Combining effect sizes from controlled and uncontrolled study designs: benefit, bias, and control strategies

Article type
Authors
Nestoriuc Y, Martin A, Rief W
Abstract
Background: Most meta-analyses focus on the integration of evidence from randomized controlled trials (RCTs). The exclusion of quasi-experimental designs (e.g., uncontrolled before-and-after studies) can lead to a significant loss of information, decreased power for moderator analyses, and reduced generalizability of the results. Objectives: To consider methods and related evidence for integrating effects sizes from different study designs and to identify potential biases. Methods: Two metaanalyses from the field of behavioral headache therapy were re-analysed to exemplify the impact of integrating effect sizes from controlled and uncontrolled study designs. Sensitivity analyses were carried out with respect to type of study design, study quality, and varying formulas for effect size computation. Results: In behavioural headache research (i.e., biofeedback for migraine and tensions-type headache), 40% of the treatment studies have been conducted without control groups. Mean effect size estimates from uncontrolled studies and RCTs did not differ significantly with respect to size, while heterogeneity was greater within the uncontrolled trials. Study quality as assessed with a structured validity rating was uncorrelated with effect sizes. Mean effect sizes from untreated control groups provided some further evidence for the validity of uncontrolled trials, ruling out possible confounding effects such as cohort, seasonality and regression to the mean. Conclusions: The integration of RCTs as well as uncontrolled trials has lead to more generalizable results in the case of the two reanalysed meta-analysis, though at the cost of increased heterogeneity of results. Since no systematic over- or underestimation of the mean effect was observed and potential confounds of effects were controlled for and proved unlikely in the field of behavioral headache research, the results are considered reliable. However, the validity of uncontrolled studies has to be evaluated with respect to each particular area of research.