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Background  Systematic reviews evaluating complex interventions often encounter substantial clinical heterogeneity in intervention components and implementation features making synthesis challenging. Qualitative comparative analysis (QCA) is a non-probabilistic method that uses mathematical set theory to study complex phenomena; it has been proposed as a potential method to complement traditional evidence synthesis in reviews of complex interventions to identify key intervention components or implementation features that might explain effectiveness or ineffectiveness. The objective of this study was to describe our approach in detail and examine the suitability of using QCA within the context of a systematic review.    Methods  We used data from a completed systematic review of behavioral interventions to improve medication adherence to conduct two substantive analyses using QCA. The first analysis sought to identify combinations of nine behavior change techniques/components (BCTs) found among effective interventions, and the second analysis sought to identify combinations of five implementation features (e.g., agent, target, mode, time span, exposure) found among effective interventions. For each substantive analysis, we reframed the review’s research questions to be designed for use with QCA, calibrated sets (i.e., transformed raw data into data used in analysis), and identified the necessary and/or sufficient combinations of BCTs and implementation features found in effective interventions.    Results  Our application of QCA for each substantive analysis is described in detail. We extended the original review findings by identifying seven combinations of BCTs and four combinations of implementation features that were sufficient for improving adherence. We found reasonable alignment between several systematic review steps and processes used in QCA except that typical approaches to study abstraction for some intervention components and features did not support a robust calibration for QCA.    Conclusions  QCA was suitable for use within a systematic review of medication adherence interventions and offered insights beyond the single dimension stratifications used in the original completed review. Future prospective use of QCA during a review is needed to determine the optimal way to efficiently integrate QCA into existing approaches to evidence synthesis of complex interventions.    Electronic supplementary material  The online version of this article (doi:10.1186/s13643-016-0256-y) contains supplementary material, which is available to authorized users.

Using qualitative comparative analysis in a systematic review of a complex intervention