Riberholt, Christian Gunge and Olsen, Markus Harboe and Milan, Joachim Birch and Haflioadottir, Sigurlaug Hanna and Svanholm, Jeppe Houmann and Pedersen, Elisabeth Buck and Lew, Charles Chin Han and Asante, Mark Aninakwah and Ribeiro, Johanne Pereira and Wagner, Vibeke and Kumburegama, Buddheera W. M. B. and Lee, Zheng-Yii and Schaug, Julie Perrine and Madsen, Christina and Gluud, Christian (2024) Major mistakes or errors in the use of trial sequential analysis in systematic reviews or meta-analyses - the METSA systematic review. BMC Medical Research Methodology, 24 (1). ISSN 1471-2288, DOI https://doi.org/10.1186/s12874-024-02318-y.
Full text not available from this repository.Abstract
Background Systematic reviews and data synthesis of randomised clinical trials play a crucial role in clinical practice, research, and health policy. Trial sequential analysis can be used in systematic reviews to control type I and type II errors, but methodological errors including lack of protocols and transparency are cause for concern. We assessed the reporting of trial sequential analysis. Methods We searched Medline and the Cochrane Database of Systematic Reviews from 1 January 2018 to 31 December 2021 for systematic reviews and meta-analysis reports that include a trial sequential analysis. Only studies with at least two randomised clinical trials analysed in a forest plot and a trial sequential analysis were included. Two independent investigators assessed the studies. We evaluated protocolisation, reporting, and interpretation of the analyses, including their effect on any GRADE evaluation of imprecision. Results We included 270 systematic reviews and 274 meta-analysis reports and extracted data from 624 trial sequential analyses. Only 134/270 (50%) systematic reviews planned the trial sequential analysis in the protocol. For analyses on dichotomous outcomes, the proportion of events in the control group was missing in 181/439 (41%), relative risk reduction in 105/439 (24%), alpha in 30/439 (7%), beta in 128/439 (29%), and heterogeneity in 232/439 (53%). For analyses on continuous outcomes, the minimally relevant difference was missing in 125/185 (68%), variance (or standard deviation) in 144/185 (78%), alpha in 23/185 (12%), beta in 63/185 (34%), and heterogeneity in 105/185 (57%). Graphical illustration of the trial sequential analysis was present in 93% of the analyses, however, the Z-curve was wrongly displayed in 135/624 (22%) and 227/624 (36%) did not include futility boundaries. The overall transparency of all 624 analyses was very poor in 236 (38%) and poor in 173 (28%). Conclusions The majority of trial sequential analyses are not transparent when preparing or presenting the required parameters, partly due to missing or poorly conducted protocols. This hampers interpretation, reproducibility, and validity.
| Item Type: | Article |
|---|---|
| Funders: | Copenhagen University |
| Uncontrolled Keywords: | Meta-analysis; Methodology; Research-on-research; Systematic review; Trial sequential analysis |
| Subjects: | R Medicine > RA Public aspects of medicine |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 13 Oct 2025 13:22 |
| Last Modified: | 13 Oct 2025 13:22 |
| URI: | http://eprints.um.edu.my/id/eprint/46504 |
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