The Appalachia Mind Health Initiative (AMHI): a pragmatic randomized clinical trial of adjunctive internet-based cognitive behavior therapy for treating major depressive disorder among primary care patients.

BACKGROUND: Major depressive disorder (MDD) is a leading cause of disease morbidity. Combined treatment with antidepressant medication (ADM) plus psychotherapy yields a much higher MDD remission rate than ADM only. But 77% of US MDD patients are nonetheless treated with ADM only despite strong patient preferences for psychotherapy. This mismatch is due at least in part to a combination of cost considerations and limited availability of psychotherapists, although stigma and reluctance of PCPs to refer patients for psychotherapy are also involved. Internet-based cognitive behaviorial therapy (i-CBT) addresses all of these problems. METHODS: Enrolled patients (n = 3360) will be those who are beginning ADM-only treatment of MDD in primary care facilities throughout West Virginia, one of the poorest and most rural states in the country. Participating treatment providers and study staff at West Virginia University School of Medicine (WVU) will recruit patients and, after obtaining informed consent, administer a baseline self-report questionnaire (SRQ) and then randomize patients to 1 of 3 treatment arms with equal allocation: ADM only, ADM + self-guided i-CBT, and ADM + guided i-CBT. Follow-up SRQs will be administered 2, 4, 8, 13, 16, 26, 39, and 52 weeks after randomization. The trial has two primary objectives: to evaluate aggregate comparative treatment effects across the 3 arms and to estimate heterogeneity of treatment effects (HTE). The primary outcome will be episode remission based on a modified version of the patient-centered Remission from Depression Questionnaire (RDQ). The sample was powered to detect predictors of HTE that would increase the proportional remission rate by 20% by optimally assigning individuals as opposed to randomly assigning them into three treatment groups of equal size. Aggregate comparative treatment effects will be estimated using intent-to-treat analysis methods. Cumulative inverse probability weights will be used to deal with loss to follow-up. A wide range of self-report predictors of MDD heterogeneity of treatment effects based on previous studies will be included in the baseline SRQ. A state-of-the-art ensemble machine learning method will be used to estimate HTE. DISCUSSION: The study is innovative in using a rich baseline assessment and in having a sample large enough to carry out a well-powered analysis of heterogeneity of treatment effects. We anticipate finding that self-guided and guided i-CBT will both improve outcomes compared to ADM only. We also anticipate finding that the comparative advantages of adding i-CBT to ADM will vary significantly across patients. We hope to develop a stable individualized treatment rule that will allow patients and treatment providers to improve aggregate treatment outcomes by deciding collaboratively when ADM treatment should be augmented with i-CBT. TRIAL REGISTRATION: ClinicalTrials.gov NCT04120285 . Registered on October 19, 2019.

Balancing vs modeling approaches to weighting in practice.

There are two seemingly unrelated approaches to weighting in observational studies. One of them maximizes the fit of a model for treatment assignment to then derive weights-we call this the modeling approach. The other directly optimizes certain features of the weights-we call this the balancing approach. The implementations of these two approaches are related: the balancing approach implicitly models the propensity score, while instances of the modeling approach impose balance conditions on the covariates used to estimate the propensity score. In this article, we review and compare these two approaches to weighting. Previous review papers have focused on the modeling approach, emphasizing the importance of checking covariate balance. However, as we discuss, the dispersion of the weights is another important aspect of the weights to consider, in addition to the representativeness of the weighted sample and the sample boundedness of the weighted estimator. In particular, the dispersion of the weights is important because it translates into a measure of effective sample size, which can be used to select between alternative weighting schemes. In this article, we examine the balancing approach to weighting, discuss recent methodological developments, and compare instances of the balancing and modeling approaches in a simulation study and an empirical study. In practice, unless the treatment assignment model is known, we recommend using the balancing approach to weighting, as it systematically results in better covariate balance with weights that are minimally dispersed. As a result, effect estimates tend to be more accurate and stable.