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Continuous, objective monitoring of motor signs and symptoms may help improve tracking of disease progression and treatment response in Parkinson’s disease (PD). This study assessed the analytical and clinical validity of multi-sensor smartwatch measurements in hospitalized and home-based settings (96 patients with PD; mean wear time 19 h/day) using a twice-daily virtual motor examination (VME) at times representing medication OFF/ON states. Digital measurement performance was better during inpatient clinical assessments for composite V-scores than single-sensor–derived features for bradykinesia (Spearman |r|= 0.63, reliability = 0.72), tremor (|r|= 0.41, reliability = 0.65), and overall motor features (|r|= 0.70, reliability = 0.67). Composite levodopa effect sizes during hospitalization were 0.51–1.44 for clinical assessments and 0.56–1.37 for VMEs. Reliability of digital measurements during home-based VMEs was 0.62–0.80 for scores derived from weekly averages and 0.24–0.66 for daily measurements. These results show that unsupervised digital measurements of motor features with wrist-worn sensors are sensitive to medication state and are reliable in naturalistic settings. Trial Registration: Japan Pharmaceutical Information Center Clinical Trials Information (JAPIC-CTI): JapicCTI-194825; Registered June 25, 2019.

Sensor-based remote monitoring could help better track Parkinson’s disease (PD) progression, and measure patients’ response to putative disease-modifying therapeutic interventions. To be useful, the remotely-collected measurements should be valid, reliable, and sensitive to change, and people with PD must engage with the technology. We developed a smartwatch-based active assessment that enables unsupervised measurement of motor signs of PD. Participants with early-stage PD ( N  = 388, 64% men, average age 63) wore a smartwatch for a median of 390 days. Participants performed unsupervised motor tasks both in-clinic (once) and remotely (twice weekly for one year). Dropout rate was 5.4%. Median wear-time was 21.1 h/day, and 59% of per-protocol remote assessments were completed. Analytical validation was established for in-clinic measurements, which showed moderate-to-strong correlations with consensus MDS-UPDRS Part III ratings for rest tremor (⍴ = 0.70), bradykinesia (⍴ = −0.62), and gait (⍴ = −0.46). Test-retest reliability of remote measurements, aggregated monthly, was good-to-excellent (ICC = 0.75–0.96). Remote measurements were sensitive to the known effects of dopaminergic medication (on vs off Cohen’s d = 0.19–0.54). Of note, in-clinic assessments often did not reflect the patients’ typical status at home. This demonstrates the feasibility of smartwatch-based unsupervised active tests, and establishes the analytical validity of associated digital measurements. Weekly measurements provide a real-life distribution of disease severity, as it fluctuates longitudinally. Sensitivity to medication-induced change and improved reliability imply that these methods could help reduce sample sizes needed to demonstrate a response to therapeutic interventions or disease progression.

Consumer wearables and sensors are a rich source of data about patients’ daily disease and symptom burden, particularly in the case of movement disorders like Parkinson’s disease (PD). However, interpreting these complex data into so-called digital biomarkers requires complicated analytical approaches, and validating these biomarkers requires sufficient data and unbiased evaluation methods. Here we describe the use of crowdsourcing to specifically evaluate and benchmark features derived from accelerometer and gyroscope data in two different datasets to predict the presence of PD and severity of three PD symptoms: tremor, dyskinesia, and bradykinesia. Forty teams from around the world submitted features, and achieved drastically improved predictive performance for PD status (best AUROC = 0.87), as well as tremor- (best AUPR = 0.75), dyskinesia- (best AUPR = 0.48) and bradykinesia-severity (best AUPR = 0.95).

Digital measures of walking and sedentariness may objectively quantify Parkinson’s disease (PD) progression. We analyzed longitudinal wearable-sensor data to evaluate the sensitivity and specificity of digital walking and non-walking measures in ambulatory people with PD. We selected 26 individual and 6 composite measures with sufficient sensitivity and test-retest reliability in a development dataset ( N  = 171). Twenty measures showed significant within-participant changes, and 7 showed larger 2-year effect-size than gold-standard clinical measures in people with early-stage PD ( N  = 101, mean number of years since diagnosis [YSD], 2.2). Significant changes in non-walking and composite measures were detectable as early as 10 months. Twelve measures showed greater change in people with more advanced PD ( N  = 67; mean YSD 6.5) compared to matched non-PD individuals ( N  = 171). Sensitivity and specificity results indicate that measures capturing walking and especially non-walking behaviors hold promise as PD progression markers in early to mid-stage PD.

Measuring the amount of physical activity and its patterns using wearable sensor technology in real-world settings can provide critical insights into health status. This study's aim was to develop and evaluate the analytical validity and transdemographic generalizability of an algorithm that classifies binary ambulatory status (yes or no) on the accelerometer signal from wrist-worn biometric monitoring technology. Biometric monitoring technology algorithm validation traditionally relies on large numbers of self-reported labels or on periods of high-resolution monitoring with reference devices. We used both methods on data collected from 2 distinct studies for algorithm training and testing, one with precise ground-truth labels from a reference device (n=75) and the second with participant-reported ground-truth labels from a more diverse, larger sample (n=1691); in total, we collected data from 16.7 million 10-second epochs. We trained a neural network on a combined data set and measured performance in multiple held-out testing data sets, overall and in demographically stratified subgroups. The algorithm was accurate at classifying ambulatory status in 10-second epochs (area under the curve 0.938; 95% CI 0.921-0.958) and on daily aggregate metrics (daily mean absolute percentage error 18%; 95% CI 15%-20%) without significant performance differences across subgroups. Our algorithm can accurately classify ambulatory status with a wrist-worn device in real-world settings with generalizability across demographic subgroups. The validated algorithm can effectively quantify users' walking activity and help researchers gain insights on users' health status.

