WadeW., “Patient Died During a Trial of Therapy Using Genes,”New York Times, September 29, 1999, at A-24 (describing the death of Jesse Gelsinger); AltmanL.K., “Volunteer in Asthma Study Dies After Inhaling Drug,”New York Times On the Web, June 15, 2001 (describing the death of Ellen Roche), available through <http://www.nytimes.com>.
2.
President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research, Compensating for Research Injuries: The Ethical and Legal Implications of Programs to Redress Injured Subjects, (1982) [hereinafter President's Commission].
3.
Advisory Committee on Human Radiation Experiments, Final Report, (1995).
4.
National Bioethics Advisory Commission, Ethical and Policy Issues In Research Involving Human Participants, (2001) [hereinafter NBAC].
5.
BurmanW.J.RevesR.R.CohnD.L.SchooleyR.T., “Breaking the Camel's Back: Multicenter Trials and Local Institutional Review Boards,”Annals of Internal Medicine, 134 (2001): 152–57, at 152. These authors cite a government report published in 1998 that estimated a 42 percent increase in the number of protocols submitted to local IRBs over the previous 5 years, many of them multicenter trials. Many of these trials are industry-sponsored.
6.
SepkowitzK.A., “AIDS — The First 20 Years,”N. Engl. J. Med, 344 (2001): 1764–72, at 1770. AIDS activism resulting from efforts to participate in clinical trials in order to receive treatment altered drug development in the U.S., including a more efficient FDA review and approval process. Nonetheless, conflicts for patients persist, as the roles of patient and research subject are not mutually exclusive. As detailed in Sepkowitz's chronology of the AIDS epidemic, both incidence and death rates began to fall in the mid-1990s, in large part because of more effective treatment. However, the toxicities of these agents are not trivial; for a catalog of currently available drugs within each class, and their toxicities, see CarrascoD.A.TyringS.K., “Advances in HIV Treatment and Treatment Toxicities,”Dermatology Clinics, 19 (2001): 757–72. Among the more significant side-effects are bone marrow suppression, liver toxicity, neuropathy, pancreatitis, lipodystrophy, and metabolic derangements.
7.
See Wade, supra note 1.
8.
45 C.F.R. § 46.116 (2001) (setting forth the general requirements for informed consent). The requirements relating to injury, addressed in paragraph (a)(6), are for projects with more than minimal risk. These regulations also prohibit use of any exculpatory or “hold harmless” clauses designed to release the investigators or sponsor from liability.
9.
See President's Commission, supra note 2, at 65–80.
10.
See NBAC, supra note 4, at 123–25.
11.
Personal communication from Bonnie Lee, Food and Drug Administration, to author (April 13, 2001).
12.
Personal communication from Bert Spilker, Pharmaceutical Research and Manufacturers of America, to author (March 27, 2001).
13.
CardonP.V.DommelF.W.JrTrumbleR.R., “Injuries to Research Subjects: A Survey of Investigators,”N. Engl. J. Med., 295 (1976): 650–54. Overall, these authors equaled the risk for injury from participation in research to that incurred in everyday life.
14.
Personal communication from Elizabeth Cherry, Office of Risk Management, University of Washington, to author (April 9, 2001).
15.
See President's Commission, supra note 2, at 65–80.
16.
See Cherry, supra, note 14.
17.
ChildressJ.F., “Compensating Injured Research Subjects: 1. The Moral Argument,”The Hastings Center Report, 6 (1976): 21–27. Childress uses the analogy of a “Good Samaritan” in describing this response, which in his view, however, is “not very stringent” from a moral perspective.
18.
See President's Commission, supra note 2, at 49–64.
19.
See NBAC, supra note 4, at 123–26. NBAC notes that medical costs for care of research-related injury should at least be the responsibility of institutions and sponsors who benefit from the research.
20.
VasgirdD.R.HensleighM.BerkmanA., “Protecting the Uninsured Human Research Subject,”Journal of Public Health Management Practice, 6 (2000): 37–47. These authors believe the principles of beneficence and justice espoused by the Belmont Report, National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research (1979), justify amending federal regulations to mandate care for research-related injury.
