Guidelines for Reporting Outcomes in Trial Protocols

Abstract

ImportanceComplete information in a trial protocol regarding study outcomes is crucial for obtaining regulatory approvals, ensuring standardized trial conduct, reducing research waste, and providing transparency of methods to facilitate trial replication, critical appraisal, accurate reporting and interpretation of trial results, and knowledge synthesis. However, recommendations on what outcome-specific information should be included are diverse and inconsistent. To improve reporting practices promoting transparent and reproducible outcome selection, assessment, and analysis, a need for specific and harmonized guidance as to what outcome-specific information should be addressed in clinical trial protocols exists.ObjectiveTo develop harmonized, evidence- and consensus-based standards for describing outcomes in clinical trial protocols through integration with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 statement.Evidence ReviewUsing the Enhancing the Quality and Transparency of Health Research (EQUATOR) methodological framework, the SPIRIT-Outcomes 2022 extension of the SPIRIT 2013 statement was developed by (1) generation and evaluation of candidate outcome reporting items via consultation with experts and a scoping review of existing guidance for reporting trial outcomes (published within the 10 years prior to March 19, 2018) identified through expert solicitation, electronic database searches of MEDLINE and the Cochrane Methodology Register, gray literature searches, and reference list searches; (2) a 3-round international Delphi voting process (November 2018-February 2019) completed by 124 panelists from 22 countries to rate and identify additional items; and (3) an in-person consensus meeting (April 9-10, 2019) attended by 25 panelists to identify essential items for outcome-specific reporting to be addressed in clinical trial protocols.FindingsThe scoping review and consultation with experts identified 108 recommendations relevant to outcome-specific reporting to be addressed in trial protocols, the majority (72%) of which were not included in the SPIRIT 2013 statement. All recommendations were consolidated into 56 items for Delphi voting; after the Delphi survey process, 19 items met criteria for further evaluation at the consensus meeting and possible inclusion in the SPIRIT-Outcomes 2022 extension. The discussions during and after the consensus meeting yielded 9 items that elaborate on the SPIRIT 2013 statement checklist items and are related to completely defining and justifying the choice of primary, secondary, and other outcomes (SPIRIT 2013 statement checklist item 12) prospectively in the trial protocol, defining and justifying the target difference between treatment groups for the primary outcome used in the sample size calculations (SPIRIT 2013 statement checklist item 14), describing the responsiveness of the study instruments used to assess the outcome and providing details on the outcome assessors (SPIRIT 2013 statement checklist item 18a), and describing any planned methods to account for multiplicity relating to the analyses or interpretation of the results (SPIRIT 2013 statement checklist item 20a).Conclusions and RelevanceThis SPIRIT-Outcomes 2022 extension of the SPIRIT 2013 statement provides 9 outcome-specific items that should be addressed in all trial protocols and may help increase trial utility, replicability, and transparency and may minimize the risk of selective nonreporting of trial results.

Guidelines for Reporting Outcomes in Trial Reports

“…SPIRIT-Outcomes 2022 extension: Additional essential checklist items describing outcome-related trial protocol content that are not covered by the SPIRIT 2013 statement …”

“…The CONSORT-Outcomes 2022 extension provides evidence-and consensus-based guidance for reporting outcomes in published clinical trial reports, extending the CONSORT 2010 statement checklist with 17 additional reporting items and harmonizing reporting recommendations with guidance from the SPIRIT-Outcomes 2022 extension. 17 Alignment across these 2 extension guidelines creates a cohesive continuum of reporting from the trial protocol to the completed trial that will facilitate both the researcher's production of the trial protocol and trial report and, importantly, any assessment of the final report's adherence to the trial protocol. 20 Similar to the CONSORT 2010 statement, 41 the CONSORT-Outcomes 2022 extension applies to the content of the trial report, including the tables and figures and online-only supplementary material.…”

“…The development 15 of the CONSORT-Outcomes 2022 extension occurred in parallel with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT)-Outcomes 2022 extension for clinical trial protocols. 17…”

“…Ethics approval was not required as determined by the research ethics committee at The Hospital for Sick Children. The development of the CONSORT-Outcomes 2022 extension occurred in parallel with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT)–Outcomes 2022 extension for clinical trial protocols …”

“…35,36 SPIRIT-Outcomes 2022 extension: Additional essential checklist items describing outcome-related trial protocol content that are not covered by the SPIRIT 2013 statement. 17 Structural validity: The degree to which the scores of a study instrument (eg, a patient questionnaire or a clinical rating scale) are an adequate reflection of the dimensionality of the domain to be measured. 30 Study instrument: The scale or tool used to make an assessment.…”