Research Oversight and Adults with Cognitive Impairment

Biomedical research at times involves adults who are unable to make decisions independently Studies of dementia, psychiatric illnesses, developmental disabilities, and other conditions may involve individuals whose disorders or medications impair their ability to understand the facts necessary to make informed choices about participation. Two types of undesirable errors can occur when researchers recruit participants from groups that include individuals whose decisionmaking abilities are in question. One type of error occurs when investigators enroll incapable adults without the informed and voluntary consent of a responsible surrogate decisionmaker. The other occurs when capable individuals are prevented from making their own choices about study participation. In each case, there is a violation of the Belmont Report's respect-for-persons principle. In the first case, vulnerable persons are inadequately protected from harm, and in the second, individuals able to exercise autonomy are blocked from doing so. (1) These ethical concerns are widely recognized. Indeed, one of the early U.S. research scandals involved the administration of cancer cells to elderly patients with mentally debilitating conditions in the absence of either the subjects' or their surrogates' informed consent. More recently, during the 1990s, investigators conducting a federally funded schizophrenia study failed to provide adequate information about research risks to subjects and their families. These incidents alerted health professionals and the public to problems that can arise when subject populations include adults who may lack decision-making capacity. (2) At the same time, the federal regulations governing human research devote little attention to the distinct concerns that arise when the decisionmaking capacity of adult subjects is in question. According to the Federal Policy for the Protection of Human Subjects, (3) also known as the Common Rule, individuals incapable of issuing valid informed consent may be enrolled in research with the informed consent of a "legally authorized representative." Other Common Rule provisions classify mentally disabled adults as a "vulnerable category of subjects." For the most part, however, the federal regulations give investigators and Institutional Review Boards (IRBs) the responsibility to determine what measures are needed to respect and protect subjects. The rule fails to address several important matters, such as standards for decisionmaking capacity, assent and dissent by incapable adults, and qualifications of an incapable subject's representative. In 1998, the National Bioethics Advisory Commission (NBAC) examined these matters in its Report and Recommendations on Research Involving Persons with Mental Disorders That May Affect Decisionmaking Capacity. (4) The NBAC proposed new federal regulations and made recommendations to others with research oversight duties. State legislators were one target of the NBAC recommendations. To date, the federal government has failed to respond to the NBAC'S proposals for regulatory action. The NBAC recommendations have triggered action at the state level, however. In 2002, legislatures in California and Virginia passed laws specifying which persons could act as research representatives on behalf of adults lacking decisionmaking capacity. (5) Although some states already have laws relevant to surrogate decisionmaking in research, the California and Virginia provisions are more detailed than most. As such, they offer guidance to other states seeking to fill gaps in the federal oversight system. California's new law both identifies and establishes an order of priority for potential research surrogates. Previously designated research agents have the highest priority; followed by legal conservators or guardians, spouses, domestic partners, adult children, custodial parents, adult siblings, and adult grandchildren. In the absence of these family members, the closest relative of those available may fill the research surrogate position. …