Digital Biomarkers最新文献

Introduction: Parkinson's disease (PD) is poorly quantified by patients outside the clinic, and paper diaries have problems with subjective descriptions and bias. Wearable sensor platforms; however, can accurately quantify symptoms such as tremor, dyskinesia, and bradykinesia. Commercially available smartwatches are equipped with accelerometers and gyroscopes that can measure motion for objective evaluation. We sought to evaluate the clinical utility of a prescription smartwatch-based monitoring system for PD utilizing periodic task-based motor assessment.

Methods: Sixteen patients with PD used a smartphone- and smartwatch-based monitoring system to objectively assess motor symptoms for 1 week prior to instituting a doctor recommended change in therapy and for 4 weeks after the change. After 5 weeks the participants returned to the clinic to discuss their results with their doctor, who made therapy recommendations based on the reports and his clinical judgment. Symptom scores were synchronized with the medication diary and the temporal effects of therapy on weekly and hourly timescales were calculated.

Results: Thirteen participants successfully completed the study and averaged 4.9 assessments per day for 3 days per week during the study. The doctor instructed 8 participants to continue their new regimens and 5 to revert to their previous regimens. The smartwatch-based assessments successfully captured intraday fluctuations and short- and long-term responses to therapies, including detecting significant improvements (p < 0.05) in at least one symptom in 7 participants.

Conclusions: The smartwatch-based app successfully captured temporal trends in symptom scores following application of new therapy on hourly, daily, and weekly timescales. These results suggest that validated smartwatch-based PD monitoring can provide clinically relevant information and may reduce the need for traditional office visits for therapy adjustment.

The development of novel digital endpoints (NDEs) using digital health technologies (DHTs) may provide opportunities to transform drug development. It requires a multidisciplinary, multi-study approach with strategic planning and a regulatory-guided pathway to achieve regulatory and clinical acceptance. Many NDEs have been explored; however, success has been limited. To advance industry use of NDEs to support drug development, we outline a theoretical, methodological study as a use-case proposal to describe the process and considerations when developing and obtaining regulatory acceptance for an NDE to assess sleep in patients with rheumatoid arthritis (RA). RA patients often suffer joint pain, fatigue, and sleep disturbances (SDs). Although many researchers have investigated the mobility of joint functions using wearable technologies, the research of SD in RA has been limited due to the availability of suitable technologies. We proposed measuring the improvement of sleep as the novel endpoint for an anti-TNF therapy and described the meaningfulness of the measure, considerations of tool selection, and the design of clinical validation. The recommendations from the FDA patient-focused drug development guidance, the Clinical Trials Transformation Initiative (CTTI) pathway for developing novel endpoints from DHTs, and the V3 framework developed by the Digital Medicine Society (DiMe) have been incorporated in the proposal. Regulatory strategy and engagement pathways are also discussed.

Background: Functional outcome measures used to assess efficacy in clinical trials of investigational treatments for rare neuromuscular diseases like Duchenne muscular dystrophy (DMD) are performance-based tasks completed by the patient during hospital visits. These are prone to bias and may not reflect motor abilities in real-world settings. Digital tools, such as wearable devices and other remote sensors, provide the opportunity for continuous, objective, and sensitive measurements of functional ability during daily life. Maintaining ambulation is of key importance to individuals with DMD. Stride velocity 95th centile (SV95C) is the first wearable acquired digital endpoint to receive qualification from the European Medicines Agency (EMA) to quantify the ambulation ability of ambulant DMD patients aged ≥5 years in drug therapeutic studies; it is also currently under review for the US Food and Drug Administration (FDA) qualification.

Summary: Focusing on SV95C as a key example, we describe perspectives of multiple stakeholders on the promise of novel digital endpoints in neuromuscular disease drug development.

