Definitions, acceptability, limitations, and guidance in the use and reporting of surrogate endpoints in trials: a scoping review

Manyara, A. M. et al. (2023) Definitions, acceptability, limitations, and guidance in the use and reporting of surrogate endpoints in trials: a scoping review. Journal of Clinical Epidemiology, 160, pp. 83-99. (doi: 10.1016/j.jclinepi.2023.06.013) (PMID:37380118)

Abstract

Objective: To synthesise the current literature on the use of surrogate endpoints, including definitions, acceptability, and limitations of surrogate endpoints, and guidance for their design/reporting, into trial reporting items. Study Design and Setting: Literature was identified through searching bibliographic databases (until March 1st, 2022) and grey literature sources (until May 27th, 2022). Data were thematically analysed into four categories: (1) definitions, (2) acceptability, (3) limitations and challenges, and (4) guidance, and synthesised into reporting guidance items. Results: After screening, 90 documents were included: 79% (n=71) had data on definitions, 77% (n=69) on acceptability, 72% (n=65) on limitations and challenges, and 61% (n=55) on guidance. Data were synthesised into 17 potential trial reporting items: explicit statements on the use of surrogate endpoint(s) and justification for their use (items 1-6); methodological considerations, including whether sample size calculations were informed by surrogate validity (items 7-9); reporting of results for composite outcomes containing a surrogate endpoint (item 10); discussion and interpretation of findings (items 11-14); plans for confirmatory studies, collecting data on the surrogate endpoint and target outcome, and data sharing (items 15-16); and informing trial participants about using surrogate endpoints (item 17). Conclusion: The review identified and synthesised items on the use of surrogate endpoints in trials; these will inform the development of the SPIRIT-SURROGATE and CONSORT-SURROGATE extensions.

• Item Type: Articles
• Additional Information: The development of SPIRIT and CONSORT extensions has been funded by the UK Medical Research Council (grant number MR/V038400/1). GSC was supported by Cancer Research UK (programme grant: C49297/A27294). JMB was supported by the NIHR Bristol Biomedical Research centre. SB was supported by Leicester NIHR Biomedical Research Centre.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Ciani, Professor Oriana and Wells, Ms Valerie and Manyara, Dr Anthony and Taylor, Professor Rod
• Authors: Manyara, A. M., Davies, P., Stewart, D., Weir, C. J., Young, A. E., Wells, V., Blazeby, J., Butcher, N. J., Bujkiewicz, S., Chan, A.-W., Collins, G. S., Dawoud, D., Offringa, M., Ouwens, M., Ross, J. S., Taylor, R. S., and Ciani, O.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > MRC/CSO SPHSU
• Journal Name: Journal of Clinical Epidemiology
• Publisher: Elsevier
• ISSN: 0895-4356
• ISSN (Online): 1878-5921
• Published Online: 26 June 2023
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in Journal of Clinical Epidemiology 160: 83-99
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
313399		Reporting of randomised trials using surrogate outcomes: development of extensions to the CONSORT 2010 and SPIRIT 2013 guidance statements	Rodney Stephen Taylor	Medical Research Council (MRC)	MR/V038400/1	HW - MRC/CSO Social and Public Health Sciences Unit