Colwill M, Hall R, Ezekwe S, Pollok R, Poullis A. Problems of meta-analysis to explore rare diseases. World J Meta-Anal 2025; 13(4): 111946 [DOI: 10.13105/wjma.v13.i4.111946]
Corresponding Author of This Article
Michael Colwill, MRCP, Research Fellow, Department of Gastroenterology, St George's University Hospitals NHS Foundation Trust, Blackshaw Road, London SW17 0QT, United Kingdom. michael.colwill@nhs.net
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Methodology
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Minireviews
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Dec 18, 2025 (publication date) through Jan 8, 2026
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Publication Name
World Journal of Meta-Analysis
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2308-3840
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Colwill M, Hall R, Ezekwe S, Pollok R, Poullis A. Problems of meta-analysis to explore rare diseases. World J Meta-Anal 2025; 13(4): 111946 [DOI: 10.13105/wjma.v13.i4.111946]
World J Meta-Anal. Dec 18, 2025; 13(4): 111946 Published online Dec 18, 2025. doi: 10.13105/wjma.v13.i4.111946
Problems of meta-analysis to explore rare diseases
Michael Colwill, Richard Hall, Stephanie Ezekwe, Richard Pollok, Andrew Poullis
Michael Colwill, Richard Hall, Stephanie Ezekwe, Richard Pollok, Department of Gastroenterology, St George's University Hospitals NHS Foundation Trust, London SW17 0QT, United Kingdom
Michael Colwill, Richard Pollok, Andrew Poullis, Institute of Infection and Immunity, City St George's, University of London, London SW17 0RE, United Kingdom
Andrew Poullis, Department of Gastroenterology, St George's Hospital, London SW17 0QT, United Kingdom
Author contributions: Colwill M contributed to investigation and writing - original draft; Poullis A contributed to supervision; Colwill M, Hall R, Ezekwe S, Pollok R, and Poullis A contributed to writing - review and editing.
Conflict-of-interest statement: Colwill M served as a speaker and an advisory board member of or has received grants from Pfizer, Celltrion, Ferring, and Dr. Falk.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Michael Colwill, MRCP, Research Fellow, Department of Gastroenterology, St George's University Hospitals NHS Foundation Trust, Blackshaw Road, London SW17 0QT, United Kingdom. michael.colwill@nhs.net
Received: July 14, 2025 Revised: August 11, 2025 Accepted: November 4, 2025 Published online: December 18, 2025 Processing time: 157 Days and 15.2 Hours
Core Tip
Core Tip: Meta-analysis is essential in evidence-based medicine but presents challenges in rare diseases due to limited studies, small sample sizes, and reliance on observational data. These factors reduce statistical power, increase bias, and limit generalizability. Heterogeneity in patient characteristics and study design further complicates analysis, while traditional statistical methods may yield unreliable estimates. Collaborative networks, disease registries, and advanced techniques like Bayesian methods or the Hartung-Knapp-Sidik-Jonkman approach can help address these limitations. In some cases, scoping reviews may be more appropriate. Recognizing and managing these challenges is crucial to improving evidence quality and clinical outcomes in rare disease research.
