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

Anthony Muchai Manyara; Philippa Davies; Derek Stewart; Christopher J. Weir; Amber E. Young; Jane Blazeby; Nancy J. Butcher; Sylwia Bujkiewicz; An Wen Chan; Dalia Dawoud; Martin Offringa; Mario Ouwens; Asbjørn Hróbjartssson; Alain Amstutz; Luca Bertolaccini; Vito Domenico Bruno; Declan Devane; Christina D.C.M. Faria; Peter B. Gilbert; Ray Harris; Marissa Lassere; Lucio Marinelli; Sarah Markham; John H. Powers; Yousef Rezaei; Laura Richert; Falk Schwendicke; Larisa G. Tereshchenko; Achilles Thoma; Alparslan Turan; Andrew Worrall; Robin Christensen; Gary S. Collins; Joseph S. Ross; Rod S. Taylor; Oriana Ciani

doi:10.1136/bmj-2023-078525

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

Anthony Muchai Manyara, Philippa Davies, Derek Stewart, Christopher J. Weir, Amber E. Young, Jane Blazeby, Nancy J. Butcher, Sylwia Bujkiewicz, An Wen Chan, Dalia Dawoud, Martin Offringa, Mario Ouwens, Asbjørn Hróbjartssson, Alain Amstutz, Luca Bertolaccini, Vito Domenico Bruno, Declan Devane, Christina D.C.M. Faria, Peter B. Gilbert, Ray HarrisMarissa Lassere, Lucio Marinelli, Sarah Markham, John H. Powers, Yousef Rezaei, Laura Richert, Falk Schwendicke, Larisa G. Tereshchenko, Achilles Thoma, Alparslan Turan, Andrew Worrall, Robin Christensen, Gary S. Collins, Joseph S. Ross, Rod S. Taylor, Oriana Ciani

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6 Scopus citations

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.

Original language	English
Article number	e078525
Journal	The BMJ
DOIs	https://doi.org/10.1136/bmj-2023-078525
State	Published - Jul 9 2024

Funding

Funding: The research was funded as part of the development of SPIRIT and CONSORT extensions by the UK Medical Research Council (grant MR/V038400/1). GSC was supported by Cancer Research UK (programme grant C49297/A27294). JB was supported by the NIHR Bristol Biomedical Research centre. SB was supported by the UK Medical Research Council (MR/T025166/1) and Leicester NIHR Biomedical Research Centre. AA receives his salary from the Research Fund Junior Researchers of the University of Basel. RC acknowledges that the Section for Biostatistics and Evidence-Based Research (Parker Institute, Bispebjerg and Frederiksberg Hospital) is supported by core grants. CDCMF receives research productivity fellowships from the Oak Foundation (OCAY-18-774-OFIL) and National Council for Scientific and Technological Development (CNPq/Brazil grant 08516/2021-4). The views expressed in this article are those of the authors and not their employers or funders. The funders had no role in the design and conduct of the study; the data collection, management, analysis, and interpretation; the drafting, review, or approval of the manuscript; or the decision to submit the manuscript for publication. This article reflects personal the views of the authors, the Delphi participants, and the consensus meeting delegates, and may not represent the views of the broader stakeholder groups, authors\u2019 institutions, or other affiliations.

Funders	Funder number
core grants
NIHR Bristol Biomedical Research Centre
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Section for Biostatistics and Evidence-Based Research
Universität Basel
NIHR Leicester Biomedical Research Centre
Brazil	08516/2021-4
Cancer Research UK	C49297/A27294
Medical Research Council	MR/T025166/1, MR/V038400/1
Oak Foundation	OCAY-18-774-OFIL

