Aim
Trial run-in phases are sometimes used to select adherent patients, but the methods employed lack clear regulatory guidance and there are concerns about the transparency of reporting. This review aims to characterise the methods utilized for adherence measurement and reporting in run-in studies.

Methods
Clinicaltrials.gov using was searched using the terms "run*in" OR "lead*in" OR "enrichment” OR “single-blind placebo.” Studies were included if they were phase 2 or 3 interventional studies with published results, containing the protocol and statistical analysis plan. The study start date (first patient enrolled) was restricted to 01/01/2010 to 04/03/2024. The Risk of Bias tool for Observational Adherence Studies (RoBOAS) and the ESPACOMP medication adherence reporting guidelines (EMERGE) were used to assess methodological and reporting quality.

Results
249 studies were identified, 34 were included for the analysis, of which 8 specified adherence to be the main purpose of the run-in. Run-ins were generally of poor methodological and reporting quality, with most using pill counts to measure adherence over 2 weeks, and only 23/34 having complete reporting of the adherence measurement, metric, and method of data aggregation. No studies reported the adherence phase studied.

Discussion and conclusion
Our review suggests that medication adherence is poorly reported in the run-in phase of drug trials, with the methods prone to bias. The findings support the need to develop guidelines on the reporting of medication adherence during the run-in phase, and should serve to inform future trial design, conduct and reporting, as well as have regulatory implications.