Patient-oriented Randomized Pragmatic Feasibility Trial With rTMS in Depression and Anxiety

The overarching goal of this trial is to evaluate whether a definite adaptive pragmatic trial would be feasible and establish clear go/no-go criteria as to whether proceeding to such definite trial is feasible. Specific aims include 1) testing the feasibility of recruiting a sample of TRD patients with less strict inclusion and exclusion criteria; 2) comparing different depression and anxiety scales (both clinician-rated and self-rated) and seek input from patients regarding their preferences; 3) seek input from patients with regards to the use of digital phenotyping as a tool to investigate biomarkers as well as engaging in the design of a potential implementation of such biomarker in a future definite trial. Aim 1. To evaluate the feasibility of a future definite adaptive pragmatic RCT comparing left vs right DLPFC repetitive transcranial magnetic stimulation (rTMS) in TRD. Hypothesis 1a: Enrollment will be 70% of the planned target over the 1-year recruitment period. Hypothesis 1b: Retention rate of randomized participants will be ≥70% at the end of the intervention in both groups. Aim 2. To evaluate patients' preferences regarding information about treatment options when there is no response to allocated treatment. Hypothesis 2: Patients will prefer to modify treatment when there is no response. Aim 3. To assess the feasibility of digital phenotyping as an tool to investigate biomarkers in TRD. Hypothesis 3a: Survey uptake and participation in the study regarding the use of digital phenotyping will be 80% of randomized participants. Hypothesis 3b: Of those survey responders, 75% will indicate they would consent to digital phenotyping in a future definite RCT. Aim 4. To develop a Bayesian statistical model that continuously updates personalized treatment effect estimates as the trial progresses, and identify the circumstances under which use of the model in a full-scale trial could inform treatment choice as the trial progresses. Hypothesis 4: The modeling results will identify at least one subgroup for whom early stopping of the definitive trial in that subgroup may be warranted.