Mobility is a meaningful aspect of an individual's health whose quantification can provide clinical insights. Wearable sensor technology can quantify walking behaviors (a key aspect of mobility) through continuous passive monitoring. Our objective was to characterize the analytical performance (accuracy and reliability) of a suite of digital measures of walking behaviors as critical aspects in the practical implementation of digital measures into clinical studies. We collected data from a wrist-worn device (the Verily Study Watch) worn for multiple days by a cohort of volunteer participants without a history of gait or walking impairment in a real-world setting. On the basis of step measurements computed in 10-second epochs from sensor data, we generated individual daily aggregates (participant-days) to derive a suite of measures of walking: step count, walking bout duration, number of total walking bouts, number of long walking bouts, number of short walking bouts, peak 30-minute walking cadence, and peak 30-minute walking pace. To characterize the accuracy of the measures, we examined agreement with truth labels generated by a concurrent, ankle-worn, reference device (Modus StepWatch 4) with known low error, calculating the following metrics: intraclass correlation coefficient (ICC), Pearson r coefficient, mean error, and mean absolute error. To characterize the reliability, we developed a novel approach to identify the time to reach a reliable readout (time to reliability) for each measure. This was accomplished by computing mean values over aggregation scopes ranging from 1 to 30 days and analyzing test-retest reliability based on ICCs between adjacent (nonoverlapping) time windows for each measure. In the accuracy characterization, we collected data for a total of 162 participant-days from a testing cohort (n=35 participants; median observation time 5 days). Agreement with the reference device-based readouts in the testing subcohort (n=35) for the 8 measurements under evaluation, as reflected by ICCs, ranged between 0.7 and 0.9; Pearson r values were all greater than 0.75, and all reached statistical significance (P<.001). For the time-to-reliability characterization, we collected data for a total of 15,120 participant-days (overall cohort N=234; median observation time 119 days). All digital measures achieved an ICC between adjacent readouts of >0.75 by 16 days of wear time. We characterized the accuracy and reliability of a suite of digital measures that provides comprehensive information about walking behaviors in real-world settings. These results, which report the level of agreement with high-accuracy reference labels and the time duration required to establish reliable measure readouts, can guide the practical implementation of these measures into clinical studies. Well-characterized tools to quantify walking behaviors in research contexts can provide valuable clinical information about general population cohorts and patients with specific conditions.

Psychiatric trials have some of the lowest success rates across therapeutic areas, resulting in decreased investment in psychopharmacological drug development even as the need for more effective treatments grows. Digital measures and digital biomarkers (DBMs) provide one potential avenue for ameliorating three of the largest problems impeding clinical trial success in psychiatry: diagnostic heterogeneity, endpoint subjectivity, and high placebo response rates. First, DBMs may address heterogeneity and comorbidity in psychiatric nosology by identifying predictive DBMs of treatment response via the targeting of drugs to psychiatric subtypes. Second, DBMs can provide objective measures of physiology and behavior that when grounded in meaningful aspects of health (MAH) could support use for regulatory decision-making. By objectively and continuously measuring aspects of a patient’s disease that the patient wants to improve or prevent from getting worse, DBMs might provide clinical trial endpoints that are more sensitive to treatment effects as compared to traditional clinician-reported outcomes. Lastly, DBMs could help address challenges surrounding high placebo response rates. Development of predictive DBMs of placebo response may allow for improved enrichment study designs to reduce placebo response. Objective digital measures may also be more robust against the placebo effect and offer an improved study endpoint alternative. Successful deployment of DBMs to address the historical challenges facing psychiatric drug trials will require close collaboration between industry, academic, and regulatory partners.

Analyzing the cardiovascular system condition via Electrocardiography (ECG) is a common and highly effective approach, and it has been practiced and perfected over many decades. ECG sensing is non-invasive and relatively easy to acquire, and yet it is still cumbersome for holter monitoring tests that may span over hours and even days. A possible alternative in this context is Photoplethysmography (PPG): An optically-based signal that measures blood volume fluctuations, as typically sensed by conventional ``wearable devices''. While PPG presents clear advantages in acquisition, convenience, and cost-effectiveness, ECG provides more comprehensive information, allowing for a more precise detection of heart conditions. This implies that a conversion from PPG to ECG, as recently discussed in the literature, inherently involves an unavoidable level of uncertainty. In this paper we introduce a novel methodology for addressing the PPG-2-ECG conversion, and offer an enhanced classification of cardiovascular conditions using the given PPG, all while taking into account the uncertainties arising from the conversion process. We provide a mathematical justification for our proposed computational approach, and present empirical studies demonstrating its superior performance compared to state-of-the-art baseline methods.