Hierarchical Composite Endpoints in COVID-19: The DARE-19 Trial
Samvel B. Gasparyan, Elaine K. Kowalewski, Joan Buenconsejo, Gary G. Koch · 2023
Prioritized outcome composite endpoints are a general class of endpoints combining different clinical outcomes of patients into a composite so as to preserve their different natures. A particular case of these endpoints is the hierarchical composite endpoint (HCE). It is evaluated in a fixed follow-up period and accounts for the patient’s clinically most important outcome for the analysis. HCEs are analyzed using win odds and other win statistics. We provide the example of the DARE-19 clinical trial which constructed an HCE in the COVID-19 setting to capture outcomes specific to the disease and the cardiorenal protective drug dapagliflozin. We discuss statistical issues of designing trials with an HCE as a primary endpoint and analysis using win odds, including power, sample size, number needed-to-treat calculations, handling of missing data, and visualization of HCEs using maraca plots, as well as computational issues of win statistics in the hce R package and SAS software.