Hierarchical composite endpoints in clinical trials for multimorbid older adults.

Abstract

Hierarchical composite endpoints (HCEs) has the potential to make clinical trials for multimorbid older adults more relevant. Unlike conventional time-to-first-event analyses-which can give more weight to outcomes of lesser relevance-HCEs rank outcomes by importance to patients and clinicians. This allows priorities such as avoiding hospital stays, maintaining quality of life, and preserving independence to shape trial results, while still accounting for conventional outcomes like mortality. Because they use information from more patients, HCEs can also increase statistical power, which is particularly useful in trials where recruiting older adults is difficult and evidence to guide treatment is limited. However, deciding the order of outcomes requires balancing patient and clinical priorities, and ensuring consistency and regulatory acceptance.