Recommendations for evaluating a single surrogate endpoint (REASSurE): consensus based, surrogate evaluation framework with explanation and elaboration
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.
Authors
- Stuart G. Baker (ORCID: https://orcid.org/0000-0001-6759-2838)
- Christopher John Weir (ORCID: https://orcid.org/0000-0002-6494-4903)
- Oriana Ciani (ORCID: https://orcid.org/0000-0002-3607-0508)
- Sara Gandini (ORCID: https://orcid.org/0000-0002-1348-4548)
- Sylwia Bujkiewicz (ORCID: https://orcid.org/0000-0002-3003-9403)
- Robin Christensen (ORCID: https://orcid.org/0000-0002-6600-0631)
- Carlos Jesus Toro-Huamanchumo (ORCID: https://orcid.org/0000-0002-4664-2856)
- Anthony Muchai Manyara (ORCID: https://orcid.org/0000-0001-6276-926X)
- Luca Bertolaccini (ORCID: https://orcid.org/0000-0002-1153-3334)
- Emily Roberts (ORCID: https://orcid.org/0000-0002-5838-9691)
- R. S. Taylor (ORCID: https://orcid.org/0000-0002-3043-6011)
- JANE P. DANIELS (ORCID: https://orcid.org/0000-0003-3324-6771)
- Nicholas T. Longford (ORCID: https://orcid.org/0000-0003-4129-9726)
- Tamer Atef Gheita (ORCID: https://orcid.org/0000-0002-1155-9729)
- Steff Lewis (ORCID: https://orcid.org/0000-0003-1210-2314)
- Wang Pok Lo (ORCID: https://orcid.org/0000-0002-1790-3703)
- Dorcas Njeri Kareithi (ORCID: https://orcid.org/0000-0002-2161-8542)
- Laura Jaeger
- Marc E Buyse (ORCID: https://orcid.org/0000-0002-4559-0994)
- Peter B. Gilbert (ORCID: https://orcid.org/0000-0002-2662-9427)
- Hannah Ensor (ORCID: https://orcid.org/0000-0003-3052-7287)
- Marissa Nichole Lassere
- Koji Oba
- Catey Bunce
Institutions
- University of Iowa (US)
- Center for Drug Evaluation and Research (US)
- University of Nottingham (GB)
- Cairo University (EG)
- University of Leicester (GB)
- University of Southern Denmark (DK)
- SGH Warsaw School of Economics (PL)
- University of Milan (IT)
- Universidad San Ignacio de Loyola (PE)
- Frederiksberg Hospital (DK)
- Odense University Hospital (DK)
- Independent Sector (US)
- UNSW Sydney (AU)
- University of Bristol (GB)
- Fred Hutch Cancer Center (US)
- London School of Hygiene & Tropical Medicine (GB)
- International Drug Development Institute (Belgium) (BE)
- St George Hospital (AU)
- Glasgow Centre for Population Health (GB)
- OBEMET Center for Obesity and Metabolic Health (PE)
- International Centre for Eye Health (GB)
- European Institute of Oncology (IT)
- Bocconi University (IT)
- The University of Tokyo (JP)
- University of Newcastle Australia (AU)
- Newcastle University (GB)
- University of Edinburgh (GB)
Publication Details
- Journal
- BMJ
- Published
- 2026-09-29
- DOI
- https://doi.org/10.1136/bmj-2026-100618
- Primary Topic
- Health Systems, Economic Evaluations, Quality of Life
- Type
- article
- Field-Weighted Citation Impact
- 0.00