Efficacy dilution in randomized placebo-controlled vaginal microbicide trials
Open Access
- 9 October 2009
- journal article
- Published by Springer Science and Business Media LLC in Emerging Themes in Epidemiology
- Vol. 6 (1), 5
- https://doi.org/10.1186/1742-7622-6-5
Abstract
To date different vaginal gel microbicides have been evaluated in phase 2b/3 trials, but none have demonstrated effectiveness for preventing HIV infection. Failure to demonstrate effectiveness however does not necessarily indicate that a product is truly inefficacious, as several sources of efficacy dilution may compromise our ability to identify products that may have been truly efficacious. For four individual sources of dilution, we describe the dilution mechanisms and quantify the expected effectiveness. An overall expected effectiveness that combines all sources of dilution in a trial is derived as well. Under conditions that have been observed in recent microbicide trials, the overall expected effectiveness assuming an active gel with true efficacy of 50% and 75% are in the range of [16%; 33%] and [28%; 50%], respectively, when considering the four major sources of dilution. In contrast the diluting effect due to adherence alone (assuming an adherence of 80%) leads to higher expected effectiveness, 40% and 60% assuming an active gel with true efficacy of 50% and 75%, respectively. Individual sources of dilution may demonstrate a small effect when evaluated independently, but the overall dilution effect in a trial with several sources of dilution can be quite substantial. Currently planned phase 2b/3 microbicide trials of new candidate vaginal microbicides are not immune from these shortcomings. A good understanding of dilution effects is necessary to properly interpret microbicide trial results and to identify products worthy of further development and evaluation. Greater attention should be devoted to reducing and assessing the impact of efficacy dilution and to carefully selecting the effect size in the design of future trials.Keywords
This publication has 19 references indexed in Scilit:
- Vaginal microbicides and the prevention of HIV transmissionThe Lancet Infectious Diseases, 2008
- Effectiveness of Cellulose Sulfate Vaginal Gel for the Prevention of HIV Infection: Results of a Phase III Trial in NigeriaPLOS ONE, 2008
- Lack of Effectiveness of Cellulose Sulfate Gel for the Prevention of Vaginal HIV TransmissionNew England Journal of Medicine, 2008
- Persisting with prevention: The importance of adherence for HIV preventionEmerging Themes in Epidemiology, 2008
- SAVVY Vaginal Gel (C31G) for Prevention of HIV Infection: A Randomized Controlled Trial in NigeriaPLOS ONE, 2008
- SAVVY® (C31G) Gel for Prevention of HIV infection in Women: A Phase 3, Double-Blind, Randomized, Placebo-Controlled Trial in GhanaPLOS ONE, 2007
- Pregnancy in Effectiveness Trials of HIV Prevention AgentsSexually Transmitted Diseases, 2007
- Determining the feasibility of utilizing the microbicide applicator compliance assay for use in clinical trialsContraception, 2007
- Will microbicide trials yield unbiased estimates of microbicide efficacy?Contraception, 2005
- A Controlled Trial of Nonoxynol 9 Film to Reduce Male-to-Female Transmission of Sexually Transmitted DiseasesNew England Journal of Medicine, 1998