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

Wang Lo; Stuart Baker; Bertolaccini Luca; Bujkiewicz Sylwia; Bunce Catey; Marc Buyse; Ciani Oriana; Robin Christensen; Jane Daniels; Sara Gandini; Tamer Gheita; Peter Gilbert; Laura Jaeger; Kareithi Dorcas; Lassere Marissa; Nicholas Longford; Anthony Manyara; Oba Koji; Emily Roberts; Rod Taylor; Carlos Toro-Huamanchumo; Lewis Steff; Hannah Ensor; Christopher Weir

doi:10.1136/bmj-2026-100618

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

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

Wang Lo, Stuart Baker, Bertolaccini Luca, Bujkiewicz Sylwia, Bunce Catey, Marc Buyse, Ciani Oriana, Robin Christensen, Jane Daniels, Sara Gandini, …

BMJ. British medical journal (Clinical research ed.), Vol.394, e100618

09/29/2026

DOI: 10.1136/bmj-2026-100618

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Abstract

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.

Clinical Trials

Technology Assessment

Drug development

Health technology assessment

Patients

Stakeholders

Statistical analysis

Statistical methods

Validity

Working groups

Details

Title: Subtitle: Recommendations for evaluating a single surrogate endpoint (REASSurE): consensus based, surrogate evaluation framework with explanation and elaboration
Creators: Wang Lo - Glasgow Centre for Population Health
Stuart Baker - Independent Sector
Bertolaccini Luca
Bujkiewicz Sylwia
Bunce Catey
Marc Buyse - International Drug Development Institute (Belgium)
Ciani Oriana
Robin Christensen - University of Southern Denmark
Jane Daniels - University of Nottingham
Sara Gandini - European Institute of Oncology
Tamer Gheita - Cairo University
Peter Gilbert - Fred Hutch Cancer Center
Laura Jaeger - Center for Drug Evaluation and Research
Kareithi Dorcas
Lassere Marissa
Nicholas Longford - SGH Warsaw School of Economics
Anthony Manyara - University of Bristol
Oba Koji
Emily Roberts - University of Iowa
Rod Taylor - University of Glasgow
Carlos Toro-Huamanchumo - Universidad San Ignacio de Loyola
Lewis Steff
Hannah Ensor - University of Edinburgh
Christopher Weir - University of Edinburgh
Resource Type: Journal article
Publication Details: BMJ. British medical journal (Clinical research ed.), Vol.394, e100618
DOI: 10.1136/bmj-2026-100618
eISSN: 1756-1833
Publisher: BMJ Publishing Group LTD
Language: English
Date published: 09/29/2026
Academic Unit: Biostatistics
Record Identifier: 9985237505302771

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