Given the recent failure of a number of randomized trials to demonstrate effectiveness of proposed methods for prevention of sexual transmission of HIV, novel approaches to study design and analysis that address adherence and other post-randomization behaviors are of increasing interest. The inclusion of a mandatory condom use intervention in all randomized groups in such trials can significantly impact interpretation of study results, especially when levels of use observed in the study may differ from real world levels.We use quantitative examples and simulations to investigate this issue, focusing on effectiveness estimated by the standard intention to treat analysis approach. We also assess the application of recently developed methods for estimating the causal effect of treatment assignment, accounting for observed levels of condom use.Results show that observed levels of condom use may have substantial impacts on the conclusions drawn from standard analyses of prevention trials, with the most serious effects observed in studies with unblinded control groups. Causal estimation methods accounting for post-randomization behaviors can help clarify these impacts by focusing attention on effectiveness for controlled levels of condom use.Supplemental causal analyses that account for post-randomization condom use may provide useful information about possible efficacy that complement standard analyses. However, interpretation of results may be limited by the quality of available data on adherence behavior, and limited statistical power.
©2011 Walter de Gruyter GmbH & Co. KG, Berlin/Boston