Consensus Statement for Protocols of Factorial Randomized Trials: Extension of the SPIRIT 2013 Statement

Kahan, Brennan C.; Hall, Sophie S.; Beller, Elaine M.; Birchenall, Megan; Elbourne, Diana; Juszczak, Edmund; Little, Paul; Fletcher, John; Golub, Robert M.; Goulao, Beatriz; Hopewell, Sally; Islam, Nazrul; Zwarenstein, Merrick; Chan, An-Wen; Montgomery, Alan A.

Abstract

Importance

Trial protocols outline a trial’s objectives as well as the methods (design, conduct, and analysis) that will be used to meet those objectives, and transparent reporting of trial protocols ensures objectives are clear and facilitates appraisal regarding the suitability of study methods. Factorial trials, in which 2 or more interventions are assessed in the same set of participants, have unique methodological considerations. However, no extension of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 Statement, which provides guidance on reporting of trial protocols, for factorial trials is available.

Objective

To develop a consensus-based extension to the SPIRIT 2013 Statement for factorial trials.

Evidence

Review The SPIRIT extension for factorial trials was developed using the Enhancing the Quality and Transparency of Health Research (EQUATOR) methodological framework. First, a list of reporting recommendations was generated using a scoping review of methodological articles identified using a MEDLINE search (inception to May 2019), which was supplemented with relevant articles from the personal collections of the authors. Second, a 3-round Delphi survey (January to June 2022, completed by 104 panelists from 14 countries) was conducted to assess the importance of items and identify additional recommendations. Third, a hybrid consensus meeting was held, attended by 15 panelists to finalize selection and wording of the checklist.

Findings

This SPIRIT extension for factorial trials modified 9 of the 33 items in the SPIRIT 2013 checklist. Key reporting recommendations were that the rationale for using a factorial design should be provided, including whether an interaction is hypothesized; the treatment groups that will form the main comparisons should be identified; and statistical methods for each main comparison should be provided, including how interactions will be assessed.

Conclusions and Relevance

In this consensus statement, 9 factorial-specific items were provided that should be addressed in all protocols of factorial trials to increase the trial’s utility and transparency.

• Journal Article Type: Article
• Acceptance Date: Oct 21, 2023
• Online Publication Date: Dec 5, 2023
• Publication Date: Dec 5, 2023
• Deposit Date: Dec 6, 2023
• Publicly Available Date: Dec 6, 2023
• Journal: JAMA Network Open
• Electronic ISSN: 2574-3805
• Publisher: American Medical Association
• Peer Reviewed: Peer Reviewed
• Volume: 6
• Issue: 12
• Article Number: e2346121
• DOI: https://doi.org/10.1001/jamanetworkopen.2023.46121
• Keywords: General Medicine
• Public URL: https://nottingham-repository.worktribe.com/output/28143042
• Publisher URL: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2812568