Digital Biomarkers最新文献

{"title":"Automated Real-World Video Analysis of Sit-to-Stand Transitions Predicts Parkinson's Disease Severity.","authors":"Catherine Morgan, Alessandro Masullo, Majid Mirmehdi, Hanna Kristiina Isotalus, Ferdian Jovan, Ryan McConville, Emma L Tonkin, Alan Whone, Ian Craddock","doi":"10.1159/000530953","DOIUrl":"10.1159/000530953","url":null,"abstract":"<p><strong>Introduction: </strong>Technology holds the potential to track disease progression and response to neuroprotective therapies in Parkinson's disease (PD). The sit-to-stand (STS) transition is a frequently occurring event which is important to people with PD. The aim of this study was to demonstrate an automatic approach to quantify STS duration and speed using a real-world free-living dataset and look at clinical correlations of the outcomes, including whether STS parameters change when someone withholds PD medications.</p><p><strong>Methods: </strong>Eighty-five hours of video data were collected from 24 participants staying in pairs for 5-day periods in a naturalistic setting. Skeleton joints were extracted from the video data; the head trajectory was estimated and used to estimate the STS parameters of duration and speed.</p><p><strong>Results: </strong>3.14 STS transitions were seen per hour per person on average. Significant correlations were seen between automatic and manual STS duration (Pearson rho - 0.419, <i>p</i> = 0.042) and between automatic STS speed and manual STS duration (Pearson rho - 0.780, <i>p</i> < 0.001). Significant and strong correlations were seen between the gold-standard clinical rating scale scores and both STS duration and STS speed; these correlations were not seen in the STS transitions when the participants were carrying something in their hand(s). Significant differences were seen at the cohort level between control and PD participants' ON medications' STS duration (U = 6,263, <i>p</i> = 0.018) and speed (U = 9,965, <i>p</i> < 0.001). At an individual level, only two participants with PD became significantly slower to STS when they were OFF medications; withholding medications did not significantly change STS duration at an individual level in any participant.</p><p><strong>Conclusion: </strong>We demonstrate a novel approach to automatically quantify and ecologically validate two STS parameters which correlate with gold-standard clinical tools measuring disease severity in PD.</p>","PeriodicalId":11242,"journal":{"name":"Digital Biomarkers","volume":"7 1","pages":"92-103"},"PeriodicalIF":0.0,"publicationDate":"2023-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/40/91/dib-2023-0007-0001-530953.PMC10425718.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10022613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Validation of Novel Digital Measures: Statistical Methods for Reliability Evaluation.","authors":"Bohdana Ratitch, Andrew Trigg, Madhurima Majumder, Vanja Vlajnic, Nicole Rethemeier, Richard Nkulikiyinka","doi":"10.1159/000531054","DOIUrl":"10.1159/000531054","url":null,"abstract":"<p><strong>Background: </strong>Assessment of reliability is one of the key components of the validation process designed to demonstrate that a novel clinical measure assessed by a digital health technology tool is fit-for-purpose in clinical research, care, and decision-making. Reliability assessment contributes to characterization of the signal-to-noise ratio and measurement error and is the first indicator of potential usefulness of the proposed clinical measure.</p><p><strong>Summary: </strong>Methodologies for reliability analyses are scattered across literature on validation of PROs, wet biomarkers, etc., yet are equally useful for digital clinical measures. We review a general modeling framework and statistical metrics typically used for reliability assessments as part of the clinical validation. We also present methods for the assessment of agreement and measurement error, alongside modified approaches for categorical measures. We illustrate the discussed techniques using physical activity data from a wearable device with an accelerometer sensor collected in clinical trial participants.</p><p><strong>Key messages: </strong>This paper provides statisticians and data scientists, involved in development and validation of novel digital clinical measures, an overview of the statistical methodologies and analytical tools for reliability assessment.</p>","PeriodicalId":11242,"journal":{"name":"Digital Biomarkers","volume":"7 1","pages":"74-91"},"PeriodicalIF":0.0,"publicationDate":"2023-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/90/b8/dib-2023-0007-0001-531054.PMC10425717.