Cited by 2,305Meta-analysis and systematic reviewsStatistical Methods in Clinical TrialsStatistical Methods in Epidemiology

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Meta-analyses involving cross-over trials: methodological issues

Elbourne, Diana R, Altman, Douglas G, Higgins, Julian PT, Curtin, Francois, Worthington, Helen V, Vail, Andy·2002·International Journal of Epidemiology

DOI 10.1093/ije/31.1.140

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Abstract

BACKGROUND: Meta-analysis of randomized controlled trials (RCTs) is usually based on trials where patients are randomized individually into two different, parallel, treatment groups. This paper concentrates on RCTs of a different design-two-period, two-treatment cross-over trials. METHODS: The characteristics of these trials are outlined, with detailed examples of methods for analysis for both continuous and binary data. These case studies are then extended into the context of a meta-analysis. The Cochrane Library was surveyed to assess current practice for synthesis. RESULTS: Methods are described for continuous and binary data for use both when the necessary paired data are given and also when they need to be calculated or imputed, and some suggestions are provided to help people wishing to synthesize data from cross-over trials into meta-analyses. The survey suggested that about 8% of the trials in the Cochrane library were cross-over trials and 18% of the reviews referred to such trials, although there was no consistent approach to their inclusion into the reviews. CONCLUSIONS: Methods do exist for including valuable information from two-period, two-treatment cross-over trials into quantitative reviews. However, poor reporting of cross-over trials will often impede attempts to perform a meta-analysis using the available methods.

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Guided tissue regeneration for periodontal infra-bony defects
Needleman, I. G., Worthington, H. V., Giedrys‐Leeper, E., & Tucker, R. (2006) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd001724.pub2 · Cited by 372
Self-citation
Retracted
Opioids for the palliation of breathlessness in advanced disease and terminal illness.
Jennings, A. L., Davies, A. N., Higgins, J. P. T., Anzures‐Cabrera, J., & Broadley, K. E. (2001) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd002066 · Cited by 190
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Dehydroepiandrosterone (DHEA) supplementation for cognitive function.
Huppert, F., & Van Niekerk, J. (2001) · The Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd000304 · Cited by 88
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Book Reviews: Statistical Methods for Meta-Analysis Larry V. Hedges and Ingram Olkin New York: Academic Press, 1985. xxii + 369 pp
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Systematic Reviews in Health Care : Meta-Analysis in Context
Egger, M., Smith, G. D., & Altman, D. G. (2000) · Cited by 2,312
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Statistical Methods for Examining Heterogeneity and Combining Results from Several Studies in Meta‐Analysis
Deeks, J. J., Altman, D. G., & Bradburn, M. J. (2001) · Systematic Reviews in Health Care · doi:10.1002/9780470693926.ch15 · Cited by 2,163
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Retracted
Appetite stimulants for people with cystic fibrosis
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Authors: Elbourne, D. R., Altman, D. G., Higgins, J. P., Curtin, F., Worthington, H. V., & Vail, A.
Affiliations: London School of Hygiene & Tropical Medicine (GB)
Merck KGaA, Darmstadt (Germany) (DE)
University Dental Hospital of Manchester (GB)
Salford Royal Hospital (GB)
Corresponding author: Elbourne, Diana R
ORCID: Altman, Douglas G
Higgins, Julian PT
Worthington, Helen V
Vail, Andy
Venue: International Journal of Epidemiology
Publisher: Oxford University Press (OUP)
Published: 2002-02
Volume: 31
Issue: 1
Pages: 140-149
ISSN: 0300-5771 (ISSN-L)
1464-3685
DOI: 10.1093/ije/31.1.140
OpenAlex: W2130235475
Cited by: 2,305
References: 37
Citations by year: 2026: 58 · 2025: 58 · 2024: 72 · 2023: 87 · 2022: 116 · 2021: 129 · 2020: 107 · 2019: 111 · 2018: 128 · 2017: 131 · 2016: 145 · 2015: 147 · 2014: 174 · 2013: 135 · 2012: 144
FWCI: 47.29
Type: journal article
Language: en
Open access: closed
Locations: International Journal of Epidemiology (publishedVersion)
PubMed (publishedVersion)
Research Explorer (The University of Manchester) (submittedVersion)
Funders: Medical Research Council
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
Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Epidemiology
Keywords: crossover trial, meta-analysis, randomized controlled trials, continuous data, binary data, missing data imputation, trial reporting quality, Cochrane Library
MeSH terms: Humans, Review Literature as Topic, Meta-Analysis as Topic, Randomized Controlled Trials as Topic, Cross-Over Studies

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