The case for evidence-based rulemaking in human subjects research

American Journal of Bioethics

Volumn 10, Issue 6, 2010, Pages 3-13

  Sachs, Benjamin ^a  

^a NEW YORK UNIVERSITY   (United States)

Author keywords

Belmont report; Declaration of helsinki; Nuremberg code; Research ethics; Rules

Indexed keywords

ARTICLE; CLINICAL TRIAL; DECISION MAKING; ECONOMICS; ETHICS; EVIDENCE BASED MEDICINE; HEALTH CARE DELIVERY; HEALTH CARE POLICY; HIGH RISK BEHAVIOR; HUMAN; HUMAN EXPERIMENT; HUMAN RELATION; INFORMED CONSENT; MANAGEMENT; MEDICAL ETHICS; METHODOLOGY; NOMENCLATURE; PATIENT; PATIENT RIGHT; PERSUASIVE COMMUNICATION; PRACTICE GUIDELINE; RESEARCH ETHICS; RESEARCH SUBJECT; SALARY AND FRINGE BENEFIT; STANDARD; UNITED STATES;

CHOICE BEHAVIOR; CLINICAL TRIALS AS TOPIC; CODES OF ETHICS; COERCION; ETHICS; ETHICS, RESEARCH; EVIDENCE-BASED MEDICINE; HEALTH POLICY; HEALTH SERVICES ACCESSIBILITY; HELSINKI DECLARATION; HUMAN EXPERIMENTATION; HUMANS; INFORMED CONSENT; PATIENT DROPOUTS; PATIENT RIGHTS; POLICY MAKING; PRACTICE GUIDELINES AS TOPIC; RESEARCH DESIGN; RESEARCH SUBJECTS; RESEARCHER-SUBJECT RELATIONS; RISK-TAKING; SALARIES AND FRINGE BENEFITS; TERMINOLOGY AS TOPIC; UNITED STATES;

EID: 77953404988     PISSN: 15265161     EISSN: 15360075     Source Type: Journal    
DOI: 10.1080/15265161003702857     Document Type: Article

References (47)