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10017660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Assessment of an Artificial Intelligence-Based Tool for Ptosis Measurement in Adult Myasthenia Gravis Patients Using Selfie Video Clips Recorded on Smartphones.","authors":"Meelis Lootus, Lulu Beatson, Lucas Atwood, Theo Bourdais, Sandra Steyaert, Chethan Sarabu, Zeenia Framroze, Harriet Dickinson, Jean-Christophe Steels, Emily Lewis, Nirav R Shah, Francesca Rinaldo","doi":"10.1159/000531224","DOIUrl":"10.1159/000531224","url":null,"abstract":"<p><strong>Introduction: </strong>Myasthenia gravis (MG) is a rare autoimmune disease characterized by muscle weakness and fatigue. Ptosis (eyelid drooping) occurs due to fatigue of the muscles for eyelid elevation and is one symptom widely used by patients and healthcare providers to track progression of the disease. Margin reflex distance 1 (MRD1) is an accepted clinical measure of ptosis and is typically assessed using a hand-held ruler. In this work, we develop an AI model that enables automated measurement of MRD1 in self-recorded video clips collected using patient smartphones.</p><p><strong>Methods: </strong>A 3-month prospective observational study collected a dataset of video clips from patients with MG. Study participants were asked to perform an eyelid fatigability exercise to elicit ptosis while filming \"selfie\" videos on their smartphones. These images were collected in nonclinical settings, with no in-person training. The dataset was annotated by non-clinicians for (1) eye landmarks to establish ground truth MRD1 and (2) the quality of the video frames. The ground truth MRD1 (in millimeters, mm) was calculated from eye landmark annotations in the video frames using a standard conversion factor, the horizontal visible iris diameter of the human eye. To develop the model, we trained a neural network for eye landmark detection consisting of a ResNet50 backbone plus two dense layers of 78 dimensions on publicly available datasets. Only the ResNet50 backbone was used, discarding the last two layers. The embeddings from the ResNet50 were used as features for a support vector regressor (SVR) using a linear kernel, for regression to MRD1, in mm. The SVR was trained on data collected remotely from MG patients in the prospective study, split into training and development folds. The model's performance for MRD1 estimation was evaluated on a separate test fold from the study dataset.</p><p><strong>Results: </strong>On the full test fold (<i>N</i> = 664 images), the correlation between the ground truth and predicted MRD1 values was strong (<i>r</i> = 0.732). The mean absolute error was 0.822 mm; the mean of differences was -0.256 mm; and 95% limits of agreement (LOA) were -0.214-1.768 mm. Model performance showed no improvement when test data were gated to exclude \"poor\" quality images.</p><p><strong>Conclusions: </strong>On data generated under highly challenging real-world conditions from a variety of different smartphone devices, the model predicts MRD1 with a strong correlation (<i>r</i> = 0.732) between ground truth and predicted MRD1.</p>","PeriodicalId":11242,"journal":{"name":"Digital Biomarkers","volume":"7 1","pages":"63-73"},"PeriodicalIF":0.0,"publicationDate":"2023-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5b/23/dib-2023-0007-0001-531224.PMC10399113.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9954353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial-Temporal Analysis of Gait in Amyotrophic Lateral Sclerosis Using Foot-Worn Inertial Sensors: An Observational Study","authors":"Meghan Lukac, Hannah Luben, Anne E Martin, Zachary Simmons, A. Geronimo","doi":"10.1159/000530067","DOIUrl":"https://doi.org/10.1159/000530067","url":null,"abstract":"Introduction: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that alters gait and increases the risk of falls. The current model of care involves in-person multidisciplinary clinic visits to, in part, assess alterations in gait, evaluate safety, and make recommendations for management. Clinic visits, however, are relatively infrequent, and multidisciplinary evaluations can be physically demanding for patients. To better understand how gait changes over time in those with ALS and enable healthcare providers to properly respond to these changes, remote monitoring of functional mobility would be advantageous. Methods: The objective of this study was to remotely track long-term changes in walking speed using wearable inertial measurement units (IMUs). Nine ALS patients and 6 healthy controls submitted twice-weekly home walking recordings for 24 and 4 weeks, respectively. An IMU data processing method was developed and validated against laboratory-measured walking speed. Results: For both ALS patients and healthy controls, home walking speed was less than clinic walking speed by an average of 0.19 m/s (p = 0.0024). Over 24 weeks, home walking speed significantly decreased for 5 of 9 ALS patients at an average of −0.021 m/s/months (p = 0.005). Those who eventually transitioned to using assistive device (AD) while on the study demonstrated a greater decrease in walking speed than those who did not. Conclusions: Remote longitudinal gait monitoring of ALS patients is feasible with the use of an IMU. Decreases in walking speed were detected in the majority of patients, most strongly in those who eventually transitioned to an