Methodological guidance for individual participant data meta-analyses: a systematic review

To systematically identify and synthesize methodological guidance for conducting individual participant data meta-analyses (IPD-MAs) of randomized trials and observational studies, to inform the development of a critical appraisal tool for reports of IPD-MAs.

We searched nine major electronic databases and gray literature sources through June 2025 using a strategy developed with a health sciences librarian. To be eligible, articles had to report empirical, simulation-based, consensus-based, or narrative research and offer guidance on the methodology of IPD-MA. Study selection and data extraction were performed independently by two reviewers. Quality was assessed using tools tailored to study design (eg, Aims, Data generating mechanism, Estimands, Methods, and Performance measures, Risk of Bias in Systematic Reviews, Appraisal of Guidelines for Research & Evaluation using Delphi, Scale for the Assessment of Narrative Review Articles). Extracted guidance was categorized thematically and mapped to appraisal domains.

After screening 14,736 records, we included 141 studies. These encompassed simulation (38%), empirical (21%), and methodological guidance (12%), among others. Key themes included IPD-MA planning, data access and harmonization, analytical strategies, and other statistical issues, as well as reporting. While there was robust guidance for IPD-MA of randomized trials, recommendations for observational studies are sparse. Across all study types, 63% were rated high quality.

This review synthesizes previously fragmented guidance into an integrative synthesis, highlighting best practices and critical domains for evaluating IPD-MAs. These findings formed the evidence base for a Delphi consensus process to develop a dedicated IPD-MA critical appraisal tool.

Meta-analyses often pool published summaries from many studies. That approach can miss important details and introduce bias. An IPD-MA instead reanalyses the original, participant-level data across studies. IPD-MAs are powerful but complex, and practical guidance is scattered, especially for observational studies. We wanted to bring these recommendations together in one place and identify candidate items for a tool to assess the quality of a completed IPD-MA. We systematically searched eight databases from their inception to 2025 to identify papers offering practical guidance on conducting IPD-MAs for health interventions. We organized guidance across the full project life cycle, from planning, finding and accessing data, to preparing and checking data, analyzing results, and reporting. We highlighted where experts broadly agree and where gaps remain. We found 141 relevant papers published between 1995 and 2025. Among these, we identified 25 key topic areas and several smaller subtopics. Many papers covered more than one topic, so we allowed them to appear in multiple categories rather than forcing a single classification. From this mapping, we developed a clear set of recommendations organized around four themes: IPDMA planning; identification and access to studies and individual participant data; methods for meta-analysis; and other special considerations, such as methods for observational studies. We also identified notable gaps for observational IPD-MAs. Our synthesis offers a practical checklist for teams planning or reviewing IPD-MAs. It also lays the groundwork for a consensus-based appraisal tool to help editors, funders, and guideline developers judge quality and improve practice.