Guidelines for the Content of Statistical Analysis Plans in Clinical Trials

Gamble, Carrol; Krishan, Ashma; Stocken, Deborah; Lewis, Steff; Juszczak, Edmund; Dor�, Caroline; Williamson, Paula R.; Altman, Douglas G.; Montgomery, Alan; Lim, Pilar; Berlin, Jesse; Senn, Stephen; Day, Simon; Barbachano, Yolanda; Loder, Elizabeth

Abstract

© 2017 American Medical Association. All rights reserved. IMPORTANCE While guidance on statistical principles for clinical trials exists, there is an absence of guidance covering the required content of statistical analysis plans (SAPs) to support transparency and reproducibility. OBJECTIVE To develop recommendations for a minimum set of items that should be addressed in SAPs for clinical trials, developed with input from statisticians, previous guideline authors, journal editors, regulators, and funders. DESIGN Funders and regulators (n = 39) of randomized trials were contacted and the literature was searched to identify existing guidance; a survey of current practice was conducted across the network of UK Clinical Research Collaboration–registered trial units (n = 46, 1 unit had 2 responders) and a Delphi survey (n = 73 invited participants) was conducted to establish consensus on SAPs. The Delphi survey was sent to statisticians in trial units who completed the survey of current practice (n = 46), CONSORT (Consolidated Standards of Reporting Trials) and SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guideline authors (n = 16), pharmaceutical industry statisticians (n = 3), journal editors (n = 9), and regulators (n = 2) (3 participants were included in 2 groups each), culminating in a consensus meeting attended by experts (N = 12) with representatives from each group. The guidance subsequently underwent critical review by statisticians from the surveyed trial units and members of the expert panel of the consensus meeting (N = 51), followed by piloting of the guidance document in the SAPs of 5 trials. FINDINGS No existing guidance was identified. The registered trials unit survey (46 responses) highlighted diversity in current practice and confirmed support for developing guidance. The Delphi survey (54 of 73, 74% participants completing both rounds) reached consensus on 42% (n = 46) of 110 items. The expert panel (N = 12) agreed that 63 items should be included in the guidance, with an additional 17 items identified as important but may be referenced elsewhere. Following critical review and piloting, some overlapping items were combined, leaving 55 items. CONCLUSIONS AND RELEVANCE Recommendations are provided for a minimum set of items that should be addressed and included in SAPs for clinical trials. Trial registration, protocols, and statistical analysis plans are critically important in ensuring appropriate reporting of clinical trials.

Citation

Gamble, C., Krishan, A., Stocken, D., Lewis, S., Juszczak, E., Doré, C., Williamson, P. R., Altman, D. G., Montgomery, A., Lim, P., Berlin, J., Senn, S., Day, S., Barbachano, Y., & Loder, E. (2017). Guidelines for the Content of Statistical Analysis Plans in Clinical Trials. Journal of the American Medical Association, 318(23), 2337-2343. https://doi.org/10.1001/jama.2017.18556

• Journal Article Type: Article
• Acceptance Date: Nov 7, 2017
• Online Publication Date: Dec 19, 2017
• Publication Date: Dec 19, 2017
• Deposit Date: Sep 25, 2020
• Publicly Available Date: Mar 10, 2021
• Journal: JAMA
• Print ISSN: 0098-7484
• Electronic ISSN: 1538-3598
• Publisher: American Medical Association
• Peer Reviewed: Not Peer Reviewed
• Volume: 318
• Issue: 23
• Pages: 2337-2343
• DOI: https://doi.org/10.1001/jama.2017.18556
• Keywords: General Medicine
• Public URL: https://nottingham-repository.worktribe.com/output/4924647
• Publisher URL: https://jamanetwork.com/journals/jama/fullarticle/2666509
• Additional Information: © 2017 American Medical Association. All rights reserved.