title: Closed-form REML estimators and sample size determination for mixed effects models for repeated measures under monotone missingness.
abstract: We derive the closed-form restricted maximum likelihood estimator and Kenward-Roger's variance estimator for fixed effects in the mixed effects model for repeated measures (MMRM) when the missing data pattern is monotone. As an important application of the analytic result, we present the formula for calculating the power of treatment comparison using the Wald t-test with the Kenward-Roger adjusted variance estimate in MMRM. It allows adjustment for baseline covariates without the need to specify the covariate distribution in randomized trials. A simple two-step procedure is proposed to determine the sample size needed to achieve the targeted power. The proposed method performs well for both normal and moderately non-normal data even in small samples (n=20) in simulations. An antidepressant trial is analyzed for illustrative purposes. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Shire, 300 Shire Way, Lexington, 02421, MA, U.S.A.
authors.forename: Yongqiang
authors.identifier: 0000-0003-4444-1791
authors.initials: Y
authors.lastname: Tang
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy; D006801:Humans; D016013:Likelihood Functions; D015233:Models, Statistical; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D018401:Sample Size; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents
keywords: Kenward-Roger's variance estimator; power and sample size; restricted maximum likelihood