When it was learned that two patients in the study had become comatose and died shortly after taking the drug, the FDA stepped in and halted the trial. Interestingly, Delaney was later permitted to reinstitute the trial after filing a treatment IND application and forming an institutional review board for oversight. This decision was especially noteworthy in light of the heavy hand of the FDA in past dealings with even minor clinical trial infractions: ''wrongdoing" investigators were often barred for life from conducting further drug trials. It remains to be seen whether the creation of community research consortiums will decrease the interest of advocacy groups in mounting their own trials and increase the level of cooperation and compliance among patients/subjects.

Activists have also become researchers in other less dramatic ways. As noted above, activist representatives now sit on many major scientific committees, including the Executive Committee of the AIDS Clinical Trials Group and several AIDS clinical trial units have community advisory boards. The mission of the latter is currently evolving, but they will likely at least informally review studies to be done at each site. Activists also routinely publish articles on AIDS therapies and have suggested novel approaches to trial design. Indeed, they have been more visible in strategic planning concerning trial design and conduct than the AIDS Clinical Trials Group or other academically based organizations.

The Design of Clinical Trials and Access to Them

AIDS has deepened and broadened critiques of clinical trials as the "gold standard" approach to the testing of new drugs. Such criticism certainly predated AIDS, but it focused largely on the ethics of trials (Beecher, 1966; Rothman, 1987a,b); criticism of AIDS-related trial design also includes methodologic issues.

Traditionally, clinical trials have been designed to ensure that answers are arrived at as quickly as possible and with no associated uncertainties as to whether the drug itself or confounding factors produced the observed effect. Thus, subjects in trials have no serious diseases other than the one under investigation and are not taking other medications. Definitive events are chosen for measurement of drug effect, such as survival, objective clinical improvement (such as disappearance or shrinkage of tumors), or in some cases, the return of an abnormal laboratory or clinical measurement to normal (Weiss and Mazade, 1990). When such laboratory measurements are chosen, they must have been previously shown to correlate to survival or clinical outcomes. For example, since it has been shown that lowering of blood pressure by drugs leads to a decrease in strokes and deaths, new drugs are licensed if they can be shown to lower blood pressure; it is not required that subjects be followed until the occurrence of stroke or death.



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