International Journal of Epidemiology 2002;31:140-149
© International Epidemiological Association 2002
Special Theme: Systematic Reviews and Meta-Analysis |
Meta-analyses involving cross-over trials: methodological issues
a Medical Statistics Unit, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
b ICRF Medical Statistics Group, Centre for Statistics in Medicine, Institute of Health Sciences, Old Road, Headington, Oxford OX3 7LF, UK.
c MRC Biostatistics Unit, Institute of Public Health, Robinson Way, Cambridge CB2 2SR, UK.
d Oral Health and Development, University Dental Hospital of Manchester, Higher Cambridge Street, Manchester M15 6FH, UK.
e R & D Academic Affairs Directorate, Clinical Sciences Building, Hope Hospital, Stott Lane, Salford M6 8HD, UK.
Prof. Diana Elbourne, Medical Statistics Unit, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK. E-mail: diana.elbourne{at}lshtm.ac.uk
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.
Keywords Cross-over trials, meta-analysis
Accepted 18 October 2001
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