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In a widely influential article, Emanuel, et al., have identified seven commonly accepted principles that make clinical research ethical: (1) informed consent; (2) a favorable risk/benefit ratio; (3) fair subject selection; (4) scientific or social value; (5) scientific validity; (6) independent review; and (7) respect for enrolled research participants. Emanuel, E. J. Wendler, D., and Grady, C., “What Makes Clinical Research Ethical?” JAMA 283, no. 20 (2000): 2701–2711.CrossRefGoogle Scholar

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45 C.F.R. § 46.111(a)(1) (1991). None of this, of course, is news to anyone familiar with the conduct or regulation of clinical research. It may, however, surprise much of the lay public, especially as influenced by media outlets (including health care advertising) and even patient advocacy groups that portray enrollment in clinical trials as a means to access innovative and curative therapies.Google Scholar

See Menikoff, and Richards, , supra note 21, at 62. While not explicitly required by the Common Rule (45 C.F.R. Part 46) or any other regulations governing research, “clinical equipoise” is a commonly accepted ethical requirement in almost all clinical research (excepting, perhaps “low-risk” studies).Google Scholar

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Id., at 62–63. Deborah Hellman further explains that the concept of equipoise cannot justify the randomized clinical trial because the concept is directed at the question, what should I (the physician) believe? rather than what should I (the patient) do? Hellman, D., “Evidence, Belief, and Action: The Failure of Equipoise to Resolve the Ethical Tension in the Randomized Clinical Trial,” Journal of Law, Medicine & Ethics 30, no. 3 (2002): 375–380.CrossRefGoogle Scholar

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And they are ill-suited to do so, see Bankert, E. and Amdur, R., “The IRB Is Not a Data and Safety Monitoring Board,” IRB: Ethics and Human Research 22, no. 6 (2000): 9–11.CrossRefGoogle Scholar

These were originally (and often still are) called data and safety monitoring boards. We have adopted the broader term data monitoring committees here because that is the term used in current regulation.Google Scholar

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The National Center for Clinical Research Resources at NIH was responsible for rules regarding RSA use. Those rules were withdrawn when the NIH disbanded its CRC program and replaced it with the CTSA program. The CTSA program continues the use of RSAs but the parameters of RSA use are still being debated. See discussion at <https://www.ctsacentral.org/sites/default/files/documents/05031015AMReiderRSA.pdf> (last visited December 14, 2012).+(last+visited+December+14,+2012).>Google Scholar

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As Sandra Johnson has written, “[T]ell doctors that they have a ‘conflict of interest’ in relation to a proposed protocol for research with human subjects, and they believe that you have accused them of unethical behavior….[D]octors tend to assume that a conflict of interest exists only when they actually have made a ‘bad’ decision motivated by their financial interest in the sponsor of the research.” The medical profession in general tends to prefer calling Conflicts between primary obligations, such as medical care and research, “conflicts of obligation.” Id. See Institute of Medicine, Report on Conflict of Interest in Medical Research, Education, and Practice (2009), at 48. In fact, rather than describing medical practice and research as posing conflicting interests, the Report combines these two aims under the “goals of medicine” Id., at 44.Google Scholar

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Model Rule 1.8(h). Not all states have adopted Model Rule 1.8(h) in this form, and some are more restrictive in what they permit. A few states go so far as to proscribe all agreements that prospectively limit a lawyer's liability. See, e.g., New York Rules of Professional Conduct 1.8(h); Alabama Rules of Professional Conduct 1.8(h). New Jersey allows such agreements, but only when “the client fails to act in accordance with the lawyer's advice or refuses to permit the lawyer to act in accordance with the lawyer's advice.” New Jersey Rules of Professional Conduct 1.8(h). According to the Comments to the Model Rules, this independent lawyer requirement is imposed “because [such agreements] are likely to undermine competent and diligent representation.” Thus, there is a recognition and concern that the quality of the representation may be altered (like the “adviser's” advice in the psychological experiments about estimation, discussed above), not merely that the client will be unduly influenced into signing the waiver or misunderstand its import, although those, too, are a concern.Google Scholar

The analogy between the lawyer seeking to limit liability and the physician performing clinical research is not perfect. For one, the legal client is waiving the right to sue for negligence of the lawyer, but the physician-researcher could still be sued for negligence by the patient-subject, however that might be defined. In fact, researchers are prohibited by law from seeking waivers of liability for negligence. 45 C.F.R. § 46.116 (1994); 21 C.F.R. § 50.20 (1995) (prohibiting exculpatory agreements concerning negligence in clinical investigations regulated by the FDA); Vodopest v. MacGregor, 128 Wash. 2d 840, 913 P.2d 779 (1996) (preinjury agreement releasing medical researcher for liability for negligence conduct violates public policy). The point, however, is that almost certainly negligence on the part of the physician-researcher will not be judged in reference to a standard of care that requires exclusive pursuit of the best medical interests of the patient-subject. Second, the lawyer who obtains a waiver of liability from a client has not actually become subject to a different standard of care, but simply cannot be sued by that client for certain deviations from the ordinary standard of care. Others, including professional bar associations, can still hold the lawyer accountable for practicing law to the usual standards of competence and diligence. The point, though, is that this client cannot hold the lawyer legally accountable to such standards and therefore is entitled to another lawyer's guidance on the liability waiver.Google Scholar

