Review Article

Korean J Pain 2021; 34(2): 139-155

Published online April 1, 2021 https://doi.org/10.3344/kjp.2021.34.2.139

Copyright © The Korean Pain Society.

The quality of subgroup analyses in chronic pain randomized controlled trials: a methodological review

Mahmood AminiLari1,2 , Vahid Ashoorian2 , Alexa Caldwell3 , Yasir Rahman1,2 , Robby Nieuwlaat1 , Jason W. Busse1,2,5 , Lawrence Mbuagbaw1,4

1Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
2Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, Ontario, Canada
3Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
4Biostatistics Unit, St Joseph’s Healthcare Hamilton, Hamilton, Ontario, Canada
5Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada

Correspondence to:Mahmood AminiLari
Department of Health Research Methods, Evidence and Impact (HEI), Faculty of Health Sciences, McMaster University, 1280 Main Street West, 2C Area, Hamilton, ON L8S 4K1, Canada
Tel: +1-905-554-7283
Fax: +1-905-526-1289
E-mail: aminilam@mcmaster.ca

Handling Editor: Hyun Kang

Received: September 28, 2020; Revised: November 16, 2020; Accepted: November 25, 2020

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


The quality of subgroup analyses (SGAs) in chronic non-cancer pain trials is uncertain. The purpose of this study was to address this issue. We conducted a comprehensive search in MEDLINE and EMBASE from January 2012 to September 2018 to identify eligible trials. Two pairs of reviewers assessed the quality of the SGAs and the credibility of subgroup claims using the 10 criteria developed by Sun et al. in 2012. The associations between the quality of the SGAs and the studies’ characteristics including risk of bias, funding sources, sample size, and the latest impact factor, were assessed using multivariable logistic regression. Our search retrieved 3,401 articles of which 66 were eligible. The total number of SGAs was 177 of which 52 (29.4%) made a subgroup claim. Of these, only 15 (8.5%) were evaluated as being of high quality. Among the 30 SGAs that claimed subgroup effects using an appropriate method of performing interaction tests, the credibility of only 5 were assessed as high. None of the subgroup claims met all the credibility criteria. No significant association was found between the quality of SGAs and the studies’ characteristics. The quality of the SGAs performed in chronic pain trials was poor. To enhance the quality of SGAs, scholars should consider the developed criteria when designing and conducting trials, particularly those which need to be specified a priori .

Keywords: Bias, Chronic Pain, Logistic Models, MEDLINE, Methods, Pain, Research Design, Uncertainty.