Augmented trial designs for evaluation of principal surrogates.

ABSTRACT: Observation of counterfactual intermediate responses, and evaluation of them as candidate surrogates, is complicated in a standard randomized trial as half of the responses are systematically missing by design. Although some augmentation procedures exist for obtaining counterfactual responses, they are specific to vaccine trials. We outline extensions to the existing augmentations and suggest augmentations of three trial designs outside the setting of vaccines. We outline the assumptions needed to identify the causal estimands of interest under each augmented design, under which standard likelihood-based methods can be used to evaluate intermediate responses as principal surrogates. Two of these designs, crossover and individual stepped-wedge, allow for the observation of clinical endpoint

SUBMITTER: Gabriel EE 

PROVIDER: S-EPMC4915608 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature