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

<p>Objective</p> <p>To synthesize the current literature on the use of surrogate end points, including definitions, acceptability, and limitations of surrogate end points and guidance for their design/reporting, into trial reporting items.</p> <p><br></p> <p>Study Design and Setting</p> <p>Literature was identified through searching bibliographic databases (until March 1, 2022) and gray literature sources (until May 27, 2022). Data were thematically analyzed into four categories: (1) definitions, (2) acceptability, (3) limitations and challenges, and (4) guidance, and synthesized into reporting guidance items.</p> <p><br></p> <p>Results</p> <p>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 synthesized into 17 potential trial reporting items: explicit statements on the use of surrogate end point(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 end point (item 10); discussion and interpretation of findings (items 11–14); plans for confirmatory studies, collecting data on the surrogate end point and target outcome, and data sharing (items 15–16); and informing trial participants about using surrogate end points (item 17).</p> <p><br></p> <p>Conclusion</p> <p>The review identified and synthesized items on the use of surrogate end points in trials; these will inform the development of the Standard Protocol Items: Recommendations for Interventional Trials–SURROGATE and Consolidated Standards of Reporting Trials–SURROGATE extensions.</p>