Digital Biomarkers最新文献

{"title":"Interpretation of Change in Novel Digital Measures: A Statistical Review and Tutorial.","authors":"Andrew Trigg, Bohdana Ratitch, Frank Kruesmann, Madhurima Majumder, Andrejus Parfionovas, Ulrike Krahn","doi":"10.1159/000543899","DOIUrl":"10.1159/000543899","url":null,"abstract":"<p><strong>Background: </strong>Novel clinical measures assessed by a digital health technology tool require thresholds to interpret change over time, such as the minimal clinically important difference. Establishing such thresholds is a key component of clinical validation, facilitating understanding of relevant treatment effects.</p><p><strong>Summary: </strong>Many of the approaches to derive interpretative thresholds for patient-reported outcomes can be applied to digital clinical measures. We present theoretical background to the use of interpretative thresholds, including the distinction between thresholds based on perceived importance versus measurement error, and thresholds for group- versus individual-level interpretations. We then review methods to estimate such thresholds, including anchor-based approaches. We illustrate the methods using data on cough frequency counts as measured by a wearable device in a clinical trial.</p><p><strong>Key messages: </strong>This paper provides an overview of statistical methodologies to estimate thresholds for the interpretation of change.</p>","PeriodicalId":11242,"journal":{"name":"Digital Biomarkers","volume":"9 1","pages":"52-66"},"PeriodicalIF":0.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11919315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656295","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":"Analysis Method of Real-World Digital Biomarkers for Clinical Impact in Cancer Patients.","authors":"Ingrid Oakley-Girvan, Yaya Zhai, Reem Yunis, Raymond Liu, Sharon W Davis, Ai Kubo, Sara Aghaee, Jennifer M Blankenship, Kate Lyden, Elad Neeman","doi":"10.1159/000543898","DOIUrl":"https://doi.org/10.1159/000543898","url":null,"abstract":"<p><strong>Introduction: </strong>Wearable technologies can enhance measurements completed from home by participants in decentralized clinical trials. These measurements have shown promise in monitoring patient wellness outside the clinical setting. However, there are challenges in handling data and its interpretation when using consumer wearables, requiring input from statisticians and data scientists. This article describes three methods to estimate daily steps to address gaps in data from the Apple Watch in cancer patients and uses one of these methods in an analysis of the association between daily step count estimates and clinical events for these patients.</p><p><strong>Methods: </strong>A cohort of 50 cancer patients used the DigiBioMarC app integrated with an Apple Watch for 28 days. We identified different gap types in watch data based on their length and context to estimate daily steps. Cox proportional hazards regression models were used to determine the association between step count and time to death or time to first clinical event. Decision tree modeling and participant clustering were also employed to identify digital biomarkers of physical activity that were predictive of clinical event occurrence and hazard ratio to clinical events, respectively.</p><p><strong>Results: </strong>Among the three methods explored to address missing steps, the method that identified different step data gap types according to their duration and context yielded the most reasonable estimate of daily steps. Ten hours of waking time was used to differentiate between sufficient and insufficient measurement days. Daily step count on sufficient days was the most promising predictor of time to first clinical event (<i>p</i> = 0.068). This finding was consistent with participant clustering and decision tree analyses, where the participant clusters emerged naturally based on different levels of daily steps, and the group with the highest steps on sufficient days had the lowest hazard probability of mortality and clinical events. Additionally, daily steps on sufficient days can also be used as a predictor of whether a participant will have clinical events with an accuracy of 83.3%.</p><p><strong>Conclusion: </strong>We have developed an effective way to estimate daily steps of consumer wearable data containing unknown data gaps. Daily step counts on days with sufficient sampling are a strong predictor of the timing and occurrence of clinical events, with individuals exhibiting higher daily step counts having reduced hazard of death or clinical events.</p>","PeriodicalId":11242,"journal":{"name":"Digital Biomarkers","volume":"9 1","pages":"40-51"},"PeriodicalIF":0.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647305","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":"A Holistic Approach to the Measurement of Physical Function in Clinical Research.","authors":"Jennifer C Richards, Shelby L Bachman, Krista Leonard-Corzo, Suvekshya Aryal, Jennifer M Blankenship, Ieuan Clay, Kate Lyden","doi":"10.1159/000542364","DOIUrl":"https://doi.org/10.1159/000542364","url":null,"abstract":"<p><strong>Background: </strong>This commentary highlights the evolution of our understanding of physical function (PF) and key models/frameworks that have contributed to the current holistic understanding of PF, which encompasses not only a person's performance but also the environment and any adaptations an individual utilizes. This commentary also addresses how digital health tools can facilitate and complement the assessment of holistic PF and enable both objective and subjective input from the participant in their real-world environment. Lastly, we discuss how successful implementation of digital tools within clinical research requires patient input.