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.
Keywords: Surrogate endpoints; randomised controlled trials; protocols; reporting guidance; scoping review
What is new?
Key findings
•From 90 documents (peer-reviewed and grey literature), we categorised findings into four themes about the use of surrogate endpoints in trials: definitions; acceptability; limitations and challenges to use; and advice and guidance in design and reporting of trials.
•Data from these themes were synthesised into 17 items for designing and reporting of trials using surrogate endpoints as primary outcomes.
What this adds to what is known
•Current reviews on surrogate endpoints in trials have been narrative in nature and restricted to specific clinical/health areas.
•There is no published comprehensive guidance for reporting trials using surrogate endpoints as primary outcomes.
What is the implication and what should change now?
•The items synthesised in this scoping review will inform the development of the SPIRIT-SURROGATE and CONSORT-SURROGATE extensions.
•Implementation of these extensions by trialists, journal editors and peer reviewers can lead to improved reporting of trials and their protocols that use surrogate endpoints as primary outcomes.
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.
Keywords: Surrogate endpoints; randomised controlled trials; protocols; reporting guidance; scoping review
What is new?
Key findings
•From 90 documents (peer-reviewed and grey literature), we categorised findings into four themes about the use of surrogate endpoints in trials: definitions; acceptability; limitations and challenges to use; and advice and guidance in design and reporting of trials.
•Data from these themes were synthesised into 17 items for designing and reporting of trials using surrogate endpoints as primary outcomes.
What this adds to what is known
•Current reviews on surrogate endpoints in trials have been narrative in nature and restricted to specific clinical/health areas.
•There is no published comprehensive guidance for reporting trials using surrogate endpoints as primary outcomes.
What is the implication and what should change now?
•The items synthesised in this scoping review will inform the development of the SPIRIT-SURROGATE and CONSORT-SURROGATE extensions.
•Implementation of these extensions by trialists, journal editors and peer reviewers can lead to improved reporting of trials and their protocols that use surrogate endpoints as primary outcomes.
| Original language | English |
|---|---|
| Pages (from-to) | 83-99 |
| Number of pages | 17 |
| Journal | Journal of Clinical Epidemiology |
| Volume | 160 |
| Early online date | 26 Jun 2023 |
| DOIs | |
| Publication status | Published - 1 Aug 2023 |
Bibliographical note
Funding Information:Funding: The development of SPIRIT and CONSORT extensions has been funded by the UK Medical Research Council (grant number MR/V038400/1 ). G.S.C. was supported by Cancer Research UK (program grant: C49297/A27294 ). J.M.B. was supported by the NIHR Bristol Biomedical Research center. S.B. was supported by Leicester NIHR Biomedical Research Centre. The funders had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the review for publication.
Publisher Copyright:
© 2023 The Author(s)