Adaptive pair-matching in randomized trials with unbiased and efficient effect estimation

• Published in: Statistics in medicine Vol. 34; no. 6; pp. 999 - 1011
• Main Authors: Balzer, Laura B., Petersen, Maya L., van der Laan, Mark J.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 15.03.2015; Wiley Subscription Services, Inc
• Subjects: adaptive designs; Africa; Anti-Retroviral Agents - therapeutic use; Antiretroviral drugs; causal inference; Clinical trials; Cluster Analysis; Computer Simulation; Data Interpretation, Statistical; Drug therapy; efficiency; Estimating techniques; HIV; HIV Infections - drug therapy; Human immunodeficiency virus; Humans; Linear Models; Logistic Models; Loss control; Medical treatment; pair-matching; Randomized Controlled Trials as Topic - methods; randomized trials; Research Design; targeted minimum loss based estimation (TMLE); Africa; East Africa; randomized trials; efficiency; adaptive designs; targeted minimum loss based estimation (TMLE); causal inference; pair-matching
• ISSN: 0277-6715; 1097-0258; 1097-0258
• DOI: 10.1002/sim.6380

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 a consequence, the observed data cannot be considered as n/2 independent, identically distributed pairs of units, as common 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, conditional the baseline covariates of the n study units. By avoiding estimation of the covariate distribution, estimators of this conditional effect will often be more precise than estimators of the marginal effect. We contrast the unadjusted estimator with targeted minimum loss based estimation 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 study, an ongoing community randomized trial to evaluate the impact of immediate and streamlined antiretroviral therapy on HIV incidence in rural East Africa. Copyright © 2014 John Wiley & Sons, Ltd.