Ieuan Clay

Introduction: Incorporating outcome measures that assess the most impactful symptoms is a priority for clinical trials. We qualitatively examined whether caregivers of individuals with Rett syndrome deemed breathing dysfunction as a meaningful and measurable aspect of health. Methods: We conducted semi-structured interviews (N = 13) with caregivers of individuals with Rett syndrome followed by thematic analysis grounded in theory to examine themes. Results: Themes and subthemes for experiences with breathing dysfunction emerged: (1) meaningfulness; (2) impact; and (3) connecting with other symptoms. Two themes for preferences for digitally measuring breathing dysfunction emerged: (1) conditional willingness and (2) benefits of digital measurement. Conclusion: Caregivers reported that breathing dysfunction was meaningful and measurable and had significant impacts on their child’s lives as well as theirs and their families. This study lays the groundwork for guiding the development of novel measures and outcomes within future clinical trials managing breathing dysfunction in Rett syndrome.

Background: As the number of cancer survivors increases, maintaining health-related quality of life in cancer survivorship is a priority. This necessitates accurate and reliable methods to assess how cancer survivors are feeling and functioning. Real-world digital measures derived from wearable sensors offer potential for monitoring well-being and physical function in cancer survivorship, but questions surrounding the clinical utility of these measures remain to be answered. Objective: In this secondary analysis, we used 2 existing data sets to examine how measures of real-world physical behavior, captured with a wearable accelerometer, were related to aerobic fitness and self-reported well-being and physical function in a sample of individuals who had completed cancer treatment. Methods: Overall, 86 disease-free cancer survivors aged 21-85 years completed self-report assessments of well-being and physical function, as well as a submaximal exercise test that was used to estimate their aerobic fitness, quantified as predicted submaximal oxygen uptake (VO2). A thigh-worn accelerometer was used to monitor participants’ real-world physical behavior for 7 days. Accelerometry data were used to calculate average values of the following measures of physical behavior: sedentary time, step counts, time in light and moderate to vigorous physical activity, time and weighted median cadence in stepping bouts over 1 minute, and peak 30-second cadence. Results: Spearman correlation analyses indicated that 6 (86%) of the 7 accelerometry-derived measures of real-world physical behavior were not significantly correlated with Functional Assessment of Cancer Therapy-General total well-being or linked Patient-Reported Outcomes Measurement Information System-Physical Function scores (Ps≥.08). In contrast, all but one of the physical behavior measures were significantly correlated with submaximal VO2 (Ps≤.03). Comparing these associations using likelihood ratio tests, we found that step counts, time in stepping bouts over 1 minute, and time in moderate to vigorous activity were more strongly associated with submaximal VO2 than with self-reported well-being or physical function (Ps≤.03). In contrast, cadence in stepping bouts over 1 minute and peak 30-second cadence were not more associated with submaximal VO2 than with the self-reported measures (Ps≥.08). Conclusions: In a sample of disease-free cancer survivors, we found that several measures of real-world physical behavior were more associated with aerobic fitness than with self-reported well-being and physical function. These results highlight the possibility that in individuals who have completed cancer treatment, measures of real-world physical behavior may provide additional information compared with self-reported and performance measures. To advance the appropriate use of digital measures in oncology clinical research, further research evaluating the clinical utility of real-world physical behavior over time in large, representative samples of cancer survivors is warranted. Trial Registration: ClinicalTrials.gov NCT03781154; https://clinicaltrials.gov/ct2/show/NCT03781154

Digital health technologies (DHTs) have the potential to modernize drug development and clinical trial operations by remotely, passively, and continuously collecting ecologically valid evidence that is meaningful to patients’ lived experiences. Such evidence holds potential for all drug development stakeholders, including regulatory agencies, as it will help create a stronger evidentiary link between approval of new therapeutics and the ultimate aim of improving patient lives. However, only a very small number of novel digital measures have matured from exploratory usage into regulatory qualification or efficacy endpoints. This shows that despite the clear potential, actually gaining regulatory agreement that a new measure is both fit-for-purpose and delivers value remains a serious challenge. One of the key stumbling blocks for developers has been the requirement to demonstrate that a digital measure is meaningful to patients. This viewpoint aims to examine the co-evolution of regulatory guidance in the United States (U.S.) and best practice for integration of DHTs into the development of clinical outcome assessments. Contextualizing guidance on meaningfulness within the larger shift towards a patient-centric drug development approach, this paper reviews the U.S. Food and Drug Administration (FDA) guidance and existing literature surrounding the development of meaningful digital measures and patient engagement, including the recent examples of rejections by the FDA that further emphasize patient-centricity in digital measures. Finally, this paper highlights remaining hurdles and provides insights into the established frameworks for development and adoption of digital measures in clinical research.

