Some design issues in trials of microbicides for the prevention of HIV infection.
Trials for the prevention of human immunodeficiency virus (HIV) infection that evaluate microbicides provide significant design challenges. Three of these design issues deserve more careful consideration. The first issue relates to the benefits of using both blinded and unblinded control groups when the placebo regimen may not be inert and when the effectiveness of an intervention heavily depends on behavioral, as well as biological, factors. The second issue relates to the strength of evidence required for regulatory approval for the marketing of drugs and biologics when only a single pivotal phase 3 clinical trial has provided such evidence. The third issue relates to the appropriate next step after the completion of phase 1 trials, as well as the specific merits of conducting phase 2b screening trials that assess the effects on the same clinical efficacy end point that will be the primary end point in a phase 3 trial. The issues considered in microbicide trials for the prevention of HIV infection are also of importance in many other clinical scenarios.
Fleming
Thomas R
TR
Department of Biostatistics, University of Washington, Seattle, Washington 98195, USA. tfleming@u.washington.edu
Richardson
Barbra A
BA
D019380:Anti-HIV Agents / Q000627:therapeutic use; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic / Q000379:methods* / Q000592:standards / Q000706:statistics & numerical data; D017326:Clinical Trials, Phase III as Topic / Q000592:standards / Q000706:statistics & numerical data; D035061:Control Groups; D017277:Drug Approval; D005260:Female; D015658:HIV Infections / Q000517:prevention & control*; D006801:Humans; D007223:Infant; D007743:Labor, Obstetric; D019829:Nevirapine / Q000627:therapeutic use; D017410:Practice Guidelines as Topic; D011247:Pregnancy; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D012306:Risk
D019380:Anti-HIV Agents; D000890:Anti-Infective Agents; D019829:Nevirapine