Evaluating the use of hierarchical composite endpoints in pediatric cancer supportive care clinical trials: Illustrative examples from two multi-center phase-III randomized clinical trials

Collier WH, Zobeck M, Esbenshade AJ, Dvorak CC, Sung L, Freyer D, Alexander S, Orgel E, Ullrich NJ, Prudowsky Z, Fisher B, Elgarten CW. Evaluating the use of hierarchical composite endpoints in pediatric cancer supportive care clinical trials: Illustrative examples from two multi-center phase-III randomized clinical trials. medRxiv [Preprint]. 2026 Jan 23:2026.01.20.26344064. doi: 10.64898/2026.01.20.26344064. PMID: 41659071; PMCID: PMC12879711.

Pediatric supportive care trials frequently rely on analyses of multiple clinically relevant outcomes, posing challenges for overall trial interpretation. Hierarchical composite endpoints (HCEs) rank relevant outcomes by prespecified clinical importance and offer potential advantages such as harmonizing trial conclusions.