Noncompliance in AIDS Research
Arras, John D., The Hastings Center Report
Noncompliance in AIDS Research
From Nuremberg to the mid-1980s, the ethics of research has concentrated exclusively on the rights of patient-subjects. Noncompliance with protocols--either lying to get in a study or, once in, failing to adhere to its requirements--has always been a nuisance, but never a major problem requiring public discussion. In the past, noncompliance could largely be chalked up to the frailty inherent in human nature. Subjects usually broke the rules because of carelessness, despair of getting better, or adverse reactions.
The advent of AIDS and AIDS research has transformed a pervasive but minor problem into a major ethical-political issue. Although reliable statistics on noncompliance are unavailable, for obvious reasons, anecdotal reports of rampant "lying and cheating" are numerous.  Participants lie to get into studies (often with the help of their own physicians)  and, once enrolled, lie about their medical condition and level of compliance. They attempt to frustrate the use of placebos by dropping out of studies if randomized to the placebo arm; by analyzing the drugs they receive, thereby unblinding the study; and by pooling drugs, which ensures that they will receive some portion of the active substance while playing havoc with assigned dosage levels. This latter problem is often exacerbated by subjects who, fearful of receiving excessively high amounts of experimental drugs, substitute their own notions of appropriate dosages for the terms of the protocol. Finally, participants frequently take other nonvalidated therapies in addition to the drugs under study, thereby possibly masking the beneficial or harmful effects of those drugs.  Clearly, the magnitude of noncompliance in AIDS research threatens the validity of many important ongoing clinical trials.
Why has noncompliance become such a serious problem in the age of AIDS? Three complementary explanations come to mind. First, the desperate quest for access to health care has largely eclipsed altruism as a motive for participating in clinical trials. In spite of the fact that the drugs under study are experimental, persons with AIDS (PWAs) and HIV-infected persons have come to view them either as the exclusive source of therapeutic benefit or else (as in studies using placebos) as their only chance of such benefit. Some potential subjects are primarily interested in access to experimental drugs, many of which have been unavailable off protocol. Others may be able to purchase a drug through the market or so-called "guerrilla clinics," but desire entry into trials to acquire the needed drug free of charge. Still others, mostly the poor and uninsured, may be relatively disinterested in obtaining experimental drugs, but keenly desirous of obtaining the modicum of primary care that often comes with participation in hospital-based clinical trials. For all such patient-subjects, advancing their own self-interest--rather than the future of medical science or the plight of future sufferers of AIDS--seems to be the driving motivational force.
Secondly, many infected persons and PWAs are desperate to obtain help. Rightly cognizant of AIDS as a lethal threat to their very existence and of the impotence of current medical science, many infected persons will "do anything," including lying and cheating, to obtain what they think they need to live. Access to clinical trials is the "only hope" for such patients, for whom noncompliance is not so much an ethical problem as a means of personal survival.
Thirdly, many potential subjects are profoundly alienated from "mainstream" society. Unlike most cancer patients, who are often equally desperate for "last chance" cures, the ranks of AIDS patients are largely filled with persons who, prior to their illness, had been entirely marginalized. While some gay men and drug users might still identify very strongly with the majority culture, many no doubt are openly hostile to the larger society that has criminalized and stigmatized their way of life. …