</p><p><strong>Summary: </strong>This commentary highlights how our understanding of PF has evolved to be more holistic.</p><p><strong>Key messages: </strong>Inclusion of digital tools within clinical research can provide a path forward to holistically assess PF in a patient-focused manner.</p>","PeriodicalId":11242,"journal":{"name":"Digital Biomarkers","volume":"9 1","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11698515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930879","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":"Multiscale Analysis of Alzheimer's Disease Using Feature Fusion in Cognitive and Sensory Brain Regions.","authors":"Aya Hassouneh, Alessander Danna-Dos-Santos, Bradley Bazuin, Saad Shebrain, Ikhlas Abdel-Qader","doi":"10.1159/000543165","DOIUrl":"10.1159/000543165","url":null,"abstract":"<p><strong>Introduction: </strong>This research is focused on early detection of Alzheimer's disease (AD) using a multiscale feature fusion framework, combining biomarkers from memory, vision, and speech regions extracted from magnetic resonance imaging and positron emission tomography images.</p><p><strong>Methods: </strong>Using 2D gray level co-occurrence matrix (2D-GLCM) texture features, volume, standardized uptake value ratios (SUVR), and obesity from different neuroimaging modalities, the study applies various classifiers, demonstrating a feature importance analysis in each region of interest. The research employs four classifiers, namely linear support vector machine, linear discriminant analysis, logistic regression (LR), and logistic regression with stochastic gradient descent (LRSGD) classifiers, to determine feature importance, leading to subsequent validation using a probabilistic neural network classifier.</p><p><strong>Results: </strong>The research highlights the critical role of brain texture features, particularly in memory regions, for AD detection. Significant sex-specific differences are observed, with males showing significance in texture features in memory regions, volume in vision regions, and SUVR in speech regions, while females exhibit significance in texture features in memory and speech regions, and SUVR in vision regions. Additionally, the study analyzes how obesity affects features used in AD prediction models, clarifying its effects on speech and vision regions, particularly brain volume.</p><p><strong>Conclusion: </strong>The findings contribute valuable insights into the effectiveness of feature fusion, sex-specific differences, and the impact of obesity on AD-related biomarkers, paving the way for future research in early AD detection strategies and cognitive impairment classification.</p>","PeriodicalId":11242,"journal":{"name":"Digital Biomarkers","volume":"9 1","pages":"23-39"},"PeriodicalIF":0.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051705","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":"Multicenter Evaluation of Machine-Learning Continuous Pulse Rate Algorithm on Wrist-Worn Device.","authors":"Weixuan Chen, Rafael Cordero, Jessie Lever Taylor, Domenico R Pangallo, Rosalind W Picard, Marisa Cruz, Giulia Regalia","doi":"10.1159/000542615","DOIUrl":"10.1159/000542615","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Though wrist-worn photoplethysmography (PPG) sensors play an important role in long-term and continuous heart rhythm monitoring, signals measured at the wrist are contaminated by more intense motion artifacts compared to other body locations. Machine learning (ML)-based algorithms can improve long-term pulse rate (PR) tracking but are associated with more stringent regulatory requirements when intended for clinical use. This study aimed to evaluate the accuracy of a digital health technology using wrist-worn PPG sensors and an ML-based algorithm to measure PR continuously.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Volunteers were enrolled in three independent clinical trials and concurrently monitored with the investigational device and FDA-cleared electrocardiography (ECG) devices during supervised protocols representative of real-life activities. The primary acceptance threshold was an accuracy root-mean-square (ARMS) ≤3 beats per minute (bpm) or 5 bpm under no-motion and motion conditions, respectively. Bias, mean absolute error (MAE), mean absolute percentage error (MAPE), limits of agreement (LoA), and Pearson and Lin's concordance correlation coefficients (⍴ and CCC) were also computed. Subgroup and outlier analyses were conducted to examine the effect of site, skin tone, age, sex, body mass index (BMI), and health status on PR accuracy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Collectively, 16,915 paired observations between the device and the reference ECG were analyzed