Supplementary Material for: A Pivotal Study to Validate the Performance of a Novel Wearable Sensor and System for Biometric Monitoring in Clinical and Remote Environments

<b><i>Background:</i></b> Increasingly, drug and device clinical trials are tracking activity levels and other quality of life indices as endpoints for therapeutic efficacy. Trials have traditionally required intermittent subject visits to the clinic that are artificial, activity-intensive, and infrequent, making trend and event detection between visits difficult. Thus, there is an unmet need for wearable sensors that produce clinical quality and medical grade physiological data from subjects in the home. The current study was designed to validate the BioStamp nPoint® system (MC10 Inc., Lexington, MA, USA), a new technology designed to meet this need. <b><i>Objective:</i></b> To evaluate the accuracy, performance, and ease of use of an end-to-end system called the BioStamp nPoint. The system consists of an investigator portal for design of trials and data review, conformal, low-profile, wearable biosensors that adhere to the skin, a companion technology for wireless data transfer to a proprietary cloud, and algorithms for analyzing physiological, biometric, and contextual data for clinical research. <b><i>Methods:</i></b> A prospective, nonrandomized clinical trial was conducted on 30 healthy adult volunteers over the course of two continuous days and nights. Supervised and unsupervised study activities enabled performance validation in clinical and remote (simulated “at home”) environments. System outputs for heart rate (HR), heart rate variability (HRV) (including root mean square of successive differences [RMSSD] and low frequency/high frequency ratio), activity classification during prescribed activities (lying, sitting, standing, walking, stationary biking, and sleep), step count during walking, posture characterization, and sleep metrics including onset/wake times, sleep duration, and respiration rate (RR) during sleep were evaluated. Outputs were compared to FDA-cleared comparator devices for HR, HRV, and RR and to ground truth investigator observations for activity and posture classifications, step count, and sleep events. <b><i>Results:</i></b> Thirty participants (77% male, 23% female; mean age 35.9 ± 10.1 years; mean BMI 28.1 ± 3.6) were enrolled in the study. The BioStamp nPoint system accurately measured HR and HRV (correlations: HR = 0.957, HRV RMSSD = 0.965, HRV ratio = 0.861) when compared to Actiheart^TM. The system accurately monitored RR (mean absolute error [MAE] = 1.3 breaths/min) during sleep when compared to a Capnostream35^TM end-tidal CO₂ monitor. When compared with investigator observations, the system correctly classified activities and posture (agreement = 98.7 and 92.9%, respectively), step count (MAE = 14.7, &lt; 3% of actual steps during a 6-min walk), and sleep events (MAE: sleep onset = 6.8 min, wake = 11.5 min, sleep duration = 13.7 min) with high accuracy. Participants indicated “good” to “excellent” usability (average System Usability Scale score of 81.3) and preferred the BioStamp nPoint system over both the Actiheart (86%) and Capnostream (97%) devices. <b><i>Conclusions:</i></b> The present study validated the BioStamp nPoint system’s performance and ease of use compared to FDA-cleared comparator devices in both the clinic and remote (home) environments.

**背景：** 如今，药物与器械临床试验愈发倾向于将活动水平及其他生活质量指标作为治疗有效性的终点评估指标。传统临床试验要求受试者间歇性前往诊所，此类就诊方式人为性强、活动负荷大且频次稀疏，导致两次就诊间的趋势与事件检测难度陡增。因此，当前亟需能够在受试者居家场景下采集临床级、医用级生理数据的可穿戴传感器。本研究旨在验证BioStamp nPoint®系统（美国马萨诸塞州列克星敦市MC10 Inc.出品）——一款专为满足该需求开发的新型技术——的性能。
**目的：** 评估名为BioStamp nPoint的端到端系统的准确性、性能与易用性。该系统包含用于临床试验设计与数据审阅的研究者门户、可贴合皮肤的薄型可穿戴生物传感器、用于将数据无线传输至专有云的配套技术，以及用于分析临床研究所需生理、生物特征与情境数据的算法。
**方法：** 本研究针对30名健康成年志愿者开展了一项为期连续两日两夜的前瞻性非随机临床试验。通过设置受控与非受控的研究活动，分别在临床环境与模拟“居家”的远程环境中完成性能验证。本研究评估了该系统的多项输出指标：心率（heart rate, HR）、心率变异性（heart rate variability, HRV，包括连续差值均方根（root mean square of successive differences, RMSSD）与低频/高频比值）、规定活动（躺卧、坐姿、站立、行走、固定式骑行与睡眠）中的活动分类、行走时的步数、姿势识别，以及睡眠指标（包括入睡/觉醒时间、睡眠时长与睡眠期间的呼吸频率（respiration rate, RR））。将系统输出与经美国食品药品监督管理局（Food and Drug Administration, FDA）批准的对照设备的HR、HRV及RR结果进行比对，并以研究者的金标准（ground truth）观测结果作为参照，评估活动与姿势分类、步数计数及睡眠事件的准确性。
**结果：** 本研究共招募30名受试者（男性占比77%，女性占比23%；平均年龄35.9±10.1岁；平均身体质量指数28.1±3.6）。与Actiheart™设备相比，BioStamp nPoint®系统对HR与HRV的测量准确性优异（相关系数：HR=0.957，HRV RMSSD=0.965，HRV比值=0.861）。与Capnostream35™呼末二氧化碳（CO₂）监测仪相比，该系统在睡眠期间对RR的监测准确性良好（平均绝对误差（mean absolute error, MAE）=1.3次/分钟）。与研究者的金标准观测结果相比，该系统对活动与姿势的分类准确率分别达98.7%与92.9%，步数计数的平均绝对误差为14.7（6分钟步行测试中实际步数的占比<3%），睡眠事件的平均绝对误差为：入睡时间6.8分钟、觉醒时间11.5分钟、睡眠时长13.7分钟，整体准确性优异。受试者评价该系统的可用性为“良好”至“极佳”（系统可用性量表（System Usability Scale）平均得分为81.3），且相较于Actiheart（86%的受试者选择）与Capnostream（97%的受试者选择）设备，更偏好使用BioStamp nPoint®系统。
**结论：** 本研究验证了BioStamp nPoint®系统在临床与远程（居家）环境中，相较于经FDA批准的对照设备的性能与易用性。