Evidence mapPaperPMID 41793162Full record

SynthesisReviews in medical virology2026

The Impact of Study Size on COVID-19 Treatment Outcomes: A Meta-Epidemiological Study Comparing Large and Small Randomized Controlled Trials: A Systematic Review and Meta-Analyses.

Dong Hyun Kim, Soojin Lim, Michael Eisenhut, Andreas Kronbichler, Eunyoung Kim, Min Seo Kim, Stefania I Papatheodorou, Justin Stebbing, Yonghong Peng, Sarah Soyeon Oh and 2 more

Abstract readSystematic ReviewMeta-Analysis
In one paragraph

Synthesis in Reviews in medical virology, 2026. 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

12 authors.

Dong Hyun KimYonsei University College of Medicine, Seoul, Korea.ORCID 0009-0002-5618-1472
Soojin LimYonsei University College of Medicine, Seoul, Korea.
Michael EisenhutLuton & Dunstable University Hospital, Bedfordshire Hospitals NHS Foundation Trust, Luton, UK.ORCID 0000-0002-8505-1186
Andreas KronbichlerDepartment of Internal Medicine IV, Nephrology and Hypertension, Medical University Innsbruck, Innsbruck, Austria.
Eunyoung KimData Science, Evidence-Based and Clinical Research Laboratory, Department of Health, Social and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, Seoul, Korea.ORCID 0000-0003-3525-8805
Min Seo KimCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Stefania I PapatheodorouDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
Justin StebbingSchool of Life Sciences, Anglia Ruskin University, Cambridge, UK.ORCID 0000-0002-1117-6947
Yonghong PengFaculty of Science and Engineering, Anglia Ruskin University, Cambridge, UK.ORCID 0000-0002-5508-1819
Sarah Soyeon OhInstitute for Global Engagement & Empowerment, Yonsei University, Seoul, Korea.
Jae Il ShinDepartment of Pediatrics, Yonsei University College of Medicine, Seoul, Korea.ORCID 0000-0003-2326-1820
Lee SmithCentre for Health, Performance and Wellbeing, Anglia Ruskin University, Cambridge, UK.

Funding

Yonsei Fellowship
6 · The paper itself

Abstract

Small randomized controlled trials (RCTs) in COVID-19 meta-analyses have been associated with more favourable treatment effects and reduced result stability. This study assessed how trial size impacts effect estimates, statistical stability, and risk of bias. Following PRISMA guidelines, we identified meta-analyses of COVID-19 treatments included in WHO, NIH, and the LIVING Project. Trials were classified by log-scale sample size, and separate pooled meta-analyses were conducted for large-only, small-only, and combined trials. Comparative metrics included the Ratio of Odds Ratios (ROR), Kappa statistics, Fragility Index (FI), Reverse Fragility Index (RFI), and Cochrane Risk of Bias assessments. Sensitivity analyses applied alternative size thresholds (≥ 1000 participants and median-based cutoffs) and stratified results by treatment and outcome type. Across 25 meta-analyses including 221 RCTs (46 large, 175 small), small trials produced more extreme estimates in 19 analyses and wider confidence intervals in 23. The pooled ROR was 0.85 (95% CI: 0.76-0.95; P = 0.004), decreasing to 0.81 (95% CI: 0.68-0.95; P = 0.011) when limited to small trials published before the first large trial. RORs remained below 1 across treatment and outcome types. Agreement between small and large trials was minimal, while large trials showed substantial agreement with overall estimates. Stability and bias profiles favoured large trials (FI: 14.0 vs. 4.0; RFI: 10.0 vs. 5.0). In conclusion, small RCTs tend to overestimate treatment effects and yield less precise, less stable results. Meta-analyses should prioritise large, high-quality trials and interpret small-study findings with caution, particularly in rapidly evolving research contexts.

Indexed as

Antiviral AgentsCOVID-19COVID-19 Drug TreatmentRandomized Controlled Trials as TopicHumansSample SizeSARS-CoV-2Treatment OutcomeAntiviral AgentsbiasCOVID‐19meta‐epidemiologyrandomized controlled trialssmall‐study effectstreatment outcome

Identifiers

PMID41793162
PMCPMC12966952

What Socratic holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.