A Noninterventional, Observational Sleep Study to Develop a Sleep Algorithm to Support a Digital Medicine System (Preprint)

BACKGROUND Sleep-wake patterns are important behavioral biomarkers for patients with serious mental illness (SMI), providing insight into their well-being. The gold standard for monitoring sleep is polysomnography (PSG), which requires a sleep lab facility; however, advances in wearable sensor technology allow for real-world sleep-wake monitoring. OBJECTIVE The goal of this study was to develop a PSG-validated sleep algorithm using accelerometer (ACC) and electrocardiogram (ECG) data from a wearable patch to accurately quantify sleep in a real-world setting. METHODS In this noninterventional, nonsignificant-risk, abbreviated investigational device exemption, single-site study, participants wore the reusable wearable sensor version 2 (RW2) patch. The RW2 patch is part of a digital medicine system (aripiprazole with sensor) designed to provide objective records of medication ingestion for patients with schizophrenia, bipolar I disorder, and major depressive disorder. This study developed a sleep algorithm from patch data and did not contain any study-related or digitized medication. Patch-acquired ACC and ECG data were compared against PSG data to build machine learning classification models to distinguish periods of wake from sleep. The PSG data provided sleep stage classifications at 30-second intervals, which were combined into 5-minute windows, and labeled as sleep or wake based on the majority of sleep stages within the window. ACC and ECG features were derived for each 5-minute window. The algorithm that most accurately predicted sleep parameters against PSG data was compared to commercially available wearable devices to further benchmark model performance. RESULTS Of 80 participants enrolled, 73 had at least 1 night of analyzable ACC and ECG data (31 healthy volunteers and 42 participants with diagnosed SMI). Overall, 10,170 5-minute valid windows were identified (5610 from participants with SMI) and 83% were classified as greater than half sleep. Of 3 models tested, the conditional random field (CRF) algorithm provided the most robust sleep-wake classification. Performance was comparable to the middle 50% of commercial devices evaluated in a recent publication, providing sleep detection performance of 0.93 (sensitivity) and wake detection performance of 0.60 (specificity) at a prediction probability threshold of 0.75. The CRF algorithm retained this performance for individual sleep parameters, including total sleep time, sleep efficiency, and wake after sleep onset (within the middle 50% to top 25% of the assessed devices). The only parameter where the model performance was lower was sleep onset latency (within the bottom 25% of all comparator devices). CONCLUSIONS Using industry-best practices, we developed a sleep algorithm for use with the RW2 patch that can accurately detect sleep and wake windows compared to PSG-labeled sleep data. This algorithm may be used for a more complete understanding of well-being for patients with SMI in a real-world setting, without the need for PSG and a sleep lab. CLINICALTRIAL NA