Adaptive Pair-Matching in the SEARCH Trial and Estimation of the Intervention Effect

In randomized trials, pair-matching is an intuitive design strategy to protect study validity and to potentially increase study power. In a common design, candidate units are identified, and their baseline characteristics used to create the best n/2 matched pairs. Within the resulting pairs, the intervention is randomized, and the outcomes measured at the end of follow-up. We consider this design to be adaptive, because the construction of the matched pairs depends on the baseline covariates of all candidate units. As consequence, the observed data cannot be considered as n/2 independent, identically distributed (i.i.d.) pairs of units, as current practice assumes. Instead, the observed data consist of n dependent units. This paper explores the consequences of adaptive pair-matching in randomized trials for estimation of the average treatment effect, given the baseline covariates of the n study units. We contrast the unadjusted estimator with targeted minimum loss-based estimation (TMLE) and show substantial efficiency gains from matching and further gains with adjustment. This work is motivated by the Sustainable East Africa Research in Community Health (SEARCH) study, a community randomized trial to evaluate the impact of immediate and streamlined antiretroviral therapy on HIV incidence in rural East Africa.

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