Design, Analysis, and Reporting of Crossover Trials for Inclusion in a Meta-Analysis
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OBJECTIVE: To evaluate the characteristics of the design, analysis, and reporting of crossover trials for inclusion in a meta-analysis of treatment for primary open-angle glaucoma and to provide empirical evidence to inform the development of tools to assess the validity of the results from crossover trials and reporting guidelines. METHODS: We searched MEDLINE, EMBASE, and Cochrane's CENTRAL register for randomized crossover trials for a systematic review and network meta-analysis we are conducting. Two individuals independently screened the search results for eligibility and abstracted data from each included report. RESULTS: We identified 83 crossover trials eligible for inclusion. Issues affecting the risk of bias in crossover trials, such as carryover, period effects and missing data, were often ignored. Some trials failed to accommodate the within-individual differences in the analysis. For a large proportion of the trials, the authors tabulated the results as if they arose from a parallel design. Precision estimates properly accounting for the paired nature of the design were often unavailable from the study reports; consequently, to include trial findings in a meta-analysis would require further manipulation and assumptions. CONCLUSIONS: The high proportion of poorly reported analyses and results has the potential to affect whether crossover data should or can be included in a meta-analysis. There is pressing need for reporting guidelines for crossover trials.
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Non-daily vs. daily statin dosing resulted in an odds ratio of 0.58 (95% CI 0.23-1.43) for incidence of muscle symptoms.
“Non-daily vs. daily statin dosing resulted in an OR of 0.58 (95% CI 0.23–1.43). [34,51,52].”
From Safety outcomes of statin vs non-statin lipid-lowering interventions in patients with prior statin-associated muscle symptoms: A systematic review and meta-analysis (2025) · cites this paper as [51]
The Results sections on reporting and meta-analysis inclusion discuss estimates from crossover trials, not statin dosing or muscle symptoms (page numbers unavailable). Searches for the stated odds ratio and for statin muscle symptoms found no passage supporting the claimed result. (LLM, conf=0.78)
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Cites
Meta-analyses involving cross-over trials: methodological issues
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CONSORT 2010 statement: extension to randomised crossover trials
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“[34,51,52].”
- Authors
- Li, T., Yu, T., Hawkins, B. S., & Dickersin, K.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Li, Tianjing
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2015-08-18
- Volume
- 10
- Issue
- 8
- Pages
- e0133023
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4540315
- OpenAlex
- W1850821928
- Cited by
- 107
- References
- 1
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 8 · 2023: 11 · 2022: 10 · 2021: 17 · 2020: 15 · 2019: 18 · 2018: 8 · 2017: 3 · 2016: 2 · 2015: 1
- FWCI
- 4.26
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- National Eye Institute (U01EY020522, RC1EY020140)
- 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
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Keywords
- crossover trial, primary open-angle glaucoma, network meta-analysis, trial reporting quality, reporting guidelines, residual effects, period effects, missing data, within-person variability, risk of bias
- MeSH terms
- Glaucoma, Open-Angle, Humans, Research Design, Meta-Analysis as Topic, Randomized Controlled Trials as Topic, Cross-Over Studies
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