Intervention effect estimates in cluster randomized versus individually randomized trials: a meta-epidemiological study
Open accessAbstract
BACKGROUND: Cluster randomized trials (CRTs) and individually randomized trials (IRTs) are often pooled together in meta-analyses (MAs) of randomized trials. However, the potential systematic differences in intervention effect estimates between these two trial types has never been investigated. Therefore, we conducted a meta-epidemiological study comparing intervention effect estimates between CRTs and IRTs. METHODS: All Cochrane MAs including at least one CRT and one IRT, published between 1 January 2010 and 31 December 2014, were included. For each MA, we estimated a ratio of odds ratios (ROR) for binary outcomes or a difference of standardized differences (DSMD) for continuous outcomes, where less than 1 (or 0, respectively) indicated a greater intervention effect estimate with CRTs. RESULTS: Among 1301 screened reviews, we selected 121 MAs, of which 76 had a binary outcome and 45 had a continuous outcome. For binary outcomes, intervention effect estimates did not differ between CRTs and IRTs [ROR 1.00, 95% confidence interval (0.93 to 1.08)]. Subgroup and adjusted analyses led to consistent results. For continuous outcomes, the DSMD was 0.13 (0.06 to 0.19). It was lower for MAs with a pharmacological intervention [-0.03, (-0.12 to 0.07)], an objective outcome [0.05, (-0.08 to 0.17)] or after adjusting for trial size [0.06, (-0.01 to 0.15)]. CONCLUSION: For binary outcomes, CRTs and IRTs can safely be pooled in MAs because of an absence of systematic differences between effect estimates. For continuous outcomes, the results were less clear although accounting for trial sample sizes led to a non-significant difference. More research is needed for continuous outcomes and, meanwhile, MAs should be completed with subgroup analyses (CRTs vs IRTs).
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Risks of bias in cluster-randomized trials often challenge the strength of the evidence generated from this design and downgrade the quality of evidence that they contribute to systematic reviews.
“These risks of bias often challenge the strength of the evidence generated from this design and downgrade the quality of evidence that they contribute to systematic reviews [22].”
From Cluster randomized trials of individual-level interventions were at high risk of bias (2021) · cites this paper as [22]
The Introduction (page unavailable) says cluster-randomized trials are more susceptible to bias than individually randomized trials and describes recruitment bias, supporting the concern about the strength of their evidence. The paper does not say that these risks often downgrade the quality of evidence in systematic reviews; its Conclusion (page unavailable) says the two trial types can safely be pooled for binary outcomes. (LLM, conf=0.86)
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- Authors
- Leyrat, C., Caille, A., Eldridge, S., Kerry, S., Dechartres, A., & Giraudeau, B.
- Affiliations
- London School of Hygiene & Tropical Medicine (GB)
- Université de Tours (FR)
- Queen Mary University of London (GB)
- Inserm (FR)
- Corresponding author
- Leyrat, Clémence
- Venue
- International Journal of Epidemiology
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-11-09
- Volume
- 48
- Issue
- 2
- Pages
- 609-619
- ISSN
- 0300-5771 (ISSN-L)
- 1464-3685
- PMC
- PMC6469309
- OpenAlex
- W2899970630
- Cited by
- 20
- References
- 32
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 6 · 2021: 4 · 2020: 1 · 2019: 4
- FWCI
- 0.44
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- International Journal of Epidemiology (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- HAL (submittedVersion, other-oa)
- Funders
- French Ministry of Health (PREPS 13-0015)
- Topics
- Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Social Sciences › Sociology and Political Science › Delphi Technique in Research
- Keywords
- meta-epidemiology, standardized mean difference, binary outcomes, continuous outcomes, subgroup analysis, pharmacological interventions, objective outcomes
- MeSH terms
- Systematic Reviews as Topic, Data Collection, Humans, Meta-Analysis as Topic, Epidemiologic Studies, Randomized Controlled Trials as Topic, Sample Size
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