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Nuisance mediators and missing data in mediation analyses of pain trials

This journal recently published a paper by O'Neill and colleagues, entitled "Examining what factors mediate treatment effect in chronic low back pain: a mediation analysis of a Cognitive Functional Therapy clinical trial” (O’Neill, O’Sullivan, O’Sullivan, Purtill, & O’Keeffe, 2020). Although the limitations in O'Neill et al. preclude robust conclusions about the mechanisms of Cognitive Functional Therapy (CFT), their study highlights wider issues for understanding treatment mechanisms for chronic pain. This commentary focuses on two issues: the need for mediation analyses to explain why treatments do not work, and the misreporting of missing data in mediation analyses.