Although researchers make every effort to ensure adherence and maintain blinding in placebo-controlled clinical trials, participant perceptions can have unpredictable effects on trial outcomes. For example, a study volunteer’s suspicion of receiving placebo or study drug could influence his or her adherence to the study regimen. As such, it is important to assess factors that could have an influence on trial outcomes when assessing efficacy.
Upon completion of HIV Prevention Trials Network protocol 039, which studied the effect of herpes simplex virus type-2 (HSV-2) suppressive therapy on the risk of HIV-1 acquisition in 3172 HSV-positive/HIV-negative study volunteers, VIDD senior fellow Dr. Shevin Jacob, VIDD statistical research associate Jing Wang, VIDD member Dr. Anna Wald, in collaboration with Dr. Connie Celum and Dr. Jared Baeten from UW Departments of Global Health and Medicine and colleagues gave participants a questionnaire to assess their trial adherence and perceptions. Of particular concern to the researchers was the possibility that the presence of genital ulcer disease symptoms during the study could lead participants to believe they were receiving placebo.
From the 2003 completed questionnaires received, the researchers determined that adherence was generally high, with 72% of participants missing a drug dose fewer than two times per week, and most missed doses were made up by double-doses as directed by the protocol. They found that although there were some significant differences in perceived randomization, the overall differences were small and drug adherence was not compromised by these perceptions. Interestingly, both placebo and drug recipients were much more likely to report that they thought they were receiving acyclovir than placebo, although only approximately a third of participants in either group hazarded a guess. Further, those who suspected they were receiving drug were also more likely to maintain high adherence. Overall, the findings indicate that while study adherence was high, some barriers to adherence remain, such as alcohol use and forgetting study drug while travelling. Post-trial assessments can help identify barriers in specific populations, potentially identifying solutions to these issues for future trial designs.
Jacob ST, Baeten JM, Hughes JP, Peinado J, Wang J, Sanchez J, Reid SE, Delany-Moretlwe S, Cowan F, Fuchs JD, Koblin B, Griffith S, Wald A, Celum C. A Post-Trial Assessment of Factors Influencing Study Drug Adherence in a Randomized Biomedical HIV-1 Prevention Trial. AIDS Behav. 2010 Nov 20.