21.
HopeT., “Compensating Subjects of Medical Research,”Journal of Medical Ethics, 23 (1997): 131–32.
22.
See id. (editorial questioning whether completing consent doesn't waive rights for compensation). Hope uses, as an example, an individual who is responding to need, but who incurs personal injury; such action does not automatically warrant compensation so why should participation in research, where the individual receives disclosure about risks and yet volunteers to take part?.
23.
See Childress, supra note 17. The three features noted in the text are, briefly, the existence of positional risk, benefit to society, and society's sponsorship or mandate.
24.
See Vasgird, supra note 20.
25.
38 C.F.R. § 17.85 (2000). A VA Research Consent Form would include the following language (or a variation thereof): “If you sustain physical injury as a direct result of your study participation, medical care will be provided by (local facility) at no cost to you. Financial compensation for such things as lost wages, disability, or discomfort due to injury is not available.”
26.
Personal communication from James F. Burris, Office of Research and Development, Department of Veterans Affairs, to author (March 28, 2001).
27.
Health Care Financing Administration, Program Memorandum Intermediaries/Carriers: Claims Processing Instructions for Carriers, DMERCS, Intermediaries and Regional Home Health Intermediaries (RHHIs) for Claims Submitted for Medicare Beneficiaries Participating in Medicare Qualifying Trials, at <http://cms.hhs.gov/manuals/pm_trans/AB0089pdf> (last visited June 6, 2003).
Because of this retroactive coverage, it is conceivable that a vaccine might have been under development (i.e. in clinical trial) when injury occurred.
30.
Personal communication from Geoffrey Evans, National Vaccine Injury Compensation Program, to author (April 4, 2001).
31.
See Cherry, supra note 14; see also University of Washington, Human Subjects Division: General Information Archive, at <http://depts.washington.edu/hsd/info.htm> (last visited May 23, 2003).
32.
Wake Forest University School of Medicine has, effective September 1, 2001, initiated a policy based on the assumption that for research of greater than minimal risk, “… provisions must be made for the coverage of reasonable costs for the necessary treatment for illnesses, adverse events or injuries that results from medications, devices, interventions, procedures, or tests that the research study subject would not have been exposed to had he or she not volunteered to participate. …” The policy mandates that this be included in the research agreement when industry sponsors the research, but limits responsibility to expenses not paid by any existing third party coverage. A liability policy, at the time underwritten by the St. Paul Insurance Company, would provide coverage up to $25,000 for studies sponsored by NIH, other non-profit sponsors, or the institution. See Research Related Injury Policy and Procedure, available at <http://www.wfubmc.edu/or/irbpol.html> (last visited June 11, 2003).
33.
See Cherry, supra note 14.
34.
Personal communication from Tena Lummus, Department of Human Resources, University of Texas System, to author (April 9, 2001). See also 45 C.F.R. § 46.116, supra note 8. A waiver of liability is clearly prohibited, returning responsibility to the sponsor.
35.
See President's Commission, supra note 2, at 65–80.
36.
See Spilker, supra, note 12.
37.
Personal communication from Robert Lee, Evanston Insurance Company, Chicago, IL, to author (April 18, 2001).
Associated Press, “Penn Settles Suit on Genetic Test,”New York Times, November 4, 2000, at A-18 (describing the resolution of the Jesse Gelsinger case discussed in supra note 1).
41.
See Vasgird, supra note 20. The authors cite evidence that”… a growing number of research subjects in high-risk studies are drawn from lower socioeconomic status (SES) groups. …” This is presumably because of financial incentives and access to a health-care system not otherwise available to low-income individuals. Such individuals are less likely to be knowledgeable about legal processes and often lack the financial resources to effectively use them. Civil action, even if successful, does not provide prompt payment, which is an additional problem for individuals with limited means.
42.
See President's Commission, supra note 2.
43.
