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Systematic reviews and meta-analyses of mediation studies are increasingly being implemented in practice. Nonetheless, the methodology for conducting such review and analysis is still in a development phase, with much room for improvement. In this paper, we highlight and discuss challenges that investigators face in systematic reviews and meta-analyses of mediation studies and propose ways of accommodating these in practice. [ABSTRACT FROM AUTHOR]

Case‐mix heterogeneity across studies complicates meta‐analyses. As a result of this, treatments that are equally effective on patient subgroups may appear to have different effectiveness on patient populations with different case mix. It is therefore important that meta‐analyses be explicit for what patient population they describe the treatment effect. To achieve this, we develop a new approach for meta‐analysis of randomized clinical trials, which use individual patient data (IPD) from all trials to infer the treatment effect for the patient population in a given trial, based on direct standardization using either outcome regression (OCR) or inverse probability weighting (IPW). Accompanying random‐effect meta‐analysis models are developed. The new approach enables disentangling heterogeneity due to case mix from that due to beyond case‐mix reasons. [ABSTRACT FROM AUTHOR]

Psychologically based interventions aim to improve pain-related functioning by targeting pain-related fears, cognitions and behaviors. Mediation and moderation analyses permit further examination of the effect of treatment on an outcome. This systematic review and meta-analysis aims to synthetize the evidence of specific mediators and moderators (i.e., treatment targets) of psychologically based treatment effects on pain and disability. A total of 28 mediation and 11 moderation analyses were included. Thirteen mediation studies were included in a meta-analysis, and the rest was narratively synthetized. Reductions in pain-related fear (indirect effect [IE]: −0.07; 95% confidence interval [CI]: −0.11, −0.04) and catastrophizing (IE: -0.07; 95%CI: −0.14, −0.00), as well as increases in self-efficacy (IE: -0.07; 95%CI: −0.11, −0.04), mediated effects of cognitive behavioral therapy on disability but not on pain intensity, when compared to control treatments. Enhancing pain acceptance (IE: -0.17; 95%CI: −0.31, −0.03) and psychological flexibility (IE: -0.30; 95%CI: −0.41, −0.18) mediated acceptance and commitment therapy effects on disability. The narrative synthesis showed conflicting evidence, which did not support a robust moderated effect for any of the examined constructs. Overall, the methodological quality regarding mediation was low, and some key pitfalls are highlighted alongside recommendations to provide a platform for future research. • Reductions in pain-related fear and catastrophizing and increases in self-efficacy mediate effects of CBT on disability but not on pain intensity. • Increases of pain acceptance and psychological flexibility mediate ACT effects on disability. • Still, there is limited evidence on the shared and separate mechanisms across the psychologically based interventions for pain. • Overall, the methodological quality of the available mediation literature is low. • Conflicting evidence does not support a robust moderated effect for any of the examined constructs. [ABSTRACT FROM AUTHOR]