BackgroundSuicide is the second leading cause of death in adolescents, and self-harm is one of the strongest predictors of death by suicide. The rates of adolescents presenting to emergency departments (EDs) for suicidal thoughts and behaviors (STBs) have increased. Still, existing follow-up after ED discharge is inadequate, leaving a high-risk period for reattempts and suicide. There is a need for innovative evaluation of imminent suicide risk factors in these patients, focusing on continuous real-time evaluations with low assessment burden and minimal reliance on patient disclosure of suicidal intent.ObjectiveThis study examines prospective longitudinal associations between observed real-time mobile passive sensing, including communication and activity patterns, and clinical and self-reported assessments of STB over 6 months.MethodsThis study will include 90 adolescents recruited on their first outpatient clinic visit following their discharge from the ED due to a recent STB. Participants will complete brief weekly assessments and be monitored continuously for their mobile app usage, including mobility, activity, and communication patterns, over 6 months using the iFeel research app. Participants will complete 4 in-person visits for clinical assessment at baseline and at the 1-, 3-, and 6-month follow-ups. The digital data will be processed, involving feature extraction, scaling, selection, and dimensionality reduction. Passive monitoring data will be analyzed using both classical machine learning models and deep learning models to identify proximal associations between real-time observed communication, activity patterns, and STB. The data will be split into a training and validation data set, and predictions will be matched against the clinical evaluations and self-reported STB events (ie, labels). To use both labeled and unlabeled digital data (ie, passively collected), we will use semisupervised methods in conjunction with a novel method that is based on anomaly detection notions.ResultsParticipant recruitment and follow-up started in February 2021 and are expected to be completed by 2024. We expect to find prospective proximal associations between mobile sensor communication, activity data, and STB outcomes. We will test predictive models for suicidal behaviors among high-risk adolescents.ConclusionsDeveloping digital markers of STB in a real-world sample of high-risk adolescents presenting to ED can inform different interventions and provide an objective means to assess the risk of suicidal behaviors. The results of this study will be the first step toward large-scale validation that may lead to suicide risk measures that aid psychiatric follow-up, decision-making, and targeted treatments. This novel assessment could facilitate timely identification and intervention to save young people’s lives.International Registered Report Identifier (IRRID)DERR1-10.2196/46464