Concordance between target trial emulation and randomised controlled trials: systematic review and meta-analysis
- 1School of Life Course and Population Sciences, King's College London, London, UK
- 2Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, BC, Canada
- 3Research Department of Practice and Policy, School of Pharmacy, University College London, London, UK
Abstract
Objectives To assess the concordance of results between paired target trial emulations and their benchmarking randomised controlled trials and to explore determinants of emulation success. Design Systematic review and meta-analysis. Data sources Medline, EMBASE, Scopus, PsycINFO, and Web of Science (2010 to 2025). Study selection Observational studies that explicitly aimed to emulate target randomised controlled trials of a health intervention were included. Data extraction Data were extracted on study domain, target population, intervention, comparator, and main outcomes for each emulation and corresponding randomised controlled trial. Main outcome measures For 21 predefined emulation design features, concordance was assessed using Pearson correlation coefficients, standardised difference agreement, and ratio of ratios, with subgroup and regression analyses of study characteristics and concordance. Results Among 106 target trial emulation-randomised controlled trial pairs, the Pearson correlation coefficient was 0.58 (95% confidence interval (CI) 0.43 to 0.69), standardised difference agreement was 79% (84/106), and summary ratio of ratios was 0.97 (95% CI 0.92 to 1.03; I 2 =42%). In 62 pairs with closer emulation of trial design, a higher level of agreement was observed, with a Pearson correlation coefficient of 0.83 (0.73 to 0.89) and standardised difference agreement of 87% (54/62). In subgroup analysis, trial emulations tended to systematically underestimate treatment effects from randomised controlled trials for specific outcomes related to venous thromboembolism and major adverse cardiovascular events, while overestimating those for respiratory outcomes, with pooled ratio of ratios of 0.76 (0.58 to 1.00; I 2 =40%), 0.91 (0.85 to 0.98; I 2 =35%), and 1.20 (1.03 to 1.40; I 2 =40%), respectively. Moreover, emulations based on claims data tended to underestimate the treatment effects (ratio of ratios 0.89, 0.81 to 0.98; I 2 =39%). In exploratory univariate regression analyses, poorer target trial emulation-randomised controlled trial concordance was associated with emulation designs with imbalanced baseline population characteristics, delayed treatment effect, and lower outcome emulation quality. Conclusions Current target trial emulations achieve moderate concordance when replicating their corresponding randomised controlled trials. Concordance could be improved by better emulation design, including better baseline and outcome emulation and leveraging multisource linked databases. Systematic review registration PROSPERO CRD42024619811.
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BibTeX
@article{wang2026concordance,
title = {{Concordance between target trial emulation and randomised controlled trials: systematic review and meta-analysis}},
author = {C H Wang and Dongfeng Tang and Peter von Dadelszen and Chengsheng Ju and Lu Liu and Yanzhong Wang and Laura Ann Magee},
journal = {BMJ},
year = {2026},
month = may,
doi = {10.1136/bmj-2025-086810},
url = {https://doi.org/10.1136/bmj-2025-086810},
note = {CC BY},
}
RIS
TY - JOUR
TI - Concordance between target trial emulation and randomised controlled trials: systematic review and meta-analysis
AU - C H Wang
AU - Dongfeng Tang
AU - Peter von Dadelszen
AU - Chengsheng Ju
AU - Lu Liu
AU - Yanzhong Wang
AU - Laura Ann Magee
PY - 2026
DA - 2026/05/19
JO - BMJ
DO - 10.1136/bmj-2025-086810
UR - https://doi.org/10.1136/bmj-2025-086810
AB - Objectives To assess the concordance of results between paired target trial emulations and their benchmarking randomised controlled trials and to explore determinants of emulation success. Design Systematic review and meta-analysis. Data sources Medline, EMBASE, Scopus, PsycINFO, and Web of Science (2010 to 2025). Study selection Observational studies that explicitly aimed to emulate target randomised controlled trials of a health intervention were included. Data extraction Data were extracted on study domain, target population, intervention, comparator, and main outcomes for each emulation and corresponding randomised controlled trial. Main outcome measures For 21 predefined emulation design features, concordance was assessed using Pearson correlation coefficients, standardised difference agreement, and ratio of ratios, with subgroup and regression analyses of study characteristics and concordance. Results Among 106 target trial emulation-randomised controlled trial pairs, the Pearson correlation coefficient was 0.58 (95% confidence interval (CI) 0.43 to 0.69), standardised difference agreement was 79% (84/106), and summary ratio of ratios was 0.97 (95% CI 0.92 to 1.03; I 2 =42%). In 62 pairs with closer emulation of trial design, a higher level of agreement was observed, with a Pearson correlation coefficient of 0.83 (0.73 to 0.89) and standardised difference agreement of 87% (54/62). In subgroup analysis, trial emulations tended to systematically underestimate treatment effects from randomised controlled trials for specific outcomes related to venous thromboembolism and major adverse cardiovascular events, while overestimating those for respiratory outcomes, with pooled ratio of ratios of 0.76 (0.58 to 1.00; I 2 =40%), 0.91 (0.85 to 0.98; I 2 =35%), and 1.20 (1.03 to 1.40; I 2 =40%), respectively. Moreover, emulations based on claims data tended to underestimate the treatment effects (ratio of ratios 0.89, 0.81 to 0.98; I 2 =39%). In exploratory univariate regression analyses, poorer target trial emulation-randomised controlled trial concordance was associated with emulation designs with imbalanced baseline population characteristics, delayed treatment effect, and lower outcome emulation quality. Conclusions Current target trial emulations achieve moderate concordance when replicating their corresponding randomised controlled trials. Concordance could be improved by better emulation design, including better baseline and outcome emulation and leveraging multisource linked databases. Systematic review registration PROSPERO CRD42024619811.
SN - 1756-1833
ER -