Definitions, acceptability, limitations, and guidance in the use and reporting of surrogate end points in trials: a scoping review
- PMID: 37380118
- DOI: 10.1016/j.jclinepi.2023.06.013
Definitions, acceptability, limitations, and guidance in the use and reporting of surrogate end points in trials: a scoping review
Abstract
Objective: 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.
Study design and setting: 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.
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 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).
Conclusion: 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.
Keywords: CONSORT-Surrogate; Design; Protocols; Randomized controlled trials; Reporting guidance; SPIRIT-Surrogate; Scoping review; Surrogate end points; Validation.
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of competing interest Sylwia Bujkiewicz is a member of the NICE Decision Support Unit and NICE Guidelines Technical Support Unit. She has served as a paid consultant, providing methodological advice, to NICE, Roche, IQVIA, and RTI Health Solutions, received payments for educational events from Roche, and has received research funding from European Federation of Pharmaceutical Industries and Associations and Johnson & Johnson. Mario Ouwens works for and has shares in AstraZeneca. Joseph Ross is an Associate Editor at BMJ and co-founder (unpaid) of medRxiv; research support through Yale University from Johnson and Johnson to develop methods of clinical trial data sharing, from the Medical Device Innovation Consortium as part of the National Evaluation System for Health Technology, from the Food and Drug Administration for the Yale-Mayo Clinic Center for Excellence in Regulatory Science and Innovation program (U01FD005938); from the Agency for Healthcare Research and Quality (R01HS022882); from the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) (R01HS025164, R01HL144644); and from the Laura and John Arnold Foundation to establish the Good Pharma Scorecard at Bioethics International; expert witness at the request of Relator's attorneys, the Greene Law Firm, in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen Inc. Nancy Butcher has received consulting fees from Nobias Therapeutics, Inc.
