Randomized Clinical Trials Using a Hierarchical Composite Primary End Point

How are hierarchical composite end points (HCEs) currently being used and analyzed as primary end points in randomized clinical trials across medical disciplines? This scoping review of 92 randomized clinical trials (with 79 567 planned participants) using an HCE as a primary end point showed substantial heterogeneity and shortcomings in the planning and analysis of HCEs, as well as the reporting of the hierarchy construction, sample size assumptions, and handling of ties. These findings suggest that the current use of HCEs in randomized clinical trials lacks methodological consistency and transparent reporting, limiting interpretability and comparability across studies and underscoring the need for clear methodological and reporting guidelines.

Corresponding Author: Benjamin Speich, PhD, CLEAR Methods Center, Division of Clinical Epidemiology, Department of Clinical Research, University Hospital Basel, University of Basel, Totengässlein 3, 4051 Basel, Switzerland (benjamin.speich@usb.ch).

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