BACKGROUND As the number of cancer survivors increases, maintaining health-related quality of life in cancer survivorship is a priority. This necessitates accurate and reliable methods to assess how cancer survivors are feeling and functioning. Real-world digital measures derived from wearable sensors offer potential for monitoring well-being and physical function in cancer survivorship, but questions surrounding the clinical utility of these measures remain to be answered. OBJECTIVE In this secondary analysis, we used 2 existing data sets to examine how measures of real-world physical behavior, captured with a wearable accelerometer, were related to aerobic fitness and self-reported well-being and physical function in a sample of individuals who had completed cancer treatment. METHODS Overall, 86 disease-free cancer survivors aged 21-85 years completed self-report assessments of well-being and physical function, as well as a submaximal exercise test that was used to estimate their aerobic fitness, quantified as predicted submaximal oxygen uptake (VO2). A thigh-worn accelerometer was used to monitor participants’ real-world physical behavior for 7 days. Accelerometry data were used to calculate average values of the following measures of physical behavior: sedentary time, step counts, time in light and moderate to vigorous physical activity, time and weighted median cadence in stepping bouts over 1 minute, and peak 30-second cadence. RESULTS Spearman correlation analyses indicated that 6 (86%) of the 7 accelerometry-derived measures of real-world physical behavior were not significantly correlated with Functional Assessment of Cancer Therapy-General total well-being or linked Patient-Reported Outcomes Measurement Information System-Physical Function scores (Ps≥.08). In contrast, all but one of the physical behavior measures were significantly correlated with submaximal VO2 (Ps≤.03). Comparing these associations using likelihood ratio tests, we found that step counts, time in stepping bouts over 1 minute, and time in moderate to vigorous activity were more strongly associated with submaximal VO2 than with self-reported well-being or physical function (Ps≤.03). In contrast, cadence in stepping bouts over 1 minute and peak 30-second cadence were not more associated with submaximal VO2 than with the self-reported measures (Ps≥.08). CONCLUSIONS In a sample of disease-free cancer survivors, we found that several measures of real-world physical behavior were more associated with aerobic fitness than with self-reported well-being and physical function. These results highlight the possibility that in individuals who have completed cancer treatment, measures of real-world physical behavior may provide additional information compared with self-reported and performance measures. To advance the appropriate use of digital measures in oncology clinical research, further research evaluating the clinical utility of real-world physical behavior over time in large, representative samples of cancer survivors is warranted. CLINICALTRIAL ClinicalTrials.gov NCT03781154; https://clinicaltrials.gov/ct2/show/NCT03781154

Background: Digital technologies are transforming the health care system. A large part of information is generated as real-world data (RWD). Data from electronic health records and digital biomarkers have the potential to reveal associations between the benefits and adverse events of medicines, establish new patient-stratification principles, expose unknown disease correlations, and inform on preventive measures. The impact for health care payers and providers, the biopharmaceutical industry, and governments is massive in terms of health outcomes, quality of care, and cost. However, a framework to assess the preliminary quality of RWD is missing, thus hindering the conduct of population-based observational studies to support regulatory decision-making and real-world evidence. Objective: To address the need to qualify RWD, we aimed to build a web application as a tool to translate characterization of some quality parameters of RWD into a metric and propose a standard framework for evaluating the quality of the RWD. Methods: The RWD-Cockpit systematically scores data sets based on proposed quality metrics and customizable variables chosen by the user. Sleep RWD generated de novo and publicly available data sets were used to validate the usability and applicability of the web application. The RWD quality score is based on the evaluation of 7 variables: manageability specifies access and publication status; complexity defines univariate, multivariate, and longitudinal data; sample size indicates the size of the sample or samples; privacy and liability stipulates privacy rules; accessibility specifies how the data set can be accessed and to what granularity; periodicity specifies how often the data set is updated; and standardization specifies whether the data set adheres to any specific technical or metadata standard. These variables are associated with several descriptors that define specific characteristics of the data set. Results: To address the need to qualify RWD, we built the RWD-Cockpit web application, which proposes a framework and applies a common standard for a preliminary evaluation of RWD quality across data sets—molecular, phenotypical, and social—and proposes a standard that can be further personalized by the community retaining an internal standard. Applied to 2 different case studies—de novo–generated sleep data and publicly available data sets—the RWD-Cockpit could identify and provide researchers with variables that might increase quality. Conclusions: The results from the application of the framework of RWD metrics implemented in the RWD-Cockpit application suggests that multiple data sets can be preliminarily evaluated in terms of quality using the proposed metrics. The output scores—quality identifiers—provide a first quality assessment for the use of RWD. Although extensive challenges remain to be addressed to set RWD quality standards, our proposal can serve as an initial blueprint for community efforts in the characterization of RWD quality for regulated settings.