The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Pub. No. 78-0012, The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research (1979), available at <http://www.hhs.gov/ohrp/humansubjects/guidance/belmont.html> (last visited December 12, 2012).+(last+visited+December+12,+2012).>Google Scholar

“Beneficence” is used in the Report to describe both negative obligations to do no harm and positive obligations to help others.Google Scholar

The Report appears to conflate the two conceptions of beneficence that physician-researchers might promote – the good for society and the good for individual subject-patients by telling us that “avoiding harm [presumably to individual patients] requires learning what is harmful [by doing research],” and although “the Hippocratic Oath requires physicians to benefit their patients ‘according to their best judgment’” (again, a patient-centered approach), “[l]earning what will in fact benefit may require exposing persons to risk” (research subjects).Google Scholar

Kolata, G. and Eichenwald, K., “Stopgap Medicine: A Special Report; For the Uninsured, Drug Trials Are Health Care,” New York Times, June 22, 1999.Google Scholar

As we are hopeful that eventually everyone in the United States will be insured for health care services, questions relating to the application of our proposal to the person seeking free medical care through research participation may be a temporary one. Unfortunately, however, even optimistic projections of current health care reform demonstrate that there will be a segment of the population still uninsured. Much of that group will truly be part of a vulnerable population. They are likely to be less well educated and many teetering on the edge of financial disaster. Some of them will be undocumented immigrants. This is even greater reason to give them additional support.Google Scholar

This list is based on the broad literature involving human subject protections. But some particulars come from the literature on DMCs which attempt, we believe unsuccessfully, to address some of these concerns. Haavi Morreim's work on patient advocates, supra note 105, was particularly helpful.Google Scholar

In using the word “vulnerable,” we intend to use it more broadly than the definition provided in the current regulations.Google Scholar

See Emanuel, and Emanuel, , supra note 28.Google Scholar

Chen, D. T. Miller, F. G., and Rosenstein, D. L., “Clinical Research and the Physician-Patient Relationship,” Annals of Internal Medicine 138, no. 8 (2003): 669–672 (describing physicians’ role in advising their patients who are considering volunteering for clinical research).CrossRefGoogle Scholar

Chen, D. T. and Shepherd, L. L., “Advising Patients about Obtaining Genomic Profiles,” Neurology Clinical Practice 1, no. 1 (2011): 5–12.CrossRefGoogle Scholar

See Chen, et al., supra note 137.Google Scholar

See Wilson, , supra note 103, at 229–30.Google Scholar

See, e.g., Employers’ Fire Ins. Co. v. Beals, 240 A.2d 397, 400 (R.I. 1968), overruled in part on other grounds, Peerless Ins. Co. v. Viegas, 667 A.2d 785 (R.I. 1995).Google Scholar

Fewer than 2% of adult cancer patients participate in clinical trials. Murthy, V. et al., “Participation in Cancer Clinical Trials,” JAMA 291, no. 8 (2004): 2720–2726.CrossRefGoogle Scholar

There are some reports that some oncologists do not tell their patients about available clinical trials because they would lose them as patients. Klabunde, C. N. et al., “A Population-Based Assessment of Specialty Physician Involvement in Cancer Clinical Trials,” Journal of National Cancer Institute 103, no. 5 (2011): 384–397.CrossRefGoogle Scholar

See, e.g., Comis, R. L. Miller, J. D. Aldige, C. R. Krebs, L., and Stoval, E., “Public Attitudes towards Participation in Cancer Clinical Trials,” Journal of Clinical Oncology 21, no. 5 (2003): 830–835, available at <http://www.harrisinteractive.com/news/allnewsbydate.asp?NewsID=941> (last visited December 6, 2012).CrossRefGoogle Scholar

Ford, F. G. Howerton, M. W., and Bolen, S. et al., Information on Recruitment of Underrepresented Populations to Cancer Clinical Trials. Evidence Report/Technology Assessment No. 122 AHRQ Publication No. 05-E019–2, Agency for Healthcare Research and Quality (June 2005), Rockville, MD; Kennedy, B. R. et al., “African Americans and their Distrust of the Health Care System: Healthcare for Diverse Populations,” Journal of Cultural Diversity 14, no. 2 (2007): 56–60.Google Scholar

In fact, experience with RSAs in studies involving minority populations has demonstrated that having a patient advocate can improve trust in the research and thus recruitment. See Easa, et al., supra note 110, at 3.Google Scholar