Incorporation into a clinical trial can follow several approaches. (1) For a Phase III (efficacy) trial, all active and placebo IVRs can incorporate adherence devices. This will allow determination of adherence and investigation of product efficacy in both perfect adherence and non-adherence scenarios. Additionally, both placebo and active arms of trials can be monitored for adherence to determine patterns of adherence in different groups. Because residual dapivirine in returned IVRs and plasma dapivirine levels were surrogate measures of adherence in ASPIRE, no method for determining IVR use in placebo groups was available. Significant differences in adherence between active and placebo groups may indicate inadequate study blinding, poor randomization of study groups, or other trial design issues. (2) Adherence devices may be incorporated into a subset of Phase 3 study IVRs, both active and placebo. This will allow sub-group adherence data to be extrapolated to the larger study population in studies where it may be logistically difficult to include adherence monitoring for all study participants. Data from temperature-based adherence monitoring can also be combined with plasma drug levels and residual drug in used IVRs to provide temporal IVR use data to increase accuracy of adherence assessment. (3) Devices can be incorporated into IVRs in Phase 1 and Phase 2 trials as a “perfect” measure of adherence that can be used to evaluate non-objective adherence measures and to develop additional adherence endpoints, such as compounds adsorbed into the IVR from vaginal fluids, drug levels in blood or other relevant compartments, and residual drug in used IVRs.