1. http://ohsr.od.nih.gov/guidelines/nuremberg.html
2. Policy of the World Medical Association. 2008 version. http://www.wma.net/e/policy/b3.htm.
3. Issued by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. http:// ohsr.od.nih.gov/guidelines/belmont.html.
4. Issued by the Council for International Organizations of Medical Sciences. 2002 version. http://www.cioms.ch/frame guidelines nov 2002.htm.
5. Issued by the National Bioethics Advisory Commission. Bethesda, MD. 2001. http://www.bioethics.gov/reports/past commissions/nbac international.pdf
6. Revised edition. Harper Perennial, 2001. Address correspondence to Benjamin Sachs, New York University, Environmental Studies and Bioethics, 285 Mercer 9th Floor, New York, NY, 10003, USA. E-mail: sachs@nyu.edu
7. Frederick Schauer, Playing by the Rules (Oxford: Clarendon Press, 1991), p. 129.
8. Frederick Schauer, Playing by the Rules, p. 112.
9. This is identical to the oft-made distinction between ethical rules and laws. It makes sense that the two distinctions should be drawn in the same way, since laws are policies.
10. I thank Margaret Little for this example. For this kind of argument against legalizing physician-assisted suicide, see Ezekiel J. Emanuel, "What is the great benefit of legalizing euthanasia or physician-assisted suicide?," Ethics 109 (April 1999): 629-642.
11. Schauersays that they create reasons (Playing by the Rules, pp. 5-6,51-52), and I agree. I simply want to say that they create reasons by way of creating obligations.
12. Schauer, Playing by the Rules, p. 53.
13. Trials of War Criminals before the Nuremberg Military Tribunals underControlCouncilLawNo.10.Nuremberg,October1946-April1949 (Washington, DC: U.S. Government Printing Office, 1949-1953).
14. In fact the Belmont Report explicitly states which ethical principles are supposed to justify its rules.
15. Benjamin Sachs, "Going from principles to rules in research ethics," forthcoming in Bioethics. Early view available at http://www3.interscience.wiley.com/cgi-bin/fulltext/122525565/pdfstart.
16. Benjamin Sachs, "The exceptional ethics of the investigatorsubjectrelationship,"JournalofMedicineandPhilosophy 35(1)(February 2010): 64-80.
17. Rule-based obligations, or the reasons they ground, can range from weak to absolute (Schauer, Playing by the Rules, pp. 113-118). My arguments are intended to be effective no matter how strong the obligations are purported to be.
18. For an example of a defense of Responsiveness motivated in this way, see Alex John London, "Responsiveness to host community health needs," in Ezekiel J. Emanuel et al., eds., The Oxford Textbook ofClinicalResearchEthics(NewYork:OxfordUniversityPress,2008), pp. 737-744.
19. Characteristic instances of this argument are found in NBAC (Chapter 4)and CIOMS (GeneralEthical Principles-Justice).Other examples include Leonard H. Glantz, George J. Annas, Michael A. Grodin, and Wendy K. Mariner, "Research in developing countries: Taking 'benefit' seriously," Hastings Center Report 28(6) (1998): 38-42, reprinted in Bonnie Steinbock, Alex John London, and John D. Arras, eds., Ethical Issues in Modern Medicine, 6th ed. (New York: McGraw-Hill, 2003), pp. 781-786.
20. George J. Annas and Michael A. Grodin, "Human rights and maternal-fetal HIV transmission prevention trials in Africa," American Journal of Public Health 88 (1998): 560-563.
21. Ruth Macklin, Double Standards in Medical Research in Developing Countries (Cambridge: Cambridge University Press, 2004), chap. 4.
22. At this point, one might begin to doubt whether the process of defendingaruleasapolicyrecommendationreallydoesdifferfrom the process of defending it as an ethical rule. It may seem that in seeking a list of rules for the sake of promoting the interests of those affected by them, we are seeking the ethical rules that would fall out of a particular normative ethical theory-rule-utilitarianism. But this impression would be mistaken. While both rule-utilitarians and policy-creators are in the business of promulgating the optimal set of rules, only rule-utilitarians say that those rules would be obligatory even if no one had ever promulgated them21. It is entirely possible that we should hold these candidate policies to a higher standard: that we should demand more of human subjects research policy than its effective promotion of a legitimate goal. Even so, it is worthwhile to inquire whether the recommendations at hand pass even this one test.
23. Alvan R. Feinstein and Jeffrey L. Lichtenstein, "Medical ethics andthearchitectureofclinicalresearch,"AppendixtoBelmontReport, Vol. I (Washington, DC: U.S. Government Printing Office, 1978, DHEW Publication No. (OS) 78-0013), Part 9, pp. 34-35.
24. As Robert J. Levine points out in his Ethics and Regulation of Clinical Research, 2nd ed. (New Haven, CT: Yale University Press, 1986), p. 20.
25. Ezekiel Emanuel, David Wendler, and Christine Grady, "What makes clinical research ethical?," Journal of the American Medical Association 283(20): 2701-2711 at 2704
26. Benjamin Freedman, "Scientific value and validity as ethical requirements for research: A proposed explication," IRB (November/December 1987): 7-10 at 7.
