Avoidable waste of research related to outcome planning and reporting in clinical trials

Background: Recent systematic reviews have demonstrated wide variations on outcome measure selection and outcome reporting in trials on surgical treatments for anterior, apical and mesh prolapse surgery. A systematic review of reported outcomes and outcome measures in posterior compartment vaginal prolapse interventions is highly warranted in the process of developing core outcome sets. Objective: To evaluate outcome and outcome measures reporting in posterior prolapse surgical trials. Search strategy: We searched MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL). Selection criteria: Randomized trials evaluating the efficacy and safety of different surgical interventions for posterior compartment vaginal prolapse.Data collection and analysis: Two researchers independently assessed studies for inclusion, evaluated methodological quality, and extracted relevant data. Methodological quality, outcome reporting quality and publication characteristics were evaluated.

Poorly designed wound trials that generate knowledge that does not inform clinical practice constitute an example of research waste that undermines evidence-based healthcare. Well-designed trials that generate clinically relevant and robust knowledge are integral to improving health nationwide and achieving universal health coverage. This paper critically analyses the existing challenges associated with improving trials as well as how these challenges can be overcome through a research community of practice, such as the Wounds Research Network (WReN). Although a wide range of people have a stake in improving wound trials, they often belong to different social or professional groups that can make collaborative work challenging. In the UK, WReN demonstrates how a unifying national research community of practice can help people work together to design and conduct studies that generate knowledge that may help improve patient care. Key Message • Communities of practice such as the WReN are a useful resource for improving wound trials to generate knowledge that informs clinical practice and contributes to the establishment of universal health coverage.

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.