AD. Home walking speed may more accurately represent the walking abilities of ALS patients in their real-life environments, a finding which further supports the case for remote monitoring in ALS.","PeriodicalId":11242,"journal":{"name":"Digital Biomarkers","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139372580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pilot Study of a Wearable Hydration Monitor in Haemodialysis Patients: Haemodialysis Outcomes & Patient Empowerment Study 02.","authors":"Vicki Sandys, Lavleen Bhat, Emer O'Hare, Anna Ninan, Kevin Doyle, Shane Kelly, Peter Conlon, Donal Sexton, Colin Edwards, Paul McAleese, Conall O'Seaghdha","doi":"10.1159/000529899","DOIUrl":"10.1159/000529899","url":null,"abstract":"<p><strong>Introduction: </strong>We aimed to assess the validity and reproducibility of a wearable hydration device in a cohort of maintenance dialysis patients.</p><p><strong>Methods: </strong>We conducted a prospective, single-arm observational study on 20 haemodialysis patients between January and June 2021 in a single centre. A prototype wearable infrared spectroscopy device, termed the Sixty device, was worn on the forearm during dialysis sessions and nocturnally. Bioimpedance measurements were performed 4 times using the body composition monitor (BCM) over 3 weeks. Measurements from the Sixty device were compared with the BCM overhydration index (litres) pre- and post-dialysis and with standard haemodialysis parameters.</p><p><strong>Results: </strong>12 out of 20 patients had useable data. Mean age was 52 ± 12.4 years. The overall accuracy for predicting pre-dialysis categories of fluid status using Sixty device was 0.55 [K = 0.00; 95% CI: -0.39-0.42]. The accuracy for the prediction of post-dialysis categories of volume status was low [accuracy = 0.34, K = 0.08; 95% CI: -0.13-0.3]. Sixty outputs at the start and end of dialysis were weakly correlated with pre- and post-dialysis weights (<i>r</i> = 0.27 and <i>r</i> = 0.27, respectively), as well as weight loss during dialysis (<i>r</i> = 0.31), but not ultrafiltration volume (<i>r</i> = 0.12). There was no difference between the change in Sixty readings overnight and the change in Sixty readings during dialysis (mean difference 0.09 ± 1.5 kg), [<i>t</i>(39) = 0.38, <i>p</i> = 0.71].</p><p><strong>Conclusion: </strong>A prototype wearable infrared spectroscopy device was unable to accurately assess changes in fluid status during or between dialysis sessions. In the future, hardware development and advances in photonics may enable the tracking of interdialytic fluid status.</p>","PeriodicalId":11242,"journal":{"name":"Digital Biomarkers","volume":"7 1","pages":"18-27"},"PeriodicalIF":0.0,"publicationDate":"2023-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10184568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9841625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reverse Engineering of Digital Measures: Inviting Patients to the Conversation.","authors":"Ieuan Clay, Nele Peerenboom, Dana E Connors, Steven Bourke, Alison Keogh, Katarzyna Wac, Tova Gur-Arie, Justin Baker, Christopher Bull, Andrea Cereatti, Francesca Cormack, Damien Eggenspieler, Luca Foschini, Raluca Ganea, Peter M A Groenen, Nicole Gusset, Elena Izmailova, Christoph M Kanzler, Lada Leyens, Kate Lyden, Arne Mueller, Julian Nam, Wan-Fai Ng, David Nobbs, Foteini Orfaniotou, Thanneer Malai Perumal, Wojciech Piwko, Anja Ries, Alf Scotland, Nick Taptiklis, John Torous, Beatrix Vereijken, Shuai Xu, Laurenz Baltzer, Thorsten Vetter, Jörg Goldhahn, Steven C Hoffmann","doi":"10.1159/000530413","DOIUrl":"10.1159/000530413","url":null,"abstract":"<p><strong>Background: </strong>Digital measures offer an unparalleled opportunity to create a more holistic picture of how people who are patients behave in their real-world environments, thereby establishing a better connection between patients, caregivers, and the clinical evidence used to drive drug development and disease management. Reaching this vision will require achieving a new level of co-creation between the stakeholders who design, develop, use, and make decisions using evidence from digital measures.</p><p><strong>Summary: </strong>In September 2022, the second in a series of meetings hosted by the Swiss Federal Institute of Technology in Zürich, the Foundation for the National Institutes of Health Biomarkers Consortium, and sponsored by Wellcome Trust, entitled \"Reverse Engineering of Digital Measures,\" was held in Zurich, Switzerland, with a broad range of stakeholders sharing their experience across four case studies to examine how patient centricity is essential in shaping development and validation of digital evidence generation tools.</p><p><strong>Key messages: </strong>In this paper, we discuss progress and the remaining barriers to widespread use of digital measures for evidence generation in clinical development and care delivery. We also present key discussion points and takeaways in order to continue discourse and provide a basis for dissemination and outreach to the wider community and other stakeholders. The work presented here shows us a blueprint for how and why the patient voice can be thoughtfully integrated into digital measure development and that continued multistakeholder engagement is critical for further progress.