Likelihood Methods for Treatment Noncompliance and Subsequent Nonresponse in Randomized Trials

Abstract

While several new methods that account for noncompliance or missing data in randomized trials have been proposed, the dual effects of noncompliance and nonresponse are rarely dealt with simultaneously. We construct a maximum likelihood estimator (MLE) of the causal effect of treatment assignment for a two-armed randomized trial assuming all-or-none treatment noncompliance and allowing for subsequent nonresponse. The EM algorithm is used for parameter estimation. Our likelihood procedure relies on a latent compliance state covariate that describes the behavior of a subject under all possible treatment assignments and characterizes the missing data mechanism as in Frangakis and Rubin (1999, Biometrika 86, 365-379). Using simulated data, we show that the MLE for normal outcomes compares favorably to the method-of-moments (MOM) and the standard intention-to-treat (ITT) estimators under (1) both normal and non-normal data, and (2) departures from the latent ignorability and compound exclusion restriction assumptions. We illustrate methods using data from a trial to compare the efficacy of two antipsychotics for adults with refractory schizophrenia.