This viewpoint focuses on the ways in which digital medicine and measurement-based care can be utilized in tandem to promote better assessment, patient engagement, and an improved quality of psychiatric care. To date, there has been an underutilization of digital measurement in psychiatry, and there is little discussion of the feedback and patient engagement process in digital medicine. Measurement-based care is a recognized evidence-based strategy that engages patients in an understanding of their outcome data. When implemented as designed, providers review the scores and trends in outcome immediately and then provide feedback to their patients. However, the process is typically confined to office visits, which does not provide a complete picture of a patient's progress and functioning. The process is labor intensive, even with digital feedback systems, but the integration of passive metrics obtained through wearables and apps can supplement office-based observations. This enhanced measurement-based care process can provide a picture of real-world patient functioning through passive metrics (activity, sleep, etc.). This can potentially engage patients more in their health data and involve a critically needed therapeutic alliance component in digital medicine.

Introduction: Difficulty swallowing (dysphagia) occurs frequently in patients with neurological disorders and can lead to aspiration, choking, and malnutrition. Dysphagia is typically diagnosed using costly, invasive imaging procedures or subjective, qualitative bedside examinations. Wearable sensors are a promising alternative to noninvasively and objectively measure physiological signals relevant to swallowing. An ongoing challenge with this approach is consolidating these complex signals into sensitive, clinically meaningful metrics of swallowing performance. To address this gap, we propose 2 novel, digital monitoring tools to evaluate swallows using wearable sensor data and machine learning.

Methods: Biometric swallowing and respiration signals from wearable, mechano-acoustic sensors were compared between patients with poststroke dysphagia and nondysphagic controls while swallowing foods and liquids of different consistencies, in accordance with the Mann Assessment of Swallowing Ability (MASA). Two machine learning approaches were developed to (1) classify the severity of impairment for each swallow, with model confidence ratings for transparent clinical decision support, and (2) compute a similarity measure of each swallow to nondysphagic performance. Task-specific models were trained using swallow kinematics and respiratory features from 505 swallows (321 from patients and 184 from controls).

Results: These models provide sensitive metrics to gauge impairment on a per-swallow basis. Both approaches demonstrate intrasubject swallow variability and patient-specific changes which were not captured by the MASA alone. Sensor measures encoding respiratory-swallow coordination were important features relating to dysphagia presence and severity. Puree swallows exhibited greater differences from controls than saliva swallows or liquid sips (p < 0.037).

Discussion: Developing interpretable tools is critical to optimize the clinical utility of novel, sensor-based measurement techniques. The proof-of-concept models proposed here provide concrete, communicable evidence to track dysphagia recovery over time. With refined training schemes and real-world validation, these tools can be deployed to automatically measure and monitor swallowing in the clinic and community for patients across the impairment spectrum.

Background: Prior studies suggest that participation in rehabilitation exercises improves motor function poststroke; however, studies on optimal exercise dose and timing have been limited by the technical challenge of quantifying exercise activities over multiple days.

Objectives: The objectives of this study were to assess the feasibility of using body-worn sensors to track rehabilitation exercises in the inpatient setting and investigate which recording parameters and data analysis strategies are sufficient for accurately identifying and counting exercise repetitions.

Methods: MC10 BioStampRC® sensors were used to measure accelerometer and gyroscope data from upper extremities of healthy controls (n = 13) and individuals with upper extremity weakness due to recent stroke (n = 13) while the subjects performed 3 preselected arm exercises. Sensor data were then labeled by exercise type and this labeled data set was used to train a machine learning classification algorithm for identifying exercise type. The machine learning algorithm and a peak-finding algorithm were used to count exercise repetitions in non-labeled data sets.

Results: We achieved a repetition counting accuracy of 95.6% overall, and 95.0% in patients with upper extremity weakness due to stroke when using both accelerometer and gyroscope data. Accuracy was decreased when using fewer sensors or using accelerometer data alone.

Conclusions: Our exploratory study suggests that body-worn sensor systems are technically feasible, well tolerated in subjects with recent stroke, and may ultimately be useful for developing a system to measure total exercise "dose" in poststroke patients during clinical rehabilitation or clinical trials.

