State of play in individual participant data meta-analyses of randomised trials: Systematic review and consensus-based recommendations

BackgroundIndividual participant data (IPD) meta-analyses obtain, harmonise and synthesise the raw individual-level data from multiple studies, and are increasingly important in an era of data sharing and personalised medicine to inform clinical practice and policy. Objectives(1) Describe the landscape of IPD meta-analysis of randomised trials over time; (2) establish current practice in design, conduct, analysis and reporting for pairwise IPD meta-analysis; and (3) derive recommendations to improve the conduct of and methods for future IPD meta-analyses. DesignPart 1: systematic review of all published IPD meta-analyses of randomised trials; Part 2: in-depth review of current methodological practice for pairwise IPD meta-analysis; and Part 3: adapted nominal group technique to derive consensus recommendations for IPD meta-analysis authors, educators and methodologists. Data sourcesMEDLINE, Embase, and the Cochrane Database of Systematic Reviews (via the Ovid interface). Eligibility criteriaPart 1: all IPD meta-analyses of randomised trials published before February 2024, evaluating intervention effects and based on a systematic search. Part 2: all pairwise IPD meta-analyses from part 1 published between February 2022 and February 2024. Part 3: Selected panel of experienced IPD meta-analysis authors and/or methodologists. ResultsPart 1: We identified 605 eligible IPD meta-analyses published between 1991 and 2024. The number of IPD meta-analyses published per year increased over time until 2019 but has since plateaued to about 60 per year. The most common clinical areas studied were cardiovascular disease (n=113, 19%) and cancer (n=110, 18%). The proportion of IPD meta-analyses published with Cochrane decreased over time from 16% (n=31/196) before 2015 to 3% (n=5/196) between 2021-2024. Part 2: 100 recent pairwise IPD meta-analyses were included in the in-depth review. Most cited PRISMA-IPD (68, 68%) and conducted risk of bias assessments (n=82, 82%), with just under half carrying out subgroup analyses not at risk of aggregation bias (n=36/85, 41%). However, only 33% (n=33) and 29% (n=29) respectively provided a protocol or statistical analysis plan, and only 7% (n=6/82) reported using IPD to inform risk of bias assessments. Part 3: 24 experts participated in a consensus workshop. Key recommendations for improved IPD meta-analyses focused on transparency (prospective registration; published protocols and statistical analysis plans) and maximising value (searching trial registries; obtaining IPD for unpublished evidence; using IPD to address missing data and risk of bias). Methodologists and educators should strengthen dissemination of methods and support capacity building across clinical fields and geographical areas. ConclusionsThe application and methodological quality of IPD meta-analyses of randomised trials has increased in the last decade, but shortcomings remain. Implementing our consensus-based recommendations will ensure future IPD meta-analyses generate better evidence for clinical decision making. Study registrationOpen Science Framework (1) Summary boxesO_ST_ABSWhat is already known on this topicC_ST_ABSO_LIIPD meta-analyses of randomised trials are regularly used to inform clinical policy and practice. C_LIO_LIThey can provide better quality data and enable more thorough and robust analyses than standard aggregate data meta-analyses, but are resource-intensive and can be challenging to conduct, leading to variable methodological quality C_LIO_LIPrevious studies that evaluated the conduct of IPD meta-analyses pre-date several major developments, such as the introduction of the PRISMA-IPD reporting guideline. C_LI What this study addsO_LIThis is the most comprehensive assessment of IPD meta-analyses of randomised trials to date (605 studies), showing an increase in publications over time followed by a recent plateau. C_LIO_LIThe conduct of IPD meta-analysis has improved in recent years including increased use of prospective registration, assessment of risk of bias, appropriate analyses of patient subgroup effects and citing the PRISMA-IPD statement. C_LIO_LIMany shortcomings remain including (i) insufficient pre-specification of methods such as outcomes and analyses, (ii) sub-standard transparency (including publication of protocols, statistical analysis plans and reporting of analyses), and (iii) failure to gain maximum value of IPD (i.e. include unpublished trials, use the IPD to inform risk of bias and trustworthiness assessments, and address missing data appropriately); expert consensus recommendations are provided for how to address these gaps. C_LI