SynthesisJAMA network open2026
Effect Modification Analyses in Individual Participant Data Meta-Analyses: A Systematic Review.
Synthesis in JAMA network open, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Importance: How often effect modification analyses in individual participant data meta-analyses (IPDMAs) are prespecified and consistently reported in protocols and corresponding reports remains unclear. Objective: To investigate the planning of effect modification analyses in IPDMA protocols and evaluate their concordance with corresponding published reports. Evidence Review: In this systematic review, Medline, Embase, the Cochrane Database of Systematic Reviews, and PROSPERO were searched for protocols of IPDMAs of randomized clinical trials from database inception until December 31, 2021, and their corresponding published study reports until January 31, 2024. Paired reviewers independently identified eligible protocols and reports and extracted data. Planning and reporting characteristics of effect modification analyses were summarized, and matched protocol-report pairs were compared for concordance in prespecification of effect modification analyses. Findings: Of 356 protocols, 336 (94.4%) had planned effect modification analyses (median, 6 [IQR, 4-10] per protocol). Of those, 12 (3.6%) stated an anticipated direction, 176 (52.4%) planned interaction tests, and 37 (11.0%) planned within-trial analyses. Of 265 protocols using continuous variables as effect modifiers, 15 (5.7%) planned to treat all continuous variables as continuous and 72 (27.2%) planned to categorize all variables without providing justification thresholds. Of 166 identified reports, 149 (89.8%) reported effect modification analyses (median, 7 [IQR, 3-9] per study report). Among those 149 reports, 84 (56.4%) reported prespecified effect modification analyses, 125 (83.9%) reported interaction tests, and 3 (2.0%) stated anticipated effect directions. Among 133 reports using continuous variables, 87 (65.4%) used specified thresholds without providing justification for chosen cut points. Among 166 report-protocol pairs, 32 (19.3%) showed agreement on the number and factors of effect modification analyses. Of 124 mismatched pairs, 95 (76.6%) omitted 1 or more planned effect modification analyses in reports (74 [59.7%] without explanation), and 74 (59.7%) added unplanned effect modification analyses. Among 156 comparable pairs, 15 reports (9.6%) claimed prespecification for effect modification analyses absent from protocols and 84 reports (53.8%) failed to claim prespecification for effect modification analyses prespecified in protocols. Conclusions and Relevance: In this systematic review of IPDMAs, protocols and reports often failed to prespecify anticipated effect modification directions, distinguish within-trial from between-trial analyses, and appropriately handle continuous variables. Concordance between protocols and reports was poor, with frequent omission of planned and addition of unplanned effect modification analyses.
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