Statistical analysis
There is no control group for comparison in this study. The main goal was not to compare between the three different placebo modalities, but to obtain overall rates of acceptability, adherence, and safety of each modality. The selected sample size provides at least 90% power to rule out rates of acceptability or adherence below 70%.Baseline characteristics are described for all enrolled participants. The study’s safety endpoint was evaluated among participants who received at least one of the study products (excluding any study periods when participants did not receive a product). The acceptability and adherence primary endpoints were evaluated among participants who received all three study products and completed the scheduled product use (which we refer to as the “per-protocol” subset), thus providing relevant data from all three periods of study. To support the generalizability of acceptability and adherence results, we compared baseline characteristics between participants in the per-protocol subset and those who were lost to follow-up.For the safety endpoint, the proportion of participants with Grade 2 or higher related AEs is reported, along with a 95% confidence interval (CI) (Clopper-Pearson method). For adherence and acceptability endpoints, the proportion of participants classified as adherent, or who reported a high acceptability score, are also provided, along with 95% CIs.To test for potential effects of the assigned sequence and/or sites in the overall acceptability and adherence, generalized linear mixed models with a logistic link function were used. The participant’s assigned sequence, site, and the modality used in the study period were included as fixed effects, with a random effect at the participant level to account for the cross-over design. To test if overall differences exist between sites or assigned sequences, omnibus likelihood ratio tests were used. No adjustment of p-values was performed.