Modeling variability in treatment effects for cluster randomized controlled trials using by-variable smooth functions in a generalized additive mixed model.

ABSTRACT

Variability in treatment effects is common in intervention studies using cluster randomized controlled trial (C-RCT) designs. Such variability is often examined in multilevel modeling (MLM) to understand how treatment effects (TRT) differ based on the level of a covariate (COV), called TRT × COV. In detecting TRT × COV effects using MLM, relationships between covariates and outcomes are assumed to vary across clusters linearly. However, this linearity assumption may not hold in all applications and an incorrect assumption may lead to biased statistical inference about TRT × COV effects. In this study, we present generalized additive mixed model (GAMM) specifications in which cluster-specific functional relationships between covariates and outcomes can be modeled using by-variable smooth functions. In addition, the implementation for GAMM specifications is explained using the mgcv R package (Wood, 2021). The usefulness of the GAMM specifications is illustrated using intervention data from a C-RCT. Results of simulation studies showed that parameters and by-variable smooth functions were recovered well in various multilevel designs and the misspecification of the relationship between covariates and outcomes led to biased estimates of TRT × COV effects. Furthermore, this study evaluated the extent to which the GAMM can be treated as an alternative model to MLM in the presence of a linear relationship.