Comparing different methods for analysing hierarchical composite endpoints: two illustrative case studies with post hoc analyses of the BALANCE (Bacteraemia Antibiotic Length Actually Needed for Clinical Effectiveness) and CAMERA2 (Combination Antibiotics for methicillin-resistant Staphylococcus aureus) randomized clinical trials

Abstract

Objectives Hierarchical composite endpoints (HCEs) are increasingly being used in infectious disease research. In this paper, we illustrate different methods for analysing HCEs in post hoc analyses of the Bacteraemia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE) and Combination Antibiotics for MEthicillin Resistant Staphylococcus aureus (CAMERA2) clinical trials. Methods We constructed post hoc HCEs for each trial by combining clinical efficacy and safety outcomes: (a) mortality, relapse of bacteraemia, and antibiotic adverse events for BALANCE, and (b) mortality, primary treatment failure, infectious complications, and antibiotic adverse events for CAMERA2. For both..