27. This is consistent with the claim that there is both a lower and an upper limit to how (in)valid a study can be.
28. Christine Grady,"The challenge ofassuring continued post-trial access to beneficial treatment," Yale Journal of Health Policy, Law, and Ethics 1 (2005): 425-435.
29. Ruth Macklin, "'Due' and 'undue' inducements: On paying money to research subjects," IRB 3(5) (May 1981): 1-5 at 4-5.
30. Terrence F. Ackerman, "An ethical framework for the practice of paying research subjects," IRB 11(4) (July/August 1989): 1-4 at 2
31. Marx Wartofsky, "On doing it for money," in National Commission for the Protection of Human Subjects, Research Involving Prisoners: Report and Recommendations, Appendix, DHEW Publication No. (OS) 76-132 (Washington, DC, 1976), chap. 3 at 3-21.
32. Robert J. Levine, Ethics and Regulation of Clinical Research, 2nd ed. (New Haven, CT: Yale University Press, 1986), p. 83
33. Paul McNeill, "Paying people to participate in research: Why not?," Bioethics 11(5) (1997): 390-396 at 394.
34. This point was originally made by Joel Feinberg, "Noncomparative justice," Philosophical Review 83(3) (July 1974): 297-338, and is now widely accepted among political theorists and moral philosophers.
35. Rebecca Wolitz, Ezekiel Emanuel, and Seema Shah, "Rethinking the responsiveness requirement for international research," Lancet 374(9692): 847-849.
36. Nuffield Council on Bioethics, The Ethics of Research Related to Healthcare in Developing Countries (London: 2002), p. 19. 31. This undermines NBAC's point that it is irrelevant if Reasonable Availability deters the carrying out of studies since studies that don't abide by Reasonable Availability are of no benefit to host communities anyway (NBAC, p. 68).
37. This has not stopped some commentators from stating that imposing the Reasonable Availability rule will work to the benefit of citizens of developing countries. See, for instance, Peter Lurie and Sidney M. Wolfe, "The developing world as the 'answer' to the dreams of pharmaceutical companies: The Surfaxin story," in James V. Lavery et al., eds., Ethical Issues in International Biomedical Research: A Casebook (New York: Oxford University Press, 2007), pp. 159-170 at 166.
38. Schauer, Playing by the Rules, chap. 3 and pp. 100 and 135. 34. Ibid., pp. 83-84.
39. Strictly speaking, "no rule at all" isn't really an option. Empowering IRBs to make decisions about certain matters requires putting in place jurisdictional rules, which are quite different from the rules we have been discussing but are rules nonetheless. See Schauer, Playing by the Rules, pp. 167-174.
40. In order to know whether skepticism is called for, we should monitor IRBs' attempts to exercise good judgment on the matters about which they currently do exercise their judgment. We might study whether IRBs do a good job of making these determinations. If we had data on this, and if we reached some conclusions about how we might extrapolate our findings to the question of how well IRBs could be expected to exercise their judgment on the matters covered by the seven rules, then, and only then, could we be justified in saying that there should or should not be policies regarding matters such as scientific validity, post-trial access, and responsiveness. Alternatively, we might study the question prospectively, allowinga handful ofIRBs tomake determinationsonthese matters on a probationary basis and then reviewing the results.
41. Schauer, Playing by the Rules, chap. 7. For some doubts about this, see ibid., pp. 136-137.
42. Should the rulemakers grant such status? This is a difficult question to which I cannot do justice here, but my inclination is to say that it depends on the rule: If part of the point of the rule is to confer a benefit on subjects or community members, then yes. When such rules are broken, it makes sense that subjects or community members should be granted the standing to demand some compensation for not having received the benefit that conformity to the rule would have conferred on them.
43. Declaration of Helsinki, Principles 10 and 15.
44. Thus, I am not proposing that all ethical language be removed from the pronouncements.
45. Baruch Brody, The Ethics of Biomedical Research (Oxford: Oxford University Press, 1998), pp. 198-199.
46. This way of conceiving of the problem was suggested to me as I read Cass Sunstein's book Worst-Case Scenarios (Cambridge, MA: Harvard University Press, 2007).
47. What kind of research should we undertake? If we are really ambitious we might want to undertake prospective trials in which researchers and their protocols are randomized to IRBs enforcing differing sets of rules. To carry this out, however, we would have to allow the rules to be broken; this might be unpalatable to the research community. In any event, it's not clear to me that all the other variables could be silenced. A more feasible, albeit less satisfying, kind of research would be a set of surveys aiming to solicit from investigators, potential subjects, and community members information regarding how they would behave if the rules were different.