Abstract
Objectives
A survey of randomized controlled trials found that almost a quarter of trials had
more than 10% of responses missing for the primary outcome. There are a number of
ways in which data could be missing: the subject is unable to provide it, or they
withdraw, or become lost to follow-up. Such attrition means that balance in baseline
characteristics for those randomized may not be maintained in the subsample who has
outcome data. For individual trials, if the attrition is systematic and linked to
outcome, then this will result in biased estimates of the overall effect. It then
follows that if such trials are combined in a meta-analysis, it will result in a biased
estimate of the overall effect and be misleading. The aim of this study was to investigate
the impact of attrition on baseline imbalance within individual trials and across
multiple trials.
Study Design and Setting
In this article, we used individual patient data from a convenience sample of 10 trials
evaluating interventions for the treatment of musculoskeletal disorders. Meta-analyses
using the mean difference at baseline between the trial arms were carried out using
individual patient data from these trials. The analyses were first carried out using
all randomized participants and secondly only including participants with outcome
data on the quality-of-life score. Meta-regression was carried out to evaluate whether
the level of baseline imbalance was associated with the level of attrition.
Results
The overall attrition rates for the quality-of-life score ranged between 4% and 28%
of the total randomized patients. All trials showed some level of differential attrition
between the treatment arms, ranging from 1% to 14%. Attrition within the control group
ranged from 3% to 25% and within the intervention group, it ranged from 0% to 31%.
For individual trials, there was no indication that attrition altered the results
in favor of either the treatment or the control. Forest plots highlighted that the
attrition had some impact on the baseline imbalance for the primary outcome score
as more heterogeneity was introduced (I-squared value of 0.4% for the initial data
set vs. I-squared value of 16.9% for the analyzed data set). However, the standardized
mean difference increased only slightly (from 0.01 to 0.03 with 95% confidence interval
[CI]: −0.05, 0.10). Meta-regression showed little or no evidence of a significant
dose–response relationship between the level of attrition and the baseline imbalance
(coefficient 0.73, 95% CI: −0.81, 2.28).
Conclusion
Although, in theory, attrition can introduce selection bias in randomized trials,
we did not find sufficient evidence to support this claim in our convenience sample
of trials. However, the number of trials included was relatively small, which may
have led to small but important differences in outcomes being missed. In addition,
only 2 of 10 trials included had attrition levels greater than 15% suggesting a low
level of potential bias. Meta-analyses and systematic reviews should always consider
the impact of attrition on baseline imbalances and where possible any baseline imbalances
in the analyzed data set and their impact on the outcomes reported.
Keywords
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Article info
Publication history
Published online: June 23, 2010
Accepted:
January 22,
2010
Footnotes
This article was a joint collaboration with the members of the trial attrition study group: Stephen D. Brealey, Jo C. Dumville, Elaine M. Hay, Catherine E. Hewitt, Jennifer A. Klaber Moffett, Bharathy Kumaravel, Hugh MacPherson, Elaine Thomas, David J. Torgerson, and Jude Watson.
Contributors: J.C.D. had the idea of studying the impact of attrition in a sample of randomized controlled trials (RCTs). B.K. carried out the analysis under the guidance of C.E.H., D.J.T., and J.C.D. D.J.T. is the director of the York Trials Unit and identified trials for this study. The study used a convenience sample of 10 RCTs of musculoskeletal trials for which we obtained permission to use the individual patient data. E.M.H., J.A.K.M., H.MacP., S.D.B., J.W., and D.J.T. contributed data to the study. The authors wrote the article and the trial attrition study group critically reviewed versions of the manuscript. C.E.H. is the guarantor.
Funding: No additional funding.
Competing interests: None declared.
Provenance and peer review: Not commissioned; peer reviewed by the trial attrition study group.
Identification
Copyright
© 2010 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
