Guideline for the Measurement, Analysis and Reporting of Medication Adherence during the Run-in phase of clinical trials (MARMAR)

BACKGROUND: Trial run-in phases are sometimes used to select participants into clinical trials who are most likely to remain adherent to study medications. The study designs and data analysis methods employed lack clear regulatory guidance while reporting is not consistent or transparent. This study aims to develop a consensus guideline for the Measurement, Analysis, and Reporting of Medication Adherence during the Run-in phase (MARMAR) of clinical trials. METHODS: Initial "items" (specific statements relating to the measurement, analysis, and reporting of medication adherence during trial run-in phases) were generated following a systematic review of trial run-in phases. Items were split into 2 domains (methods and reporting), refined through a pilot exercise and subsequently evaluated using a two-round modified Delphi survey of international experts in medication adherence and clinical trials. Participants were recruited via e-mailing lists. In survey round one, respondents rated the importance of items across a scale labelled strongly agree to strongly disagree and provided free-text comments. In survey round two, respondents categorised items as essential or desirable and suggested alternative wording. A final consensus meeting of the research team was held to finalise the guideline. Guideline development was endorsed by the International Society for Medication Adherence (ESPACOMP) and registered with EQUATOR. RESULTS: In round one, 49 respondents rated 29 items, with 64-100% (mean 86.5%) of experts scoring an item 4 or 5. Consensus was reached for 28 items, and 226 free-text comments led to merging overlapping items. In round two, 27 respondents rated 20 revised items, with 33-100% (mean 78.7%) of experts judging them essential and providing 66 free-text comments. The final MARMAR guideline comprises 20 items: 9 methodological and 11 reporting considerations for medication adherence during trial run-in phases. CONCLUSION: The MARMAR guideline provides the first structured, consensus-based guideline specifically focused on medication adherence during trial run-in phases. By supporting more transparent and rigorous measurement, analysis and reporting, it should serve to improve the quality of future trial run-in phases.