The ability to objectively measure aspects of performance and behavior is a fundamental pillar of digital health, enabling digital wellness products, decentralized trial concepts, evidence generation, digital therapeutics, and more. Emerging multimodal technologies capable of measuring several modalities simultaneously and efforts to integrate inputs across several sources are further expanding the limits of what digital measures can assess. Experts from the field of digital health were convened as part of a multi-stakeholder workshop to examine the progress of multimodal digital measures in two key areas: detection of disease and the measurement of meaningful aspects of health relevant to the quality of life. Here we present a meeting report, summarizing key discussion points, relevant literature, and finally a vision for the immediate future, including how multimodal measures can provide value to stakeholders across drug development and care delivery, as well as three key areas where headway will need to be made if we are to continue to build on the encouraging progress so far: collaboration and data sharing, removal of barriers to data integration, and alignment around robust modular evaluation of new measurement capabilities.

Background: In 2017, an estimated 17.3 million adults in the United States experienced at least one major depressive episode, with 35% of them not receiving any treatment. Underdiagnosis of depression has been attributed to many reasons, including stigma surrounding mental health, limited access to medical care, and barriers due to cost. Objective: This study aimed to determine if low-burden personal health solutions, leveraging person-generated health data (PGHD), could represent a possible way to increase engagement and improve outcomes. Methods: Here, we present the development of PSYCHE-D (Prediction of Severity Change-Depression), a predictive model developed using PGHD from more than 4000 individuals, which forecasts the long-term increase in depression severity. PSYCHE-D uses a 2-phase approach. The first phase supplements self-reports with intermediate generated labels, and the second phase predicts changing status over a 3-month period, up to 2 months in advance. The 2 phases are implemented as a single pipeline in order to eliminate data leakage and ensure results are generalizable. Results: PSYCHE-D is composed of 2 Light Gradient Boosting Machine (LightGBM) algorithm–based classifiers that use a range of PGHD input features, including objective activity and sleep, self-reported changes in lifestyle and medication, and generated intermediate observations of depression status. The approach generalizes to previously unseen participants to detect an increase in depression severity over a 3-month interval, with a sensitivity of 55.4% and a specificity of 65.3%, nearly tripling sensitivity while maintaining specificity when compared with a random model. Conclusions: These results demonstrate that low-burden PGHD can be the basis of accurate and timely warnings that an individual’s mental health may be deteriorating. We hope this work will serve as a basis for improved engagement and treatment of individuals experiencing depression.

UNSTRUCTURED Data integration, the processes by which data is aggregated, interpreted, combined, and made available for use, has been key to the development and growth of many technological solutions. In health care, we are experiencing a revolution in the use of sensors to collect data on patient behaviors and experiences. Yet, the potential of these data to transform health outcomes has been limited to date. Deficits in standards, use of different terminology, different metric systems, data rights, permissioning, privacy, and security have been well documented as challenges to digital innovation. However, the cultural adoption of sensor data integration as a priority for large-scale deployment and impact on patient lives has yet to be examined. In this paper, we take an in-depth look at case studies of sensor data integration into health data platforms for clinical research and patient care to advance key considerations in order to achieve the promise of digital health to improve clinical research and patient care at scale. These considerations are designed to support optimized, holistic (i.e. anchored in value for end consumers and patients) decision making and enable more effective sensor data integration by increasing accessibility, reliability, and trustworthiness to multiple users. We share intermediate insights from our multi-stakeholder project focused on putting forward an early framework and toolkit for sensor data integration and enable more situational awareness, thereby ensuring the future success of healthcare data integration as a whole.

UNSTRUCTURED The ability to objectively measure aspects of performance and behavior is a fundamental pillar of digital health, enabling digital wellness products, decentralized trial concepts, evidence generation, digital therapeutics, and more. Emerging multimodal technologies capable of measuring several modalities simultaneously and efforts to integrate inputs across several sources are further expanding the limits of what digital measures can assess. Experts from the field of digital health were convened as part of a multi-stakeholder workshop to examine the progress of multimodal digital measures in two key areas: detection of disease and the measurement of meaningful aspects of health relevant to the quality of life. Here we present a meeting report, summarizing key discussion points, relevant literature, and finally a vision for the immediate future, including how multimodal measures can provide value to stakeholders across drug development and care delivery, as well as three key areas where headway will need to be made if we are to continue to build on the encouraging progress so far: collaboration and data sharing, removal of barriers to data integration, and alignment around robust modular evaluation of new measurement capabilities.

Data integration, the processes by which data are aggregated, combined, and made available for use, has been key to the development and growth of many technological solutions. In health care, we are experiencing a revolution in the use of sensors to collect data on patient behaviors and experiences. Yet, the potential of this data to transform health outcomes is being held back. Deficits in standards, lexicons, data rights, permissioning, and security have been well documented, less so the cultural adoption of sensor data integration as a priority for large-scale deployment and impact on patient lives. The use and reuse of trustworthy data to make better and faster decisions across drug development and care delivery will require an understanding of all stakeholder needs and best practices to ensure these needs are met. The Digital Medicine Society is launching a new multistakeholder Sensor Data Integration Tour of Duty to address these challenges and more, providing a clear direction on how sensor data can fulfill its potential to enhance patient lives.