Researchers Call for Improvements in Trial Design to Test Biomedical Interventions to Prevent HIV

It is "imperative to prioritize the identification and implementation of more effective behavioral and nonvaccine biomedical interventions" to prevent HIV, as well as to "design, fund and conduct these trials in ways that give them the best chance of success," Stephen Lagakos, professor of biostatistics at the Harvard School of Public Health, and Alicia Gable, a senior program officer at the Institute of Medicine, write in a New England Journal of Medicine perspective piece. The authors note that many late-stage biomedical trials -- including those studying the use of vaginal microbicide gels, diaphragms, pre-exposure prophylaxis and two types of HIV vaccines -- failed to demonstrate a benefit in preventing HIV. In addition, while research has shown that several behavioral interventions have reduced the rates of sexually transmitted infections, none showed a reduction in HIV infection, Lagakos and Gable write.

According to Lagakos and Gable, the failure of recent late-stage biomedical HIV-prevention trials reveals the "[s]hortcomings" in research design. They write, "Design deficiencies led to premature termination of some trials because of inadequate research before the trial began, poor site preparation or lack of community engagement." The authors note that "key" problems with trial design include estimating the expected HIV incidence in the trial population, assessing participants' adherence and risk-behavior, and the lack of reliable end points.

They call on researchers and trial sponsors to "intensify" investment in the development of "safe, easy-to-use biomedical interventions," as well as improve "preclinical and early-stage clinical testing, and prioritization of products for later-stage testing." In addition, they recommend that future trials be adequately planned and include "reliable estimations of the rates of HIV infection, pregnancy, loss to follow-up and nonadherence to determine an adequate sample size and trial duration" (Lagakos/Gable, NEJM, 4/10).

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