Survival analysis for AdVerse events with VarYing follow-up times (SAVVY) -- comparison of adverse event risks in randomized controlled trials

Abstract

Background: Analyses of adverse events (AEs) are an important aspect of benefitrisk and health-technology assessments of therapies. The SAVVY (Survival analysis for AdVerse events with Varying follow-up times) project aims to improve the analyses of AE data in clinical trials through the use of survival techniques appropriately dealing with varying follow-up times and competing events (CEs). In an empirical study including randomized clinical trials (RCT) from several sponsor organisations the effect of varying follow-up times and competing events on comparisons of two treatment arms with respect to AE risks is investigated. Methods: CEs definition does not only include death before AE but also end of follow-up for AEs due to events possibly related to the disease course or safety of the treatment. The comparisons of relative risks (RRs) of standard probability-based estimators to the gold-standard Aalen-Johansen estimator or hazard-based estimators to an estimated hazard ratio (HR) from Cox regression are done descriptively, with