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Fixing Research Subjects Protection in the United States: Moving Beyond Consent

2013; Elsevier BV; Volume: 88; Issue: 5 Linguagem: Inglês

10.1016/j.mayocp.2013.03.010

1942-5546

Barbara A. Koenig,

Ethics in medical practice

Clinical research requires the active participation of human volunteers in clinical trials of new drugs, devices, or procedures. It is “the foundation on which medical and scientific discoveries…are translated into practice.”1Henderson G.E. Is informed consent broken?.Am J Med Sci. 2011; 342: 267-272Crossref PubMed Scopus (50) Google Scholar Over the past decades, a vast enterprise devoted to the protection of human participants in research has grown up. We all know its basic structure: oversight by institutional review boards that often demand longer and denser consent forms for participants to read and sign (or potentially to ignore). There is widespread agreement that the human subjects protection system in the United States is in need of major restructuring.2Emanuel E.J. Menikoff J. Reforming the regulations governing research with human subjects.N Engl J Med. 2011; 365: 1145-1150Crossref PubMed Scopus (92) Google Scholar Criticism abounds. Investigators are overwhelmed by paperwork; research is slowed down. Inconsistencies and inefficiencies are well known.3Abbott L. Grady C. A systematic review of the empirical literature evaluating IRBs: what we know and what we still need to learn.J Empir Res Hum Res Ethics. 2011; 6: 3-19Crossref PubMed Scopus (186) Google Scholar Universities and academic health centers—terrified by threats of shutdowns by the federal Office of Human Research Protections—intensify efforts to assure paperwork compliance, often through the creation of complex computer systems to track submissions and versions of consent documents. In this issue of Mayo Clinic Proceedings, Yarborough4Yarborough M.A. Increasing enrollment in drug trials: the need for greater transparency about the social value of research in recruitment efforts.Mayo Clin Proc. 2013; 88: 442-445Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar proposes efforts to ameliorate current human research protection procedures, and Chludzinski et al5Chludzinski A. Irani C. Mascha E.J. Kurz A. Devereaux P.J. Sessler D.I. Protocol understanding and anxiety in perioperative clinical trial patients approached for consent on the day of surgery.Mayo Clin Proc. 2013; 88: 446-454Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar contribute to reform by empirically evaluating changes in informed consent practices. Lamenting the political and economic reality of “me-too” drugs and other health care industry efforts that expand profit, patent protection, or market share rather than improving health outcomes, Yarborough proposes requiring the disclosure of the “relative social value” of a clinical trial as part of the initial informed consent process. His disclosure-based reform assumes that individual patients, confronted by information and data, will “just say no” to research that lacks social value, in the same way they might seek to minimize personal risk. Chludzinski et al focus on the informed consent process, historically the linchpin of research subjects protection, reporting the results of a clinical trial of “same-day” informed consent built into an ongoing surgical trial. Study results indicate that, contrary to expectations, patients do not have increased anxiety or decreased understanding when informed consent for research happens immediately before surgery. Although we should applaud the thoughtful efforts of Chludzinski et al5Chludzinski A. Irani C. Mascha E.J. Kurz A. Devereaux P.J. Sessler D.I. Protocol understanding and anxiety in perioperative clinical trial patients approached for consent on the day of surgery.Mayo Clin Proc. 2013; 88: 446-454Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar and Yarborough4Yarborough M.A. Increasing enrollment in drug trials: the need for greater transparency about the social value of research in recruitment efforts.Mayo Clin Proc. 2013; 88: 442-445Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar to improve the conduct of research involving human subjects, we also must note that both articles focus on a single component of human research protection: the informed consent process. In my view, current efforts to reform the conduct of human research rest too heavily on revising the informed consent process and place too much emphasis on disclosure of risk or potential researcher conflict of interest to the human research participant, to the relative exclusion of other equally important—or potentially more important—components of the research approval process. Human subjects protection practices that are built on voluntary participation and consent were constructed on the foundation of celebrated cases of abuse, specifically the Nazi human experimentations reviewed at the Nuremberg Trials and, more recently, the Tuskegee and Guatemala sexually transmitted disease experiments.6Presidential Commission for the Study of Bioethical Issues. Moral science: protecting participants in human subjects research. http://bioethics.gov/cms/sites/default/files/Moral%20Science%20June%202012.pdf. Published December 2011. Updated June 2012. Accessed March 18, 2013.Google Scholar We can easily agree that individuals who are provided with adequate information, and who are free of external coercion, can refuse to participate in research that they deem excessively risky, unduly invasive, or otherwise counter to their interests. Although the creation of today’s standard model of informed consent provided a pragmatic response to these historical abuses, it is inadequate to the complexities of the contemporary research environment. In reaction to the aforementioned iconic cases of breaches in research ethics, the current system was built on theoretical principles—respect for persons, beneficence, and justice—not systematic experimentation and evaluation of actual practice. The emphasis on patient autonomy reflects foundational American values. To those schooled in the traditions of liberal individualism, the notion of empowering prospective research participants to protect themselves, through wise choices following full disclosure of risks and benefits, seems like nothing more than common sense. Indeed, it has become a ritual enshrined in everyday practice7Stark L. Behind Closed Doors: IRBs and the Making of Ethical Research. The University of Chicago Press, Chicago, IL2012Google Scholar and even turned into a verb, “to consent” the patient. Speaking against informed consent as the principal component of human research participant protection seems almost un-American. Nonetheless, a robust critique of informed consent has begun to emerge. Complaints include: too much focus on the form, as opposed to the process, of informing potential research participants; longer, complex, legalistic documents that serve the interest of institutions, not patients; and inconsistent and uneven enforcement of consent standards, both within and among institutions. Empirical studies have demonstrated several serious flaws: participants often see the informed consent process as simply the ritualized entry point into research participation, not an actual choice, and when questioned, subjects’ comprehension of the key components of consent is limited.1Henderson G.E. Is informed consent broken?.Am J Med Sci. 2011; 342: 267-272Crossref PubMed Scopus (50) Google Scholar Indeed, research has demonstrated that significant numbers of participants are unable to recall the main purpose of a clinical trial in spite of signing fully compliant consent documents.8Griffin J.M. Struve J.K. Collins D. Liu A. Nelson D.B. Bloomfield H.E. Long term clinical trials: how much information do participants retain from the informed consent process?.Contemp Clin Trials. 