The choice of a primary endpoint is an important issue when designing a clinical trial. It is common to use composite endpoints as a primary endpoint because it increases the number of observed events, captures more information and is expected to increase the power. However, combining events that have no similar clinical importance and have different treatment effects makes the interpretation of the results cumbersome and might reduce the power of the corresponding tests. Gómez and Lagakos proposed the ARE (asymptotic relative efficiency) method to choose between a composite or one of its components as primary endpoint comparing the efficacy of a treatment based on the times to each of these endpoints. The aim of this paper is to expand the ARE method to binary endpoints. We show that the ARE method depends on six parameters including the degree of association between components, event proportion, and effect of therapy given by the corresponding odds ratio of the single endpoints. A case study is presented to illustrate the methodology. We conclude with efficient guidelines for discerning which could be the best suited primary endpoint given anticipated parameters.
This is the peer reviewed version of the following article: Bofill, M., Gomez, G. Selection of composite binary endpoints in clinical trials. "Biometrical journal", 12 Octubre 2017, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/bimj.201600229/pdf. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Interval-censored covariates are sometimes encountered in longitudinal studies and considered as possible predictors in a regression model. This paper, motivated by an AIDS study, proposes an implementation in R for the estimation of parameters and the assessment of the assumptions of a linear regression model with an interval-censored covariate. The properties of the parameters estimators and the behavior of three proposed residuals are addressed through two simulation studies. Also, guidelines are provided to check the goodness-of-fit of the fitted model in terms of the length of the censoring interval of the covariate. The methodology is illustrated with real data coming from the AIDS study. R functions and scripts are provided.