BackgroundMajor depressive disorder (MDD) is a serious public health concern worldwide. A treatment approach that incorporates measurement-based care (MBC) and shared decision-making between patients with MDD and their providers may foster patient engagement and improve clinical outcomes. While digital tools such as mobile apps show promise for expanding health interventions, these apps are rarely integrated into clinical practice.ObjectiveThe primary objective of this ongoing study is to determine whether implementation of a digital tool—thePathway Platform—in primary care improves adherence to MBC practices; here, we present the study methods.MethodsThis large-scale, real-world implementation study is based on a pilot study of an earlier iteration of a mobile app (thePathway app) that confirmed the feasibility of using the app in patients with MDD and showed a positive trend in patient engagement in the app arm. In addition, a user-centered design approach that included qualitative assessments from patients and providers was used to improve understanding of the patient journey and care team workflows. User feedback highlighted the need for enhanced features, education modules, and real-time data sharing via integration with the electronic health record. The current iteration of thePlatformincludes the newest version of thePathway app, education modules for both patients and providers, and real-time patient-level data sharing with the electronic health record. The study takes place in primary care sites within the Advocate Aurora Health system in Illinois and includes adult patients with MDD who were recently prescribed monotherapy antidepressant medication (defined as a new start, medication switch, or dose change in the past 3 months). Clinical performance and selected patient outcomes will be compared before and after the implementation of thePlatform.ResultsPatient recruitment was completed in July 2022, with initial results expected in mid-2023.ConclusionsThis study will provide useful insights into real-world integration of a digital platform within a large health system. The methods presented here highlight the unique user-centric development of thePathway Platform, which has resulted in an enhanced digital tool with the potential to foster MBC and shared decision-making, improve patient-provider communication, and ultimately lead to optimized treatment outcomes for patients with MDD.Trial RegistrationClinicalTrials.gov NCT04891224; https://clinicaltrials.gov/ct2/show/NCT04891224International Registered Report Identifier (IRRID)DERR1-10.2196/43788