Protection of Human Subjects and Scientific Progress: Can the Two Be Reconciled?

Abstract

To the Editor: Over the past several years, both the professional and lay press have made distressing revelations concerning the enterprise, including financial conflicts of interest involving investigators, NIH managers, and FDA regulatory procedures; insufficient disclosure of risks; lack of transparency regarding investigators' commercial ties; ghost writing of clinical trial manuscripts by sponsors; failure to publish negative trial results; trials designed to conceal serious drug side effects; failure to systematically assess what is known from existing before launching new studies; and inadequacies in the ethics review process, including IRB members' level of preparation and the monitoring of ongoing research. Ironically, these revelations coincide with a rising chorus within the ethics community that advocates relaxing certain well-established norms and values aimed at protecting subjects. A troubling thread runs through much of the recent literature, both that appearing in the Hastings Center Report on changing standards of research and elsewhere. The key ethics question has moved from How can we balance subject protection with the acquisition of knowledge? to How can we facilitate I believe this emphasis on tolerating higher levels of risk erodes protections traditionally provided by ethical protocol design and voluntary and informed consent procedures. Much of this discourse presumes a great deal, including that some subject protections stand in the way of significant scientific advancement. It also assumes that most is good, or necessary, or important; that all IRBs are competent to assess the risk/benefit balance with surgical precision or that they always know how much risk should be allowed when the benefit is exclusively to future patients; and that bad deal or exploitative trials somehow become acceptable, as opposed to doubly unacceptable, with mandatory random assignment to participate. Certain authors assume that distinguishing between and therapy somehow provides a morally and legally legitimate rationale for weakening physicians' obligations to patients who are subjects, or that failure to demand relevant comparison trials (instead of promoting placebo controlled trials) will not disadvantage future patients looking for effective medication. Should we assume that patients presented with mandatory participation in trials of two approved agents won't see this as a breach of trust by their physicians? That seeing one is as good as seeing another, or that alternative physicians acceptable to patients are always and everywhere available? Some authors assume that once trials of new agents are approved by an IRB, coercion is irrelevant, as they are a reasonable choice for all eligible participants; that mentally competent adults who are ill or poor or without adequate social supports are not subject to pressures that inhibit the kind of voluntary choice we ought to insist upon; or that paying subjects will not result in an underclass populated by those in temporary or permanent need of money. If facilitating is the real objective, why not place more emphasis on important issues such as improved education for IRB members and trainees; better administrative support for IRBs; coordination of multicentered clinical trial review; requirements for trial registration and data sharing; improved guidance on with children and the sick and dying; advice for health and social science re searchers for value-laden areas such as racism, sexuality, drugs, or stigma; or the myriad of difficulties surrounding uncertainty and risk in the translation of novel cell from bench to bedside? Why aren't there more calls from the ethics community for scientific rigor in research, or more debates on social versus scientific benefits of research? Scientific advancement is a worthy objective, one that can benefit many. …