Developing a multivariable prediction model to support personalized selection among five major empirically-supported treatments for adult depression. Study protocol of a systematic review and individual participant data network meta-analysis

Background: Various treatments are recommended as first-line options in practice guidelines for depression, but it is unclear which is most efficacious for a given person. Accurate individualized predictions of relative treatment effects are needed to optimize treatment recommendations for depression and reduce this disorder’s vast personal and societal costs. Aims: We describe the protocol for a systematic review and individual participant data (IPD) network meta-analysis (NMA) to inform personalized treatment selection among five major empirically-supported depression treatments. Method: We will use the METASPY database to identify randomized clinical trials that compare two or more of five treatments for adult depression: antidepressant medication, cognitive therapy, behavioral activation, interpersonal psychotherapy, and psychodynamic therapy. We will request IPD from identified studies. We will conduct an IPD-NMA and develop a multivariable prediction model that estimates individualized relative treatment effects from demographic, clinical, and psychological participant characteristics. Depressive symptom level at treatment completion will constitute the primary outcome. We will evaluate this model using a range of measures for discrimination and calibration, and examine its potential generalizability using internal-external cross-validation. Conclusions: We describe a state-of-the-art method to predict personalized treatment effects based on IPD from multiple trials. The resulting prediction model will need prospective evaluation in mental health care for its potential to inform shared decision-making. This study will result in a unique database of IPD from randomized clinical trials around the world covering five widely used depression treatments, available for future research.