Title: A method for improving the efficiency of phase II trials
Authors: Chien-Ju Lin - MRC Biostatistics Unit University of Cambridge (United Kingdom) [presenting]
James Wason - Institute of Health and Society - Newcastle University (United Kingdom)
Abstract: In many trials, duration between patient enrollment and an event occurring is used as the efficacy endpoint. Common endpoints of this type include the time until relapse, progression to the next stage of a disease, or time until remission. The criteria of an event may be defined by multiple components, some of which are a continuous measurement being above or below a threshold. Typical analyses consider all components as binary variables and label patients as having events or non-events at multiple time points. This is analysed through constructing and testing survival functions using Kaplan-Meier, parametric models or Cox models. This approach ignores information on the continuous form of measurements in defining events. We propose a method to make use of this information to improve the precision of analyses using these types of endpoints. We use joint modelling of the continuous and binary components to construct survival curves. We show how to compute confidence intervals for quantities of interest. We assess the properties of the proposed method using simulations and data from a phase II cancer trial and an observational study of in renal disease. Finally, we showcase a R-Shiny app that implements the proposed method.