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

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.