Recommendations for evaluating a single surrogate endpoint (REASSurE): consensus based, surrogate evaluation framework with explanation and elaboration

CCBY Open access Research Methods & Reporting Recommendations for evaluating a single surrogate endpoint (REASSurE): consensus based, surrogate evaluation framework with explanation and elaboration BMJ 2026; 394 doi: https://doi.org/10.1136/bmj-2026-100618 (Published 29 September 2026) Cite this as: BMJ 2026;394:e100618 Article Related content Metrics Responses Peer review Wang Pok Lo, medical student12,Stuart G Baker, mathematical statistician3,Luca Bertolaccini, assistant professor and deputy director45,Sylwia Bujkiewicz, professor6,Catey Bunce, honorary professor7,Marc Buyse, chief scientific officer8,Oriana Ciani, associate professor9,Robin Christensen, professor1011,Jane Daniels, professor12,Sara Gandini, group leader13,Tamer A Gheita, professor14,Peter B Gilbert, professor15,Laura Jaeger, associate director16,Dorcas Kareithi, associate statistician1718,Marissa Lassere, conjoint professor19,Nicholas T Longford, director and visiting lecturer2021,Anthony M Manyara, senior research associate22,Koji Oba, professor23,Emily K Roberts, assistant professor24,Rod S Taylor, professor25,Carlos J Toro-Huamanchumo, epidemiologist and research director2627,Steff Lewis, professor (retired)28,Hannah Ensor, senior statistician28,Christopher J Weir, professor28 Author affiliations Correspondence to: C J Weir [email protected] Accepted 11 August 2026 The use of a surrogate endpoint to replace a primary outcome relevant to patients in a clinical trial may allow faster approval of a novel treatment, but at the cost of increased uncertainty about treatment benefit. This risk may be amplified if the surrogate endpoint was inadequately or inappropriately evaluated against the patient relevant outcome. Many components of this evaluation currently lack consensus, including the most important non-statistical factors, the choice of statistical method, and whether numerical thresholds should be used. This paper presents a consensus based, multi-stakeholder framework (REASSurE: Recommendations for Evaluating A Single Surrogate Endpoint) containing a list of mandatory and recommended items for surrogate endpoint evaluation, with guidance on how to assess each item. Statisticians, trials methodologists, regulators, health technology assessment agencies, payers, and clinicians could use the REASSurE framework to achieve a holistic evaluation of a candidate surrogate endpoint, which is vital to ensure that the use of the surrogate endpoint is an appropriate decision.