Issues in the design of drug trials for AIDS

Although the fundamental principles that drive the design, conduct, and analysis of clinical trials are as applicable to AIDS as to other diseases, there is no question that we have been confronted with unusually difficult challenges in studying therapeutic approaches in this disease area. Treatments are being developed that show great promise, but when investigated further some may be seen to offer no clinical benefit and others may do active harm through toxicity. A group of biostatisticians, meeting in association with the AIDS Clinical Trials Group (ACTG), has discussed and written a report on a number of issues, primarily related to principles of study design, with the goal of stimulating thought on new study designs and the timely implementation of well-designed trials to identify effective treatment strategies for HIV-infected populations. These issues include (1) progression of clinical trials through phases, (2) choices of outcomes, (3) breadth and complexity of clinical trials (eligibility criteria and "low-tech" trials, (4) alternative designs to be used in randomized trials, and (5) the concept of randomized clinical trials as a desirable option, both for patients and for science. The current HIV epidemic makes the requirements of obtaining valid scientific comparisons more important, not less so, but the challenge is to expedite this process.