Sequential analysis methodology for a Poisson GLMM with applications to multicenter randomized clinical trials

Abstract

Sequential analyses in clinical trials have ethical and economic advantages over fixed sample size methods. The sequential probability ratio test (SPRT) is a hypothesis testing procedure which evaluates data as it is collected. The original SPRT was developed by Wald for one-parameter families of distributions and later extended by Bartlett to handle the case of nuisance parameters. However, Bartlett's SPRT requires independent and identically distributed observations. In this paper we show that Bartlett's SPRT can be applied to generalized linear model (GLM) contexts. Then we propose an SPRT analysis methodology for a Poisson generalized linear mixed model (GLMM) that is suitable for our application to the design of a multicenter randomized clinical trial that compares two preventive treatments for surgical site infections. We validate the methodology with a simulation study that includes a comparison to Neyman–Pearson and Bayesian fixed sample size test designs and the Wald SPRT.