Variability in Causal Effects and Noncompliance in a Multisite Trial: A Bivariate Hierarchical Generalized Random Coefficients Model for a Binary Outcome

Within each of 170 physicians, patients were randomized to access e-assist, an online program that aimed to increase colorectal cancer screening (CRCS), or control. Compliance was partial: 78.34% of the experimental patients accessed e-assist while no controls were provided the access. Of interest are the average causal effect of assignment to treatment and the complier average causal effect as well as the variation of these causal effects across physicians. Each physician generates probabilities of screening for experimental compliers (experimental patients who accessed e-assist), control compliers (controls who would have accessed e-assist had they been assigned to e-assist), and never takers (patients who would have avoided e-assist no matter what). Estimating physician-specific probabilities jointly over physicians poses novel challenges. We address these challenges by maximum likelihood, factoring a "complete-data likelihood" uniquely into the conditional distribution of screening and partially observed compliance given random effects and the distribution of random effects. We marginalize this likelihood using adaptive Gauss-Hermite quadrature. The approach is doubly iterative in that the conditional distribution defies analytic evaluation. Because the small sample size per physician constrains estimabiliity of multiple random effects, we reduce their dimensionality using a shared random effects model having a factor analytic structure. We assess estimators and recommend sample sizes to produce reasonably accurate and precise estimates by simulation, and analyze data from a trial of a CRCS intervention. [This is the online first version of an article published in "Statistics in Medicine."]