Reporting of surrogate endpoints in randomised controlled trial protocols (SPIRIT-Surrogate): extension checklist with explanation and elaboration

Anthony Muchai Manyara, MRC/CSO Social and Public Health Sciences Unit, School of Health and Wellbeing, University of Glasgow, Glasgow, UK.
Philippa Davies, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Derek Stewart, Patient author, UK.
Christopher J. Weir, Edinburgh Clinical Trials Unit, Usher Institute, University of Edinburgh, Edinburgh, UK.
Amber E. Young, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Jane Blazeby, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Nancy J. Butcher, Child Health Evaluative Sciences, Hospital for Sick Children Research Institute, Toronto, ON, Canada.
Sylwia Bujkiewicz, Biostatistics Research Group, Department of Population Health Sciences, University of Leicester, Leicester, UK.
An-Wen Chan, Women's College Research Institute, Toronto, ON, Canada.
Dalia Dawoud, Science, Evidence, and Analytics Directorate, Science Policy and Research Programme, National Institute for Health and Care Excellence, London, UK.
Martin Offringa, Child Health Evaluative Sciences, Hospital for Sick Children Research Institute, Toronto, ON, Canada.
Mario Ouwens, AstraZeneca, Mölndal, Sweden.
Asbjørn Hróbjartssson, Centre for Evidence-Based Medicine Odense and Cochrane Denmark, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
Alain Amstutz, CLEAR Methods Centre, Division of Clinical Epidemiology, Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland.
Luca Bertolaccini, Department of Thoracic Surgery, IEO, European Institute of Oncology IRCCS, Milan, Italy.
Vito Domenico Bruno, IRCCS Galeazzi-Sant'Ambrogio Hospital, Department of Minimally Invasive Cardiac Surgery, Milan, Italy.
Declan Devane, University of Galway, Galway, Ireland.
Christina D. Faria, Department of Physical Therapy, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Peter B. Gilbert, Fred Hutchinson Cancer Centre, Seattle, WA, USA.
Ray Harris, Patient author, UK.
Marissa Lassere, St George Hospital and School of Population Health, University of New South Wales, Sydney, NSW, Australia.
Lucio Marinelli, Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Genoa, Italy.
Sarah Markham, Patient author, UK.
John H. Powers, George Washington University School of Medicine, Washington, DC, USA.
Yousef Rezaei, Heart Valve Disease Research Centre, Rajaie Cardiovascular Medical and Research Centre, Iran University of Medical Sciences, Tehran, Iran.
Laura Richert, University of Bordeaux, Centre d'Investigation Clinique-Epidémiologie Clinique 1401, Research in Clinical Epidemiology and in Public Health and European Clinical Trials Platform & Development/French Clinical Research Infrastructure Network, Institut National de la Santé et de la Recherche Médicale/Institut Bergonié/Centre Hospitalier Universitaire Bordeaux, Bordeaux, France.
Falk Schwendicke, Charité Universitätsmedizin Berlin, Berlin, Germany.
Larisa G. Tereshchenko, Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Achilles Thoma, McMaster University, Hamilton, ON, Canada.
Alparslan Turan, Department of Outcomes Research, Anaesthesiology Institute, Cleveland Clinic, OH, USA.
Andrew Worrall, Patient author, UK.
Robin Christensen, Section for Biostatistics and Evidence-Based Research, the Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen and Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Odense, Denmark.

Document Type

Journal Article

Publication Date

7-9-2024

Journal

BMJ (Clinical research ed.)

Volume

386

DOI

10.1136/bmj-2023-078525

Abstract

Randomised controlled trials often use surrogate endpoints to substitute for a target outcome (an outcome of direct interest and relevance to trial participants, clinicians, and other stakeholders—eg, all cause mortality) to improve efficiency (through shortened duration of follow-up, reduced sample size, and lower research costs), and for ethical or practical reasons. However, their use has a fundamental limitation in terms of uncertainty of the intervention effect on the target outcome and limited information on potential intervention harms. There have been increasing calls for improved reporting of trial protocols that use surrogate endpoints. This report presents the SPIRIT-Surrogate, an extension of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist, a consensus driven reporting guideline designed for trial protocols using surrogate endpoints as the primary outcome(s). The SPIRIT-Surrogate extension includes nine items modified from the SPIRIT 2013 checklist. The guideline provides examples and explanations for each item. We recommend that all stakeholders (including trial investigators and sponsors, research ethics reviewers, funders, journal editors, and peer reviewers) use this extension in reporting trial protocols that use surrogate endpoints. Its use will allow for improved design of such trials, improved transparency, and interpretation of findings when trials are completed, and ultimately reduced research waste.

Department

Medicine

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