Evidence mapPaperPMID 41905260Full record

ArticleEBioMedicine2026

Large language models for risk-of-bias assessment in randomised clinical trials-a comparative validation study.

Lauri Nyrhi, Ville Ponkilainen, Juho Laaksonen, Lauri Kuikka, Lauri Paljakka, Teemu Karjalainen, Ville M Mattila, Ilari Kuitunen

Abstract readValidation StudyComparative Study
In one paragraph

Article in EBioMedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
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4 · The record

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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

8 authors.

Lauri NyrhiDepartment of Orthopaedics and Traumatology, Tampere University Hospital, Finland; Faculty of Medicine and Health Technology, Tampere University, Finland. Electronic address: lauri.nyrhi@tuni.fi.
Ville PonkilainenDepartment of Orthopaedics and Traumatology, Tampere University Hospital, Finland; Faculty of Medicine and Health Technology, Tampere University, Finland.
Juho LaaksonenFaculty of Medicine and Health Technology, Tampere University, Finland; Department of Surgery, Central Finland Hospital Nova, Jyväskylä, Finland.
Lauri KuikkaDepartment of Orthopaedics and Traumatology, Tampere University Hospital, Finland.
Lauri PaljakkaFaculty of Medicine and Health Technology, Tampere University, Finland.
Teemu KarjalainenFaculty of Medicine and Health Technology, Tampere University, Finland; Department of Hand- and Microsurgery, Tampere University Hospital, Finland.
Ville M MattilaDepartment of Orthopaedics and Traumatology, Tampere University Hospital, Finland; Faculty of Medicine and Health Technology, Tampere University, Finland.
Ilari KuitunenInstitute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland; Department of Pediatrics, Kuopio University Hospital, Kuopio, Finland.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundLarge language models (LLMs) are emerging tools for evidence synthesis. Risk of bias (RoB) assessment of trials remains an essential but time-consuming step inconsistent even amongst experts. Early LLM studies showed mixed reliability. Advances in reasoning-enabled models warrant evaluation of their accuracy and consistency for RoB screening across randomised trials to reduce reviewer workload.

methodsWe conducted a preregistered comparative validation study (March 11-May 19, 2025) of four LLMs-ChatGPT o3, DeepSeek v3, Google Gemini Flash 2.0, and Grok 3-prompted with full-text randomised clinical trial articles and protocols. Two corpora were analysed: 100 RCTs from recent Cochrane reviews (RoB 1) and 100 RCTs from meta-analyses in high-impact journals (RoB 2). The reference standard was published human RoB judgements. The primary outcome was interobserver reliability (Cohen κ, 95% CI); secondary outcomes were intraobserver agreement and diagnostic accuracy (sensitivity, specificity, predictive values, F

findingsFor RoB 1, interobserver agreement ranged from κ 0.0.27 (95% CI 0.07-0.46) with Gemini Flash 2.0 to κ 0.39 (0.20-0.59) with DeepSeek v3. For RoB 2, agreement was lower, from κ 0.06 (-0.07 to 0.18) with ChatGPT o3 to κ 0.13 (-0.04 to 0.31) with Gemini. Diagnostic performance was limited with sensitivity ranging 0.05-0.55, specificity 0.78-0.99, PPV 0.31-0.50, and NPV 0.48-0.61 across models, with models consistently over-flagging concerns.

interpretationNone of the evaluated LLMs were sufficiently reliable for fully autonomous RoB assessment. DeepSeek v3 and ChatGPT o3 approximated human performance best on RoB 1, but RoB 2 rule-in and rule-out performance remained modest. Current use should be supervised, with possible application of LLMs for triage or as a second assessor. Major improvements in protocol retrieval, task-specific tuning, and calibrated thresholds, prospectively validated, are needed for safe stand-alone deployment.

fundingThis study received no financial support.

Indexed as

Large Language ModelsRandomized Controlled Trials as TopicBiasHumansObserver VariationReproducibility of ResultsRisk AssessmentArtificial intelligenceLarge language modelMethodologyRisk of bias

Identifiers

PMID41905260
PMCPMC13054287

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.