TY - JOUR
T1 - Guidelines for the content of statistical analysis plans in clinical trials
AU - Gamble, Carrol
AU - Krishan, Ashma
AU - Stocken, Deborah
AU - Lewis, Steff
AU - Juszczak, Edmund
AU - Doré, Caroline
AU - Williamson, Paula R.
AU - Altman, Douglas G.
AU - Montgomery, Alan
AU - Lim, Pilar
AU - Berlin, Jesse
AU - Senn, Stephen
AU - Day, Simon
AU - Barbachano, Yolanda
AU - Loder, Elizabeth
N1 - Funding Information:
The need to develop guidance on SAPs was raised during discussion by statisticians attending a UK Clinical Research Collaboration (UKCRC) Registered CTU (Clinical Trials Unit) Statisticians’ Operational Group meeting in November 2012. This group included 46 senior statisticians, each representing their CTU within the network. This wider group was engaged throughout the development process as well as user-testing and piloting. The members of the CTU network, based in the United Kingdom, conduct clinical trials funded by governmental agencies, foundations, and pharmaceutical companies under the remit of the European Medicines Agency, the UK Medicines and Healthcare Products Regulatory Agency (MHRA), and the US Food and Drug Administration. An application for funding was developed and submitted to the Medical Research Council Network of Hubs for Trials Methodology Research in December 2013 and the project started in May 2014. The SAP guidance document was developed with the primary intention of being applicable to the final analyses of later-phase randomized clinical trials addressing the minimum recommended content of a SAP within the context of the following assumptions: 1. The SAP is not a standalone document and should be read in conjunction with the clinical trial protocol; 2. The clinical trial protocol should be consistent with the prin-ciples of the SPIRIT 2013 Statement5; and 3. TheSAPistobeappliedtoacleanorvalidateddatasetforanalysis.
Funding Information:
This work was funded by grant MR/L004933/1-R44 from the UK Medical Research Council Network of Hubs for Trials Methodology Research and supported and endorsed by the UK Clinical Research Collaboration Registered Clinical Trials Unit Network.
Funding Information:
Funding/Support: This work was funded by grant MR/L004933/1-R44 from the UK Medical Research Council Network of Hubs for Trials Methodology Research and supported and endorsed by the UK Clinical Research Collaboration Registered Clinical Trials Unit Network.
Publisher Copyright:
© 2017 American Medical Association. All rights reserved.
PY - 2017/12/19
Y1 - 2017/12/19
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85040083746&partnerID=8YFLogxK
U2 - 10.1001/jama.2017.18556
DO - 10.1001/jama.2017.18556
M3 - Article
C2 - 29260229
AN - SCOPUS:85040083746
VL - 318
SP - 2337
EP - 2343
JO - JAMA - Journal of the American Medical Association
JF - JAMA - Journal of the American Medical Association
SN - 0002-9955
IS - 23
ER -