2006; 27: 441-448Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar Recent anthropological research has evaluated the actual process of informed consent in multiple practice settings, including pharmaceutical studies carried out in community-based contract research organizations9Fisher J.A. Medical Research for Hire: The Political Economy of Pharmaceutical Clinical Trials. Rutgers University Press, Hoboken, NJ2009Google Scholar and in international clinical trials.10Petryna A. When Experiments Travel: Clinical Trials and the Global Search for Human Subjects. Princeton University Press, Princeton, NJ2009Crossref Google Scholar These field studies have consistently demonstrated that the informed consent process, in spite of lengthy forms, full disclosure of potential risks, and consistent use, is inadequate to the task of protecting research subjects. Consent simply cannot bear the weight it is asked to shoulder in the current human research participant protection system. Since the publication of the Belmont Report in 1979 (a federal government report that established principles to guide human subjects research),11National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research. US Department of Health and Human Services website. http://www.hhs.gov/ohrp/humansubjects/guidance/belmont.html. Published April 18, 1979. Accessed March 18, 2013.Google Scholar and codification of the Belmont Report into the regulations of the Common Rule, concluded in 1991,12Federal Policy for the Protection of Human Subjects (‘Common Rule’). US Department of Health and Human Services website. http://www.hhs.gov/ohrp/humansubjects/commonrule/index.html. Accessed March 18, 2013.Google Scholar the human subjects protection enterprise has grown considerably, some would say excessively. Efforts at reform were proposed in 2011, when the US Department of Health and Human Services issued an “advance notice of proposed rulemaking” with the intent of seeking comments and eventually modifying—for the first time in decades—practices embodied in the Common Rule.2Emanuel E.J. Menikoff J. Reforming the regulations governing research with human subjects.N Engl J Med. 2011; 365: 1145-1150Crossref PubMed Scopus (92) Google Scholar Reforms in informed consent practice were recommended, including shorter forms and fewer requirements for minimal-risk research. In spite of support from the highest levels of the administration, to date no action has been taken by the Department of Health and Human Services; efforts at reform appear to be stalled, suggesting the magnitude of the policy challenge.13Basken P. Federal overhaul of rules for human research hits impasse. The Chronicle of Higher Education. http://chronicle.com/article/Overhaul-of-Rules-for-Human/137811/. Accessed March 7, 2013.Google Scholar Although I share Yarborough’s desire to make certain that the social utility of research is highlighted as protocols are vetted by research oversight committees,4Yarborough M.A. Increasing enrollment in drug trials: the need for greater transparency about the social value of research in recruitment efforts.Mayo Clin Proc. 2013; 88: 442-445Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar I question whether disclosure to research participants is the answer. The advance notice of proposed rulemaking, which remains tethered to a consent-based human subjects protection paradigm, ignores the politically sensitive topic of social value. Disclosure via consent is unlikely to be the most efficacious way of guaranteeing attention to the common good. If research studies are not carefully designed to ferret out meaningful comparisons of existing therapies with novel techniques or drugs, it seems odd to pin the burden on patient choice, rather than placing the responsibility for such judgments on scientific or clinical review boards. Given our rapidly changing research environment, including the advent of comparative effectiveness research that will force a spotlight on the relative value of novel interventions, what is the answer? Certainly, we need more well-designed studies like that of Chludzinski et al5Chludzinski A. Irani C. Mascha E.J. Kurz A. Devereaux P.J. Sessler D.I. Protocol understanding and anxiety in perioperative clinical trial patients approached for consent on the day of surgery.Mayo Clin Proc. 2013; 88: 446-454Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar that examine the human research participant protection enterprise. I applaud efforts to conduct empirical research interrogating standard informed consent practices. Without such work, we will not find the right way to assure that robust consent has been obtained, when appropriate, or to ascertain the correct “dose” of consent vs other means of respecting research participants. However, as a counterbalance to the intense attention to consent practices, I believe that we need a renewed focus on promoting and enabling authentic ethical reflection as well as a new pathway for embedding patient values and voices into the practice of research. We cannot simply ask individual patients, unaided, to weigh risk levels and evaluate projects by themselves. We must reform a system that valorizes the informed consent process to the exclusion of other elements of human subjects protection. Researchers themselves must be aware of how the political economy of contemporary health care might funnel a less than ethical research proposal into the system’s hopper. Institutional review boards tend to focus on consent forms because they are easy to revise and edit, often at the expense of more substantive concerns. In my view, the focus on forms, process, and tracking in electronic systems has taken attention away from the original intent of the Belmont Report framers. The point was to demand that clinical researchers think carefully, early in the design phase and in advance of starting a study, about the impact of their actions on human participants. And those reflections were never imagined to be solitary, made while sitting in front of a computer entering answers into a database or making certain that the correct template language is included on a consent form. Rather, the idea was to require active discussion with colleagues and peers who were knowledgeable but not invested in the work. Rather than disclosing the potential social value of research to participants, why not change the rules and require institutional review boards to start their review with that question? For such a reform to be successful, we would need to devote as much time and energy to engaging with communities of patients to establish collective priorities for research as we have in writing and rewriting consent forms.