Ethical Values and Legal Regulation

UNTIL THE EARLY 1970S, R. J. REYNOLDS, DOW Chemical, the US Army, major pharmaceutical companies, and other sponsors conducted a wide variety of research on prisoners—a captive, vulnerable, and easily accessible population. During that time, approximately 90% of all pharmaceutical research was conducted on prisoners, who also were subjected to biochemical research ranging from testing diet drinks and simple detergents to studies involving dioxin and chemical warfare agents. From 1962 to 1966, for example, 33 pharmaceutical companies tested 153 experimental drugs at Holmesburg Prison in Philadelphia, including a Retin-A (tretinoin) study in which researchers did not seek informed consent and prisoners were not adequately treated for pain. By the mid-1970s, biomedical research in prisons sharply declined as knowledge of the exploitation of prisoners began to emerge and the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research was formed. Federal regulations to protect human subjects of research were established in 1974 and modified and codified in 1981. The regulations were revised in 1991 as the Federal Policy for the Protection of Human Subjects and became known as the Common Rule. The Common Rule applies to research funded by the Department of Health and Human Services (DHHS); to private institutions that undertake a Federal-Wide Assurance of Compliance; and, with broad exceptions, to 16 additional federal agencies. The US Food and Drug Administration has similar regulations for research involving the products it regulates. The Common Rule contains requirements for institutional review board (IRB) review, informed consent, and risk/benefit analysis. These regulations also provide extra protections for particularly vulnerable populations: pregnant women, fetuses, and neonates (subpart B); prisoners (subpart C); and children (subpart D). Subpart C, promulgated in 1978 in response to recommendations from the national commission, strictly limits research involving prisoners. However, federal agencies (except for the DHHS, Central Intelligence Agency, and Social Security Administration) have not adopted subpart C, perhaps because it is so restrictive. In 1981, Food and Drug Administration regulations specifically applicable to prisoners were blocked by a lawsuit brought by prisoners wishing to participate in research. In 1997, the Bureau of Prisons adopted its own additional regulations for research involving prisoners in federal custody. Under subpart C, research on prisoners must present no more than minimal risk, defined as the risk of harm normally encountered in their daily lives or in the routine medical, dental, or psychological examination of healthy persons. Subpart C identifies 4 categories of permitted research relating to (1) possible causes, effects, and processes of incarceration; (2) prisons as institutional structures or prisoners as incarcerated persons; (3) conditions particularly affecting prisoners as a class; and (4) practices that have the intent and reasonable probability of improving the health or well-being of research participants. Categories 3 and 4 may proceed only after the Secretary of Health and Human Services has consulted with experts and published a Federal Register notice of the intent to approve. A fifth category of research was permitted when subpart C was amended in 2003 to allow epidemiologic research on specified diseases in which prisoners are included in the population of interest but are not the sole study group. In such a case, the IRB must determine that the epidemiologic research involves minimal risk or no more than inconvenience to prisoner-subjects. The definition of minimal risks is so narrow and confusing (eg, are the risks to be measured in terms of threats encountered in life on the outside, or within prison?), and the secretarial review is so onerous (taking months or years to review), that research subject to subpart C is often avoided. Because these regulations apply only to a few federal agencies and institutions that voluntarily comply with them through a Federal-Wide Assurance of Compliance, the majority of prison research is conducted outside the purview of subpart C. Federal oversight of research in prisons, therefore, is either too restrictive (effectively impeding responsible research) or inapplicable (opening the door to exploitation or abuse). It is in this context that the DHHS asked the Institute of Medicine (IOM) to consider the need for de-