</p>","PeriodicalId":11242,"journal":{"name":"Digital Biomarkers","volume":"7 1","pages":"28-44"},"PeriodicalIF":0.0,"publicationDate":"2023-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10189241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9852819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analytical Validation of a Webcam-Based Assessment of Speech Kinematics: Digital Biomarker Evaluation following the V3 Framework.","authors":"Leif Simmatis, Saeid Alavi Naeini, Deniz Jafari, Michael Kai Yue Xie, Chelsea Tanchip, Niyousha Taati, Scotia McKinlay, Rupinder Sran, Justin Truong, Diego L Guarin, Babak Taati, Yana Yunusova","doi":"10.1159/000529685","DOIUrl":"10.1159/000529685","url":null,"abstract":"<p><strong>Introduction: </strong>Kinematic analyses have recently revealed a strong potential to contribute to the assessment of neurological diseases. However, the validation of home-based kinematic assessments using consumer-grade video technology has yet to be performed. In line with best practices for digital biomarker development, we sought to validate webcam-based kinematic assessment against established, laboratory-based recording gold standards. We hypothesized that webcam-based kinematics would possess psychometric properties comparable to those obtained using the laboratory-based gold standards.</p><p><strong>Methods: </strong>We collected data from 21 healthy participants who repeated the phrase \"buy Bobby a puppy\" (BBP) at four different combinations of speaking rate and volume: Slow, Normal, Loud, and Fast. We recorded these samples twice back-to-back, simultaneously using (1) an electromagnetic articulography (\"EMA\"; NDI Wave) system, (2) a 3D camera (Intel RealSense), and (3) a 2D webcam for video recording via an in-house developed app. We focused on the extraction of kinematic features in this study, given their demonstrated value in detecting neurological impairments. We specifically extracted measures of speed/acceleration, range of motion (ROM), variability, and symmetry using the movements of the center of the lower lip during these tasks. Using these kinematic features, we derived measures of (1) agreement between recording methods, (2) test-retest reliability of each method, and (3) the validity of webcam recordings to capture expected changes in kinematics as a result of different speech conditions.</p><p><strong>Results: </strong>Kinematics measured using the webcam demonstrated good agreement with both the RealSense and EMA (ICC-A values often ≥0.70). Test-retest reliability, measured using the absolute agreement (2,1) formulation of the intraclass correlation coefficient (i.e., ICC-A), was often \"moderate\" to \"strong\" (i.e., ≥0.70) and similar between the webcam and EMA-based kinematic features. Finally, the webcam kinematics were typically as sensitive to differences in speech tasks as EMA and the 3D camera gold standards.</p><p><strong>Discussion and conclusions: </strong>Our results suggested that webcam recordings display good psychometric properties, comparable to laboratory-based gold standards. This work paves the way for a large-scale clinical validation to continue the development of these promising technologies for the assessment of neurological diseases via home-based methods.</p>","PeriodicalId":11242,"journal":{"name":"Digital Biomarkers","volume":"7 1","pages":"7-17"},"PeriodicalIF":0.0,"publicationDate":"2023-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10187538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9851840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feasibility of Measuring Physiological Responses to Breakthrough Infections and COVID-19 Vaccine Using a Wearable Ring Sensor.","authors":"Gerald Norman Pho, Nina Thigpen, Shyamal Patel, Hal Tily","doi":"10.1159/000528874","DOIUrl":"10.1159/000528874","url":null,"abstract":"<p><p>Continuous monitoring using commercial-grade wearable technology was used to quantify the physiological response to reported COVID-19 infections and vaccinations in five biometric measurements. Larger responses were observed following confirmed COVID-19 infection reported by unvaccinated versus vaccinated individuals. Responses following reported vaccination were smaller in both magnitude and duration compared to infection and mediated by both dose number and age. Our results suggest commercial-grade wearable technology as a potential platform on which to build screening tools for early detection of illness, including COVID-19 breakthrough cases.