Longitudinal and repeated cross-sectional cluster-randomization designs using mixed effects regression for binary outcomes: bias and coverage of frequentist and Bayesian methods.
As medical applications for cluster randomization designs become more common, investigators look for guidance on optimal methods for estimating the effect of group-based interventions over time. This study examines two distinct cluster randomization designs: (1) the repeated cross-sectional design in which centres are followed over time but patients change, and (2) the longitudinal design in which individual patients are followed over time within treatment clusters. Simulations of each study design stipulated a multiplicative treatment effect (on the log odds scale), between 5 and 15 clusters in each of two treatment arms, and followed over two time periods. Estimation options included linear mixed effects models using restricted maximum likelihood (REML), generalized estimating equations (GEE), mixed effects logistic regression using both penalized quasi likelihood (PQL) and numerical integration, and Bayesian Monte Carlo analysis. For the repeated cross-sectional designs, most methods performed well in terms of bias and coverage when clusters were numerous (30) and variability across clusters of baseline risk and treatment effect was modest. With few clusters (two groups of five) and higher variability, only the Bayesian methods maintained coverage. In the longitudinal designs, the common methods of REML, GEE, or PQL performed poorly when compared to numerical integration, while Bayesian methods demonstrated less bias and better coverage for estimates of both log odds ratios and risk differences. The performance of common statistical tools for the analysis of cluster randomization designs depends heavily on the precise design, the number of clusters, and the variability of baseline outcomes and treatment effects across centres.
Localio
A Russell
AR
Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6021, USA. rlocalio@cceb.upenn.edu
Berlin
Jesse A
JA
Have
Thomas R Ten
TR
D001499:Bayes Theorem; D015982:Bias; D001699:Biometry; D016000:Cluster Analysis; D003198:Computer Simulation; D003430:Cross-Sectional Studies; D016208:Databases, Factual; D006801:Humans; D016013:Likelihood Functions; D016015:Logistic Models; D008137:Longitudinal Studies; D009010:Monte Carlo Method; D011897:Random Allocation; D016032:Randomized Controlled Trials as Topic / Q000379:methods* / Q000706:statistics & numerical data; D012044:Regression Analysis