Pharmacy Refill Synchronization and Antiretroviral Therapy Continuity in South African Public Health Systems: A Target-Trial Emulation of Medication Possession Ratio

Pharmacy refill synchronization has been proposed as a structural intervention to reduce antiretroviral therapy interruptions in South African public health systems, but the observational evidence base for its effect on medication possession ratio is confounded by indication and by differential retention in care. Because no empirical dataset is analysed here, the paper characterises the operating characteristics of the proposed design under a declared variance structure: between-cluster standard deviation 6.0, residual standard deviation 4.5 and intraclass correlation 0.64. Power was estimated across 2000 replications per design cell for cluster counts of 8, 16, 24 and 32 and effect sizes of 3, 5 and 8 percentage points. Under these parameters, 54 clusters are required to detect a 5 percentage point difference at 80 per cent power. The framework clarifies which causal question refill synchronization research can answer, identifies the confounding structures that a target-trial emulation must address, and specifies the design parameters under which a cluster-level evaluation would be adequately powered.