</p>","PeriodicalId":11242,"journal":{"name":"Digital Biomarkers","volume":"7 1","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2023-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10062187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9241869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using Clinical Scales and Digital Measures to Explore Falls in Patients with Lewy Body Dementia.","authors":"Chakib Battioui,&nbsp;Albert Man,&nbsp;Melissa Pugh,&nbsp;Jian Wang,&nbsp;Xiangnan Dang,&nbsp;Hui Zhang,&nbsp;Paul Ardayfio,&nbsp;Leanne Munsie,&nbsp;Ann Marie Hake,&nbsp;Kevin Biglan","doi":"10.1159/000529623","DOIUrl":"https://doi.org/10.1159/000529623","url":null,"abstract":"<p><strong>Introduction: </strong>PRESENCE was a phase 2 clinical trial assessing the efficacy of mevidalen, a D1 receptor positive allosteric modulator, for symptomatic treatment of Lewy body dementia (LBD). Mevidalen demonstrated improvements in motor and non-motor features of LBD, global functioning, and actigraphy-measured activity and daytime sleep. Adverse events (AEs) of fall were numerically increased in mevidalen-treated participants.</p><p><strong>Methods: </strong>A subset of PRESENCE participants wore a wrist actigraphy device for 2-week periods pre-, during, and posttreatment. Actigraphy sleep and activity measures were derived per period and analyzed to assess for their association with participants' reports of an AE of fall. Prespecified baseline and treatment-emergent clinical characteristics were also included in the retrospective analysis of falls. Independent-samples <i>t</i> test and χ² test were performed to compare the means and proportions between individuals with/without falls.</p><p><strong>Results: </strong>A trend toward more falls was observed with mevidalen treatment (31/258 mevidalen-treated vs. 4/86 in placebo-treated participants: <i>p</i> = 0.12). Higher body mass index (BMI) (<i>p</i> < 0.05), more severe disease measured by baseline Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part II (<i>p</i> < 0.05), and a trend toward improved Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog₁₃) (<i>p</i> = 0.06) were associated with individuals with falls. No statistically significant associations with falls and treatment-emergent changes were observed.</p><p><strong>Conclusion: </strong>The association of falls with worse baseline disease severity and higher BMI and overall trend toward improvements on cognitive and motor scales suggest that falls in PRESENCE may be related to increased activity in mevidalen-treated participants at greater risk for falling. Future studies to confirm this hypothesis using fall diaries and digital assessments are necessary.</p>","PeriodicalId":11242,"journal":{"name":"Digital Biomarkers","volume":"7 1","pages":"54-62"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10315006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9857804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How Much Evidence Is Enough? Research Sponsor Experiences Seeking Regulatory Acceptance of Digital Health Technology-Derived Endpoints.","authors":"Brian Perry,&nbsp;Lindsay Kehoe,&nbsp;Teresa Swezey,&nbsp;Quentin Le Masne,&nbsp;Jörg Goldhahn,&nbsp;Alicia Staley,&nbsp;Amy Corneli","doi":"10.1159/000529878","DOIUrl":"https://doi.org/10.1159/000529878","url":null,"abstract":"<p><strong>Introduction: </strong>Digital health technologies (DHTs) provide opportunities for real-time data collection and assessment of patient function. However, use of DHT-derived endpoints in clinical trials to support medical product labelling claims is limited.</p><p><strong>Methods: </strong>From November 2020 through March 2021, the Clinical Trials Transformation Initiative (CTTI) conducted a qualitative descriptive study using semi-structured interviews with sponsors of clinical trials that used DHT-derived endpoints. We aimed to learn about their experiences, including their interactions with regulators and the challenges they encountered. Using applied thematic analysis, we identified barriers to and recommendations for using DHT-derived endpoints in pivotal trials.</p><p><strong>Results: </strong>Sponsors identified five key challenges to incorporating DHT-derived endpoints in clinical trials. These included (1) a need for additional regulatory clarity specific to DHT-derived endpoints, (2) the official clinical outcome assessment qualification process being impractical for the biopharmaceutical industry, (3) a lack of comparator clinical endpoints, (4) a lack of validated DHTs and algorithms for concepts of interest, and (5) a lack of operational support from DHT vendors.</p><p><strong>Discussion/conclusion: </strong>CTTI shared the interview findings with the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) and during a multi-stakeholder expert meeting. Based on these discussions, we provide several new and revised tools to aid sponsors in using DHT-derived endpoints in pivotal trials to support labelling claims.</p>","PeriodicalId":11242,"journal":{"name":"Digital Biomarkers","volume":"7 1","pages":"45-53"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10315005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9928190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}