Subject Protection Issues Gain Broad Support

The need for special protections for vulnerable populations participating in clinical studies has generated controversy and uncertainty as policy makers and research advocates seek to prevent abuses while also permitting needed studies. A recent report from the Institute of Medicine (IOM) lays out important safeguards for all prisoners participating in clinical studies. Calling for extended federal regulation of all research involving prisoners, however, opens the door to broader legislation expanding standards and oversight procedures for human subject research overall.

Jill Wechsler

Forty years ago, prisoners were widely used in clinical studies, including drug and vaccine trials. That ended in the 1970s when revelations surfaced about paying prisoners to participate in testing, some involving exposure to toxic treatments. This led to the development of stricter policies under Subpart C (research on prisoners) of the "Common Rule," which governs all research funded by or monitored by federal agencies. Today most research involving prisoners is behavioral or epidemiological and has to provide direct benefit to study participants; few prisoners participate in studies sponsored by pharma companies, which largely have taken trials offshore.

Even so, most media reports on the IOM study recalled past abuses and painted the report as re-opening the door to prisoner exploitation, spurred by industry's mounting demand for warm bodies to populate mushrooming clinical studies. Such comments testify to continued low public regard for the human research enterprise and for the ability of public review boards and government agencies to monitor research activity and prevent abuses. A New York Times editorial (Aug. 23, 2006) did take a broader view by recognizing that prisoner testing could benefit inmates as well as the general population—if "carried out carefully" with more federal oversight.

Establishing safeguards

In fact, the IOM report on "Ethical Considerations for Research Involving Prisoners" [available at www.nap.edu] outlines a program to provide more comprehensive safeguards and oversight measures for studies involving prisoners with an eye to improving participant well-being. The aim is to assist the Office of Human Research Policy (OHRP) in the Department of Health and Human Services (HHS) in clarifying ethical and legal issues related to vulnerable research populations. The OHRP, with input from the Secretary's Advisory Committee on Human Research Protections (SACHRP), has been examining options for updating policies governing prisoners, as well as children, the elderly, mentally impaired, and other groups that may lack the resources and independence to objectively evaluate the risks and benefits of participating in a research study.

New Approach to AE Reporting

Broader concern about prisoner research policies emerged after OHRP issued guidance in 2003 calling on sponsors to seek institutional review board (IRB) rereview of a protocol if an individual becomes incarcerated while participating in a clinical trial. Opposition to this approach from SACHRP members and IRB confusion pointed to the need for a wider review of the "ethical underpinnings" of research involving prisoners, explains OHRP Director Bernard Schwetz. The SACHRP said we need "more than band-aids to fix Subpart C."

The IOM report suggests that prisoners could benefit from participation in some Phase III clinical trials, so long as study protocols are fully reviewed and monitored by IRBs and that at least half the subjects are noninmates. The committee is "not necessarily encouraging more research involving prisoners," explains Schwetz, but wants to ensure that proper oversight is in place for those studies that could benefit prisoners.

Broader standards

The report emphasizes the importance of ensuring voluntary informed consent, adequate standards of care, and privacy protection for prisoners. It also calls for establishing a collaborative review approach with input from prisoners on protocol design and expanding the definition of "prisoner" to include restricted individuals in community settings, as well as those incarcerated.

The report also acknowledges that much research involving prisoners now takes place outside current federal regulations, which do not extend to the Department of Justice's Bureau of Prisons or to state prison authorities. To remedy this situation, the panel calls on Congress to establish uniform guidelines and a national oversight system for all human research programs that enroll prisoners.

In discussing the IOM report at its August 1, 2006, meeting, SACHRP went further and proposed that legislation setting standards for prisoners should extend to all human subject research, including independently funded studies that fall outside the boundaries of the Common Rule. SACHRP plans to further discuss strategies for bringing all research under the federal umbrella at its next meeting in November.

Database tracking

Even without legislation, many of the IOM proposals related to studies on prisoners may affect clinical research policies more broadly. A key recommendation is to establish a detailed public database to track all studies involving prisoners and to ensure that such research programs are open, transparent, and accountable. The poor record of pharmaceutical companies in registering active studies on the Clinicaltrials.gov Web site currently is a hot topic in the legislative arena, and support for a prisoner research database could weigh in on the broader debate.

Assessing risk

Another important IOM proposal is to shift to a risk–benefit framework and away from today's category-based model for evaluating research proposals for prisoners. Current rules permit prisoners to enroll only in studies on the effects of incarceration, on health conditions specifically affecting prisoners, and other narrow areas. Instead of checking that a study fits a set category, the IOM panel believes it is more appropriate for researchers and IRBs to weigh the potential harms and benefits of each specific research proposal based on the level of risk, benefit to the individual, and potential knowledge gained.

Such a risk-based approach reflects current thinking that with proper safeguards, prisoners could participate in studies with greater than minimal risk, provided there is potential benefit to the individual. This and other issues similarly arise in OHRP deliberations on policies governing research with children. A SACHRP working group has long been examining topics related to appropriate research involving young patients: privacy protection, the need for special advocates on IRBs, whether young patients have the capacity to give informed consent, and appropriate compensation for trial participants—all relevant also for research with prisoners. Another SACHRP working group seeks to define what makes an individual or population "vulnerable," what are adequate safeguards, and what issues might interfere with informed consent.

Influencing change

Although it would take years for Congress to agree on any legislation expanding standards for human subject research, the IOM report may have a more immediate impact. At a minimum, IRBs and members of the research community will read it and become more aware of the issues and requirements for research involving prisoners. And it may prompt a new look at how the federal government should manage these issues. Broader federal oversight of biomedical research also would expand the scope of OHRP's responsibilities and raise the issue of establishing a federal agency outside of HHS to oversee these issues.

Jill Wechsler is the Washington editor of Applied Clinical Trials, (301) 656-4634 jwechsler@advanstar.com