Background: The life science industry has a strong interest in real-world data (RWD), a term that is currently being used in many ways and with varying definitions depending on the source. In this review article, we provide a summary overview of the challenges and risks regarding the use of RWD and its translation into real-world evidence and provide a classification and visualization of RWD challenges by means of the RWD Challenges Radar.

Summary: Based on a systematic literature search, we identified 3 types of challenges - organizational, technological, and people-based - that must be addressed when deriving evidence from RWD to be used in drug approval and other applications. It further demonstrates that numerous different aspects, for example, related to the application field and the associated industry, must be considered. A key finding in our review is that the regulatory landscape must be carefully assessed before utilizing RWD.

Key messages: Establishing awareness and insight into the challenges and risks regarding the use of RWD will be key to taking full advantage of the RWD potential. As a result of this review, an "RWD Challenges Radar" will support the establishment of awareness by providing a comprehensive overview of the relevant aspects to be considered when employing RWD.

The EVIDENCE (EValuatIng connecteD sENsor teChnologiEs) checklist was developed by a multidisciplinary group of content experts convened by the Digital Medicine Society, representing the clinical sciences, data management, technology development, and biostatistics. The aim of EVIDENCE is to promote high quality reporting in studies where the primary objective is an evaluation of a digital measurement product or its constituent parts. Here we use the terms digital measurement product and connected sensor technology interchangeably to refer to tools that process data captured by mobile sensors using algorithms to generate measures of behavioral and/or physiological function. EVIDENCE is applicable to 5 types of evaluations: (1) proof of concept; (2) verification, (3) analytical validation, and (4) clinical validation as defined by the V3 framework; and (5) utility and usability assessments. Using EVIDENCE, those preparing, reading, or reviewing studies evaluating digital measurement products will be better equipped to distinguish necessary reporting requirements to drive high-quality research. With broad adoption, the EVIDENCE checklist will serve as a much-needed guide to raise the bar for quality reporting in published literature evaluating digital measurements products.

Digital health has been rapidly thrust into the forefront of care delivery. Poised to extend the clinician's reach, a new set of examination tools will redefine neurologic and neurosurgical care, serving as the basis for the digital neurologic examination. We describe its components and review specific technologies, which move beyond traditional video-based telemedicine encounters and include separate digital tools. A future suite of these clinical assessment technologies will blur the lines between history taking, examination, and remote monitoring. Prior to full-scale implementation, however, much more investigation is needed. Because of the nascent state of the technologies, researchers, clinicians, and developers should establish digital neurologic examination requirements in order to maximize its impact.

Clinical safety findings remain one of the reasons for attrition of drug candidates during clinical development. Cardiovascular liabilities are not consistently detected in early-stage clinical trials and often become apparent when drugs are administered chronically for extended periods of time. Vital sign data collection outside of the clinic offers an opportunity for deeper physiological characterization of drug candidates and earlier safety signal detection. A working group representing expertise from biopharmaceutical and technology sectors, US Food and Drug Administration (FDA) public-private partnerships, academia, and regulators discussed and presented a remote cardiac monitoring case study at the FNIH Biomarkers Consortium Remote Digital Monitoring for Medical Product Development workshop to examine applicability of the biomarker qualification evidentiary framework by the FDA. This use case examined the components of the framework, including the statement of need, the context of use, the state of the evidence, and the benefit/risk profile. Examination of results from 2 clinical trials deploying 510(k)-cleared devices for remote cardiac data collection demonstrated the need for analytical and clinical validity irrespectively of the regulatory status of a device of interest, emphasizing the importance of data collection method assessment in the context of intended use. Additionally, collection of large amounts of ambulatory data also highlighted the need for new statistical methods and contextual information to enable data interpretation. A wider adoption of this approach for drug development purposes will require collaborations across industry, academia, and regulatory agencies to establish methodologies and supportive data sets to enable data interpretation and decision-making.