from 157 subjects (male: 49.04%, age mean: 43 years, age range: 19-83 years, BMI mean: 26.4, BMI range: 17.5-52, Fitzpatrick class V-IV: 22.9%, cardiovascular condition: 24%). The PR output attained an accuracy of 1.67 bpm under no-motion (&lt;i&gt;n&lt;/i&gt; = 5,621 min) and 4.39 bpm under motion (&lt;i&gt;n&lt;/i&gt; = 11,294 min), satisfying the acceptance thresholds. Bias and LoA (lower, upper LoA) were -0.09 (-3.36, 3.17) bpm under no-motion and 0.51 (-8.05, 9.06) bpm under motion. MAE was 0.6 bpm in no-motion and 1.77 bpm in motion, and MAPE was 0.86% in no-motion and 2.05% in motion, with ⍴ and CCC &gt;0.98 in both conditions. ARMS values met the clinical acceptance threshold in all relevant subgroups at each clinical site separately, excluding male subjects under motion conditions (ARMS = 5.41 bpm), with more frequent and larger outliers due to stronger forearm contractions. However, these mostly occurred in isolation and, therefore would not impact the clinical utility or usability of the device for its intended use of retrospective review and trend analysis (⍴ and CCC &gt;0.97 and MAPE = 2.61%).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The analytical validation conducted in this study demonstrated clinical-grade accuracy and generalizability of ML-based continuous PR estimations across a full range of physical motions, health conditions, and demographic variables known to confound PPG signals, paving the way for device usage by populations most likely to benefit from continuous PR m","PeriodicalId":11242,"journal":{"name":"Digital Biomarkers","volume":"8 1","pages":"218-228"},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11637493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817627","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 Wrist-Worn Accelerometer-Based Step-Count Methods during Structured and Free-Living Activities.","authors":"Robert T Marcotte, Shelby L Bachman, Yaya Zhai, Ieuan Clay, Kate Lyden","doi":"10.1159/000542850","DOIUrl":"10.1159/000542850","url":null,"abstract":"<p><strong>Introduction: </strong>Wrist-worn accelerometers can capture stepping behavior passively, continuously, and remotely. Methods utilizing peak detection, threshold crossing, and frequency analysis have been used to detect steps from wrist-worn accelerometer data, but it remains unclear how different approaches perform across a range of walking speeds and free-living activities. In this study, we evaluated the performance of four open-source methods for deriving step counts from wrist-worn accelerometry data, when applied to data from a range of structured locomotion and free-living activities. In addition, we assessed how modifying the parameters of these methods would affect their performance.</p><p><strong>Methods: </strong>Twenty-one participants (ages 20-33) wore an ActiGraph CentrePoint Insight Watch (Actigraph, LLC) on their non-dominant wrist while completing structured locomotion activities in a motion capture laboratory and during a free-living period in a mock apartment. Criterion step counts were determined from motion capture heel-strike events and from StepWatch 3 (Modus Health, LLC) during the free-living period. Four open-source methods implementing different algorithmic approaches were applied to CPIW data to derive step counts. The quantity and timing of method-derived and criterion steps during each type of activity were then compared.</p><p><strong>Results: </strong>In terms of performance during structured locomotion, methods that relied on a single parameter, such as peak detection or threshold crossing, demonstrated the lowest bias among those investigated. Furthermore, three of the four investigated methods overestimated step counts during slow walking and underestimated step counts during fast walking, while the last method consistently underestimated at least half of the recorded steps across all speeds. During free-living activities, the method relying on frequency analysis exhibited the lowest percent error of all methods. Finally, we found that the incorporation of a locomotion classifier, wherein steps were only estimated during identified locomotion periods, reduced error for two methods when applied to data across structured and free-living settings.</p><p><strong>Conclusion: </strong>In studying the performance of different step-counting approaches across different settings, we found a tradeoff between performance during structured walking and that during free-living activities. These findings highlight the opportunity for novel, context-aware methods for accurate step counting across real-world settings.</p>","PeriodicalId":11242,"journal":{"name":"Digital Biomarkers","volume":"9 1","pages":"10-22"},"PeriodicalIF":0.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051703","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":"The State of Digital Biomarkers in Mental Health.","authors":"Ellen W McGinnis, Josh Cherian, Ryan S McGinnis","doi":"10.1159/000542320","DOIUrl":"10.1159/000542320","url":null,"abstract":"","PeriodicalId":11242,"journal":{"name":"Digital Biomarkers","volume":"8 1","pages":"210-217"},"PeriodicalIF":0.