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. 2022 Oct 11;12(10):e064304.
doi: 10.1136/bmjopen-2022-064304.

Protocol for the development of SPIRIT and CONSORT extensions for randomised controlled trials with surrogate primary endpoints: SPIRIT-SURROGATE and CONSORT-SURROGATE

Anthony Muchai Manyara  1 , Philippa Davies  2 , Derek Stewart  3 , Christopher J Weir  4 , Amber Young  2 , Nancy J Butcher  5   6 , Sylwia Bujkiewicz  7 , An-Wen Chan  8   9 , Gary S Collins  10 , Dalia Dawoud  11 , Martin Offringa  6 , Mario Ouwens  12 , Joseph S Ross  13   14 , Rod S Taylor  15   16 , Oriana Ciani  17
Affiliations

Protocol for the development of SPIRIT and CONSORT extensions for randomised controlled trials with surrogate primary endpoints: SPIRIT-SURROGATE and CONSORT-SURROGATE

Anthony Muchai Manyara et al. BMJ Open. .

Abstract

Introduction: Randomised controlled trials (RCTs) may use surrogate endpoints as substitutes and predictors of patient-relevant/participant-relevant final outcomes (eg, survival, health-related quality of life). Translation of effects measured on a surrogate endpoint into health benefits for patients/participants is dependent on the validity of the surrogate; hence, more accurate and transparent reporting on surrogate endpoints is needed to limit misleading interpretation of trial findings. However, there is currently no explicit guidance for the reporting of such trials. Therefore, we aim to develop extensions to the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) and CONSORT (Consolidated Standards of Reporting Trials) reporting guidelines to improve the design and completeness of reporting of RCTs and their protocols using a surrogate endpoint as a primary outcome.

Methods and analysis: The project will have four phases: phase 1 (literature reviews) to identify candidate reporting items to be rated in a Delphi study; phase 2 (Delphi study) to rate the importance of items identified in phase 1 and receive suggestions for additional items; phase 3 (consensus meeting) to agree on final set of items for inclusion in the extensions and phase 4 (knowledge translation) to engage stakeholders and disseminate the project outputs through various strategies including peer-reviewed publications. Patient and public involvement will be embedded into all project phases.

Ethics and dissemination: The study has received ethical approval from the University of Glasgow College of Medical, Veterinary and Life Sciences Ethics Committee (project no: 200210051). The findings will be published in open-access peer-reviewed publications and presented in conferences, meetings and relevant forums.

Keywords: general medicine (see internal medicine); protocols & guidelines; public health; statistics & research methods.

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Conflict of interest statement

Competing interests: Sylwia Bujkiewicz has served as a paid consultant, providing methodological advice, to NICE, Roche and RTI Health Solutions, received payments for educational events from Roche and has received research funding from European Federation of Pharmaceutical Industries and Associations (EEPIA) and Johnson and Johnson. Mario Ouwens works for and has shares in AstraZeneca. Dr Joseph S Ross is an Associate Editor at BMJ and co-founder (unpaid) of medRxiv; Dr Ross currently receives 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 (NEST), from the Food and Drug Administration for the Yale-Mayo Clinic Centre for Excellence in Regulatory Science and Innovation (CERSI) programme (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 and R01HL144644), and from the Laura and John Arnold Foundation to establish the Good Pharma Scorecard at Bioethics International; in addition, Dr Ross is an 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.

Figures

Figure 1
Figure 1
Project phases, timelines, activities in each phase (middle), with integrated knowledge translation (left) and patient and public involvement (right). Timelines include preparatory work before start of each phase. Adapted from Kwakkenbos et al. RCTs, Randomised Controlled Trials.
See this image and copyright information in PMC

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