Medication adherence in clinical trials: measurement methods, methodological challenges, and reporting standards

INTRODUCTION: Medication adherence is a critical determinant of therapeutic exposure, efficacy estimation, and safety evaluation in clinical trials. Despite its fundamental role, adherence remains inconsistently defined, measured, and reported across the clinical trial landscape. AREAS COVERED: This review evaluates contemporary conceptual frameworks and measurement strategies for medication adherence in clinical trials. It examines the implications of suboptimal adherence for trial design, statistical analysis, and the interpretation of therapeutic outcomes, while addressing the impact on both internal and external validity. EXPERT OPINION: There is a necessary transition from conventional, binary models of 'compliance' to the multidimensional ABC taxonomy (initiation, implementation, discontinuation and persistence), which characterizes adherence as a dynamic, longitudinal process. Traditional assessment methods - such as self-reports, pill counts, and pharmacy refill metrics - vary in feasibility but are often limited by recall bias and poor temporal resolution. Conversely, electronic monitoring and digitally enabled technologies provide more objective, high-resolution proxy measures that are essential for better characterizing real-world medication-taking behavior. However, persistent methodological heterogeneity and a lack of standardized reporting undermine the comparability of trial results. The adoption of harmonized reporting standards, specifically the EMERGE guidelines, and the prospective integration of digital adherence assessment is vital to strengthening the evidentiary integrity of future therapeutic evidence.