While there is some consensus on methods for investigating statistical and methodological heterogeneity, little attention has been paid to clinical aspects of heterogeneity. The objective of this study is to summarize and collate suggested methods for investigating clinical heterogeneity in systematic reviews. We searched databases (Medline, EMBASE, CINAHL, Cochrane Library, and CONSORT, to December 2010) and reference lists and contacted experts to identify resources providing suggestions for investigating clinical heterogeneity between controlled clinical trials included in systematic reviews. We extracted recommendations, assessed resources for risk of bias, and collated the recommendations. One hundred and one resources were collected, including narrative reviews, methodological reviews, statistical methods papers, and textbooks. These resources generally had a low risk of bias, but there was minimal consensus among them. Resources suggested that planned investigations of clinical heterogeneity should be made explicit in the protocol of the review; clinical experts should be included on the review team; a set of clinical covariates should be chosen considering variables from the participant level, intervention level, outcome level, research setting, or others unique to the research question; covariates should have a clear scientific rationale; there should be a sufficient number of trials per covariate; and results of any such investigations should be interpreted with caution. Though the consensus was minimal, there were many recommendations in the literature for investigating clinical heterogeneity in systematic reviews. Formal recommendations for investigating clinical heterogeneity in systematic reviews of controlled trials are required.

Although comprehensive and widespread guidelines on how to conduct systematic reviews of outcome measurement instruments (OMIs) exist, for example from the COSMIN (COnsensus-based Standards for the selection of health Measurement INstruments) initiative, key information is often missing in published reports. This article describes the development of an extension of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guideline: PRISMA-COSMIN for OMIs 2024. The development process followed the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) guidelines and included a literature search, expert consultations, a Delphi study, a hybrid workgroup meeting, pilot testing, and an end-of-project meeting, with integrated patient/public involvement. From the literature and expert consultation, 49 potentially relevant reporting items were identified. Round 1 of the Delphi study was completed by 103 panelists, whereas round 2 and 3 were completed by 78 panelists. After 3 rounds, agreement (≥67%) on inclusion and wording was reached for 44 items. Eleven items without consensus for inclusion and/or wording were discussed at a workgroup meeting attended by 24 participants. Agreement was reached for the inclusion and wording of 10 items, and the deletion of 1 item. Pilot testing with 65 authors of OMI systematic reviews further improved the guideline through minor changes in wording and structure, finalized during the end-of-project meeting. The final checklist to facilitate the reporting of full systematic review reports contains 54 (sub)items addressing the review's title, abstract, plain language summary, open science, introduction, methods, results, and discussion. Thirteen items pertaining to the title and abstract are also included in a separate abstract checklist, guiding authors in reporting for example conference abstracts. PRISMA-COSMIN for OMIs 2024 consists of two checklists (full reports; abstracts), their corresponding explanation and elaboration documents detailing the rationale and examples for each item, and a data flow diagram. PRISMA-COSMIN for OMIs 2024 can improve the reporting of systematic reviews of OMIs, fostering their reproducibility and allowing end-users to appraise the quality of OMIs and select the most appropriate OMI for a specific application. NOTE: This paper was jointly developed by Journal of Clinical Epidemiology, Quality of Life Research, Journal of Patient Reported Outcomes, Health and Quality of Life Outcomes and jointly published by Elsevier Inc, Springer Nature Switzerland AG, and BioMed Central Ltd., part of Springer Nature. The articles are identical except for minor stylistic and spelling differences in keeping with each journal's style. Either citation can be used when citing this article.

Critics of systematic reviews have argued that these studies often fail to inform clinical decision making because their results are far too general, that the data are sparse, such that findings cannot be applied to individual patients or for other decision making. While there is some consensus on methods for investigating statistical and methodological heterogeneity, little attention has been paid to clinical aspects of heterogeneity. Clinical heterogeneity, true effect heterogeneity, can be defined as variability among studies in the participants, the types or timing of outcome measurements, and the intervention characteristics. The objective of this project was to develop recommendations for investigating clinical heterogeneity in systematic reviews.