Evidence mapPaperPMID 40175893Full record

ReviewBMC medical research methodology2025

Combining treatment effects from mixed populations in meta-analysis: a review of methods.

Lorna Wheaton, Sandro Gsteiger, Stephanie Hubbard, Sylwia Bujkiewicz

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In one paragraph

Review in BMC medical research methodology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Lorna WheatonBiostatistics Research Group, Department of Population Health Sciences, University of Leicester, University Road, Leicester, LE1 7RH, UK. lskw3@leicester.ac.uk.
Sandro GsteigerGlobal Access, F Hoffman-La Roche AG, Basel, Switzerland.
Stephanie HubbardBiostatistics Research Group, Department of Population Health Sciences, University of Leicester, University Road, Leicester, LE1 7RH, UK.
Sylwia BujkiewiczBiostatistics Research Group, Department of Population Health Sciences, University of Leicester, University Road, Leicester, LE1 7RH, UK.

Funding

Medical Research Council MR/T025166/1Wellcome Trust
6 · The paper itself

Abstract

backgroundMeta-analysis is a useful method for combining evidence from multiple studies to detect treatment effects that could perhaps not be identified in a single study. While traditionally meta-analysis has assumed that populations of included studies are comparable, over recent years the development of precision medicine has led to identification of predictive genetic biomarkers which has resulted in trials conducted in mixed biomarker populations. For example, early trials may be conducted in patients with any biomarker status with no subgroup analysis, later trials may be conducted in patients with any biomarker status and subgroup analysis, and most recent trials may be conducted in biomarker-positive patients only. This poses a problem for traditional meta-analysis methods which rely on the assumption of somewhat comparable populations across studies. In this review, we provide a background to meta-analysis methods allowing for synthesis of data with mixed biomarker populations across trials.

methodsFor the methodological review, PubMed was searched to identify methodological papers on evidence synthesis for mixed populations. Several identified methods were applied to an illustrative example in metastatic colorectal cancer.

resultsWe identified eight methods for evidence synthesis of mixed populations where three methods are applicable to pairwise meta-analysis using aggregate data (AD), three methods are applicable to network meta-analysis using AD, and two methods are applicable to network meta-analysis using AD and individual participant data (IPD). The identified methods are described, including a discussion of the benefits and limitations of each method.

conclusionsMethods for synthesis of data from mixed populations are split into methods which use (a) AD, (b) IPD, and (c) both AD and IPD. While methods which utilise IPD achieve superior statistical qualities, this is at the expense of ease of access to the data. Furthermore, it is important to consider the context of the decision problem in order to select the most appropriate modelling framework.

Indexed as

Meta-Analysis as TopicPrecision MedicineBiomarkersColorectal NeoplasmsHumansResearch DesignTreatment OutcomeBiomarkersBiomarkerMeta-analysisSubgroup

Identifiers

PMID40175893
PMCPMC11963434

What Socratic holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.