Wertheimer uses the term mutually beneficial to refer to this type of exploitation. See: Wertheimer, op. cit. note 10
42. As defined in 45CFR46.102(i), Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. Hereafter trials that present minimal risk or less than minimal risk will be referred to as low risk trials. See: Department of Health and Human Services. Code of Federal Regulations Title 45 Part 46. Available at: Accessed 20 June2008
43. Bentley & Thacker op. cit. note 34
44. Bentley and Thacker's subjects were pharmacy students who had greater than average experience with clinical trials, which may have biased the sample in this study. The largest payment tested in either study was $2000, which limits the scope of the findings. Lastly, the studies recorded only hypothetical willingness to participate, which is different in important respects from actual willingness to participate and so challenges the ability of the study to answer the question of whether large payments are actually unduly inducive. Angela Ballantyne has discussed sample bias and study design; challenging the scope of the findings is original to this paper. See Ballantyne, op. cit. note 269
45. Wilkinson & Moore, op. cit. note 24.
46. A. Buchanan &D. Brock. Deciding for Others. Milbank Q198664217 94
47. When arguing against the prohibition on large payments, Ezekiel Emanuel employs a different sliding scale criterion, which might be called a risk/benefit-relative criterion. Using this criterion he argues that a prohibition should be conditional upon IRB approval rather than risk (as I argue here). According to this criterion, even when there is a significant risk of harm, as long as there is a significant possibility for benefit then a lower threshold of competence is appropriate. While an r/b-relative criterion of competence shares the same theoretical foundation as a risk-relative criterion of competence, I argue that the scope of its applicability is more narrow and, in fact, excludes many types of human subjects research. The criteria are similar in that both hold a person's expressed preference should be challenged only when that person faces harm; but they differ in that the risk-relative criterion considers any and all harms, whereas the r/b-relative criterion other considers only unanswered harms. According to the r/b-relative criterion of competence, even if a person experiences some harm during a transaction, there is no need for protection if he experiences a net benefit in the end. While the r/b-relative criterion is appropriate for transactions in which the risks and benefits go hand in hand, it is inappropriate for transactions in which the probability for benefit is not directly related to the probability for risk. That is, when a benefit can occur with or without a harm, and, more importantly, a harm can occur with or without a benefit, then it is possible for a person to conclude a transaction having experienced harm without benefit. In many medical research trials the probability for harm and benefit are not directly related. For example, when testing a promising new intervention a subject could experience any of three possible scenarios: (1) harm without benefit if the drug has side effects but proves to be ineffective; (2) benefit without harm if the drug is effective and has no side effects; or (3) both benefit and harm if the drug is effective but has side effects. Because we can never know in advance which of these scenarios a subject will experience, the r/b-relative criterion of competence is inappropriate for trials of new interventions. See: Emanuel, op. cit. note 24.
48. For more on these concerns see: Weijer. op. cit. note 2; Wilkinson & Moore, op. cit. note 2
49. According to the ISI Web of Knowledge, Dickert and Grady's wage standard has been used in at least 105 articles since 2000. For more see Dickert & Grady, op. cit. note 62000