On the analysis of composite measures of quality in medical research.

Abstract

Composite endpoints are commonplace in biomedical research. The complex nature of many health conditions and medical interventions demand that composite endpoints be employed. Different approaches exist for the analysis of composite endpoints. A Monte Carlo simulation study was employed to assess the statistical properties of various regression methods for analyzing binary composite endpoints. We also applied these methods to data from the BETTER trial which employed a binary composite endpoint. We demonstrated that type 1 error rates are poor for the Negative Binomial regression model and the logistic generalized linear mixed model (GLMM). Bias was minimal and power was highest in the binomial logistic regression model, the linear regression model, the Poisson (corrected for over-dispersion) regression model and the common effect logistic generalized estimating equation (GEE) model. Convergence was poor in the distinct effect GEE models, the logistic GLMM and some of the zero-one inflated beta regression models. Considering the BETTER trial data, the distinct effect GEE model struggled with convergence and the collapsed composite method estimated an effect, which was greatly attenuated compared to other models. All remaining models suggested an intervention effect of similar magnitude. In our simulation study, the binomial logistic regression model (corrected for possible over/under-dispersion), the linear regression model, the Poisson regression model (corrected for over-dispersion) and the common effect logistic GEE model appeared to be unbiased, with good type 1 error rates, power and convergence properties.