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11584197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709413","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":"The Imperative of Voice Data Collection in Clinical Trials.","authors":"Guy Fagherazzi, Yaël Bensoussan","doi":"10.1159/000541456","DOIUrl":"10.1159/000541456","url":null,"abstract":"","PeriodicalId":11242,"journal":{"name":"Digital Biomarkers","volume":"8 1","pages":"207-209"},"PeriodicalIF":0.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616559","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":"eHealth and mHealth in Antimicrobial Stewardship Programs.","authors":"Felipe Francisco Tuon, Tiago Zequinao, Marcelo Silva da Silva, Kleber Oliveira Silva","doi":"10.1159/000541120","DOIUrl":"https://doi.org/10.1159/000541120","url":null,"abstract":"<p><strong>Background: </strong>The global need for rapid diagnostic methods for pathogen identification and antimicrobial susceptibility testing (AST) is underscored by the increasing bacterial resistance and limited therapeutic options, especially critical in sepsis management.</p><p><strong>Summary: </strong>This review examines the aspects of the eHealth and mHealth in Antimicrobial Stewardship Programs (ASPs) to improve the treatment of infections and rational use of antimicrobials.</p><p><strong>Key messages: </strong>The evolution from traditional phenotype-based methods to rapid molecular and mass spectrometry techniques has significantly decreased result turnaround times, improving patient outcomes. Despite advancements, the complex decision-making in antimicrobial therapy often exceeds the capacity of many clinicians, highlighting the importance of ASPs. These programs, integrating mHealth and eHealth, leverage technology to enhance healthcare services and patient outcomes, particularly in remote or resource-limited settings. However, the application of such technologies in antimicrobial management remains underexplored in hospitals. The development of platforms combining antimicrobial prescription data with pharmacotherapeutic algorithms and laboratory integration can significantly reduce costs and improve hospitalization times and mortality rates.</p>","PeriodicalId":11242,"journal":{"name":"Digital Biomarkers","volume":"8 1","pages":"194-206"},"PeriodicalIF":0.0,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11521536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544332","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":"Detecting Longitudinal Trends between Passively Collected Phone Use and Anxiety among College Students.","authors":"Joseph A Gyorda, Damien Lekkas, Nicholas C Jacobson","doi":"10.1159/000540546","DOIUrl":"10.1159/000540546","url":null,"abstract":"<p><strong>Introduction: </strong>Existing theories and empirical works link phone use with anxiety; however, most leverage subjective self-reports of phone use (e.g., validated questionnaires) that may not correspond well with true behavior. Moreover, most works linking phone use with anxiety do not interrogate associations within a temporal framework. Accordingly, the present study sought to investigate the utility of passively sensed phone use as a longitudinal predictor of anxiety symptomatology within a population particularly vulnerable to experiencing anxiety.</p><p><strong>Methods: </strong>Using data from the GLOBEM study, which continuously collected longitudinal behavioral data from a college cohort of <i>N</i> = 330 students, weekly PHQ-4 anxiety subscale scores across 3 years (2019-2021) were paired with median daily phone use records from the 2 weeks prior to anxiety self-report completion. Phone use was operationalized through unlock duration which was passively curated via Apple's \"Screen Time\" feature. GPS-tracked location data was further utilized to specify whether an individual's phone use was at home or away from home. Within-individual and temporal associations between phone use and anxiety were modeled within an ordinal mixed-effects logistic regression framework.</p><p><strong>Results: </strong>While there was no significant association between anxiety levels and either median total phone use or median phone use at home, participants in the top quartile of median phone use away from home were predicted to exhibit clinically significant anxiety levels 20% more frequently than participants in the bottom quartile during the first study year; however, this association weakened across successive years. Importantly, these associations remained after controlling for age, physical activity, sleep, and baseline anxiety levels and were not recapitulated when operationalizing phone use with unlock frequency.</p><p><strong>Conclusions: </strong>These findings suggest that phone use may be leveraged as a means of mitigating or coping with anxiety in social situations outside the home, while pandemic-related developments may also have attenuated this behavior later in the study. Nevertheless, the present results suggest promise in interrogating a larger suite of objectively measured phone use behaviors within the context of social anxiety.</p>","PeriodicalId":11242,"journal":{"name":"Digital Biomarkers","volume":"8 1","pages":"181-193"},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11521436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544330","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}