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Manyara, A. M., Davies, P., Stewart, D., Weir, C. J., Young, A. E., Blazeby, J., Butcher, N. J., Bujkiewicz, S., Chan, A. W., Dawoud, D., Offringa, M., Ouwens, M., Hróbjartssson, A., Amstutz, A., Bertolaccini, L., Bruno, V. D., Devane, D., Faria, C. D. C. M., Gilbert, P. B., ... Ciani, O. (2024). Reporting of surrogate endpoints in randomised controlled trial protocols (SPIRIT-Surrogate): extension checklist with explanation and elaboration. The BMJ, Article e078525. https://doi.org/10.1136/bmj-2023-078525

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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.",

author = "Manyara, {Anthony Muchai} and Philippa Davies and Derek Stewart and Weir, {Christopher J.} and Young, {Amber E.} and Jane Blazeby and Butcher, {Nancy J.} and Sylwia Bujkiewicz and Chan, {An Wen} and Dalia Dawoud and Martin Offringa and Mario Ouwens and Asbj{\o}rn Hr{\'o}bjartssson and Alain Amstutz and Luca Bertolaccini and Bruno, {Vito Domenico} and Declan Devane and Faria, {Christina D.C.M.} and Gilbert, {Peter B.} and Ray Harris and Marissa Lassere and Lucio Marinelli and Sarah Markham and Powers, {John H.} and Yousef Rezaei and Laura Richert and Falk Schwendicke and Tereshchenko, {Larisa G.} and Achilles Thoma and Alparslan Turan and Andrew Worrall and Robin Christensen and Collins, {Gary S.} and Ross, {Joseph S.} and Taylor, {Rod S.} and Oriana Ciani",

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Manyara, AM, Davies, P, Stewart, D, Weir, CJ, Young, AE, Blazeby, J, Butcher, NJ, Bujkiewicz, S, Chan, AW, Dawoud, D, Offringa, M, Ouwens, M, Hróbjartssson, A, Amstutz, A, Bertolaccini, L, Bruno, VD, Devane, D, Faria, CDCM, Gilbert, PB, Harris, R, Lassere, M, Marinelli, L, Markham, S, Powers, JH, Rezaei, Y, Richert, L, Schwendicke, F, Tereshchenko, LG, Thoma, A, Turan, A, Worrall, A, Christensen, R, Collins, GS, Ross, JS, Taylor, RS & Ciani, O 2024, 'Reporting of surrogate endpoints in randomised controlled trial protocols (SPIRIT-Surrogate): extension checklist with explanation and elaboration', The BMJ. https://doi.org/10.1136/bmj-2023-078525

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T1 - Reporting of surrogate endpoints in randomised controlled trial protocols (SPIRIT-Surrogate)

T2 - extension checklist with explanation and elaboration

AU - Manyara, Anthony Muchai

AU - Davies, Philippa

AU - Stewart, Derek

AU - Weir, Christopher J.

AU - Young, Amber E.

AU - Blazeby, Jane

AU - Butcher, Nancy J.

AU - Bujkiewicz, Sylwia

AU - Chan, An Wen

AU - Dawoud, Dalia

AU - Offringa, Martin

AU - Ouwens, Mario

AU - Hróbjartssson, Asbjørn

AU - Amstutz, Alain

AU - Bertolaccini, Luca

AU - Bruno, Vito Domenico

AU - Devane, Declan

AU - Faria, Christina D.C.M.

AU - Gilbert, Peter B.

AU - Harris, Ray

AU - Lassere, Marissa

AU - Marinelli, Lucio

AU - Markham, Sarah

AU - Powers, John H.

AU - Rezaei, Yousef

AU - Richert, Laura

AU - Schwendicke, Falk

AU - Tereshchenko, Larisa G.

AU - Thoma, Achilles

AU - Turan, Alparslan

AU - Worrall, Andrew

AU - Christensen, Robin

AU - Collins, Gary S.

AU - Ross, Joseph S.

AU - Taylor, Rod S.

AU - Ciani, Oriana

PY - 2024/7/9

Y1 - 2024/7/9

N2 - 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.

AB - 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.

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JO - The BMJ

JF - The BMJ

M1 - e078525

ER -

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

Abstract

Funding

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