See 45 CFR § 46.116, supra note 8.
44.
MorinK.M.RakatanskyH.RiccickF.A.Jr., “Managing Conflicts of Interest in the Conduct of Clinical Trials,”JAMA, 287 (2002): 78–84.
45.
BartonJ.M.MacmillanM.S.SawyerL., “The Compensation of Patients Injured in Clinical Trials,”Journal of Medical Ethics, 21(1995): 166–69. (summarizing the ABPI policy). Coverage is provided for “… bodily injury (including death) …” and “… should be paid when, on the balance of probabilities, the injury was attributable to the administration of a medicinal product under trial or any clinical intervention or procedure provided for by the protocol …” that was part of the research. The payment “… should be appropriate to the nature, severity and persistence of the injury …” in an amount that might be court awarded for a similar injury “… in cases where legal liability is admitted.”
46.
GuestS., “Compensation for Subjects of Medical Research: The Moral Rights of Patients and the Power of Research Ethics Committees,”Journal of Medical Ethics, 32 (1997): 181–85.
47.
BrodyB.A., The Ethics of Biomedical Research: An International Perspective (New York: Oxford University Press, 1998): At 52–53 and appendices 1.8 (section 13), 2.2 (principle 14), and 4.1 (§§ 58–60).
48.
See President's Commission, supra note 2, at 113–49.
49.
See NBAC, supra note 4. In its initial draft of this report on research oversight, which was made available for public comment at the end of 2000, NBAC recommended that Congress create an administrative system to compensate insured participants for medical and rehabilitation costs, while gathering much needed data on frequency. There was no mention of coverage of economic losses. The program would have functioned as a social insurance plan. Thus, NBAC concluded originally that action was necessary and felt comfortable in making a commitment; apparently comment tempered this enthusiasm and in the final report, as noted earlier, NBAC simply endorsed the President's Commission proposal.
50.
A universal health-care system in which all participate has appeal in the research setting because it fulfills the criterion of responding to medical need, regardless of the setting in which injury was incurred. Moreover, it would eliminate the conflict for the uninsured created when the individual's primary motivation for participation in research may be access, not otherwise available, to the health-care system. It would also signal a new era in health-care justice in the United States, one that would likely encompass sharing in the burdens as well as the benefits of clinical research. It would not, however, address economic losses, should they occur.
51.
Ken Greisman of TAP Pharmaceuticals responded to this question by noting that it is the policy of his company to pay for care if a subject taking part in an investigational trial is injured. Personal communication from Ken Greisman to author (April 20, 2001).
52.
JuengstE.WaltersL., “Ethical Issues in Human Gene Transfer Research,” in FriedmanT., ed., The Development of Human Gene Therapy (Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, 1999): 691–712.
53.
An example is a clinical trial involving surgery in which the control group receives a sham operation. But is the IRB justified in raising the standard for research protocols like this? Federal regulations set minimum standards and do not specifically authorize IRBs to raise them. Nonetheless, there are no limits or restrictions set on the role of IRBs in assuring participant safety and welfare. As a result, the level of protection necessarily increases as risk increases and more so if there is no offsetting benefit. Respect for individuals and beneficence, two of the three guiding principles of the Belmont Report, obligate the research community to assure that these protections are in place when circumstances require them.
54.
Given the burden of responsibility and work already shouldered by IRBs, it could easily be argued that expecting them to develop expertise in options for injury compensation is unrealistic. Risk assessment, however, is already an IRB function. For studies in which there is concern regarding risk and injury, resources could be developed that would be generally accessible not only to IRBs, but investigators as well. An example might be guidance material developed by Office for Human Research Protections, which provides this information and contains examples of studies for which injury compensation should be considered and available options appropriate for that study.
55.
Institute of Medicine, “Preserving Public Trust: Accreditation and Human Research Participant Protection Programs, (2001). In this report, “… a broader system with multiple functional elements …” was envisioned, including research sponsors and organizations, the IRB, investigators, monitoring bodies, and the participants themselves.
