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Major mistakes or errors in the use of trial sequential analysis in systematic reviews or meta-analyses – the METSA systematic review

the METSA systematic review
Authors: Christian Gunge Riberholt; Markus Harboe Olsen; Joachim Birch Milan; Sigurlaug Hanna Hafliðadóttir; Jeppe Houmann Svanholm; Elisabeth Buck Pedersen; Charles Chin Han Lew; +8 Authors

Major mistakes or errors in the use of trial sequential analysis in systematic reviews or meta-analyses – the METSA systematic review

Abstract

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. Study registration PROSPERO CRD42021273811

Keywords

Research-on-research, Trial sequential analysis, Medicine (General), Research, Methodology, Meta-analysis, Research Design/standards [MeSH] ; Trial sequential analysis ; Randomized Controlled Trials as Topic/standards [MeSH] ; Humans [MeSH] ; Systematic review ; Meta-analysis ; Randomized Controlled Trials as Topic/methods [MeSH] ; Research-on-research ; Methodology ; Research ; Randomized Controlled Trials as Topic/statistics ; Meta-Analysis as Topic [MeSH] ; Systematic Reviews as Topic/methods [MeSH], R5-920, Randomized Controlled Trials as Topic/methods, Meta-Analysis as Topic, Research Design, Systematic review, Humans, Systematic Reviews as Topic/methods, Research Design/standards, Systematic Reviews as Topic, Randomized Controlled Trials as Topic

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    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
6
Top 10%
Average
Top 10%
Green
gold