Presentation: Design challenges for RCTs assessing new HIV prevention drugs in the era of Pre-exposure Prophylaxis: What do you do when adherence changes everything?
Speaker: Deborah Donnell, Ph.D., Associate Member, Vaccine and Infectious Disease Division, Public Health Sciences Division, Fred Hutchinson Cancer Research Center
Abstract: Antiretroviral drugs for prevention of HIV, both as treatment for prevention and as pre-exposure prophylaxis (PrEP), are highly effective when taken consistently and correctly. However, adherence to daily oral PrEP remains a challenge and long-acting formulations of antiretroviral drugs, vaccines and monoclonal antibodies may have significant advantages for prevention. Designing studies to provide compelling evidence that new products are effective for preventing HIV acquisition when there are existing proven effective methods is a new challenge in HIV prevention.
Two randomized clinical trials are proceeding to test the efficacy of a new injectable drug compared to the active comparator FTC/TDF PrEP. The design of these trials is highly dependent on the unknown adherence to the active comparator. Adherence affects the hypothesis, the sample size and the effect size of the trial. We will present the strategy used to design these trials, and approaches we have developed for assessing an adapted hypothesis at the trial conclusion, based on pre-specified adherence assessment from the trial itself and meta-analysis of evidence of efficacy from prior trials.