ID-Cap System: Next generation ingestible sensors for medication adherence measurement

摘要 不坚持药物治疗会在世界范围内导致严重的发病率和死亡率。在 美国，药物不遵守导致医疗保健每年管理成本5280亿美元 与不坚持相关的后果，包括慢性疾病的进展。用于药物治疗 艾滋病毒暴露前预防(PrEP)和抗逆转录病毒治疗(ART)等方案的发病率与 不遵守包括获得和传播艾滋病毒、机会性感染和恶化 慢性艾滋病毒相关合并症。为了了解遵守和减少不遵守，新的直接 需要确认摄入事件的依从性工具。当前间接测量检测代理 依从性指示器，如自我报告、药片计数或电子依附设备，可检测是否打开 药瓶。这些方法存在回忆偏差，往往不能完全衡量用户的忠诚度。在……里面 对比度，直接措施，如直接观察或视频观察的治疗，利用临床医生或 医护人员可以目视确认药物摄入，可以核实药物摄入事件。然而，这些 直接方法昂贵，需要人员，因此难以推广。药物的直接确认 血清或头发中的浓度可作为药物依从性的证据，但这些方法需要 专门的分析技术，并提供可能忽略次优时段的总体遵守 坚持不懈。为了应对间接和直接遵守措施的局限性，数字药丸--一种 可摄取的射频发射器和明胶胶囊，过度封装所需的药物- 代表一种工具，可以直接确认药物摄取，并创新地向 用户和关怀团队。2019年，etectRx获得了FDA 510K对ID-Cap的批准，这是一种数字避孕药系统， 直接实时测量服药依从性。通过K23DA044874和独立调查员- 由Gilead Sciences发起的研究资助，我们已经证明了使用ID-Cap的可行性 个人之间的系统，以衡量PrEP和阿片类药物的依从性。在这些调查中，我们 在患者中发现了广泛的兴趣，通过开发一种手腕可穿戴设备来优化系统 从数字药丸中收集遵守信息的阅读器。因此，第一阶段SBIR开发了下一阶段- 带手腕可穿戴读卡器的新一代ID-Cap系统。在目标1中，我们将使当前版本微型化 并进行实验室测试，以确保所有组件正常工作并从 服下的数字药片。接下来，在目标2中，我们将进行开放标签试点示范试验，以了解 下一代ID-Cap系统在使用PrEP(N=15)和ART的N=30人中的真实可用性 15例。我们的成功基准，开发微型手腕阅读器和演示 在临床试验中的可用性，将使我们处于最佳地位，推动etectRx的商业化努力 第二阶段SBIR的背景。

ABSTRACT Nonadherence to medication therapy results in significant morbidity and mortality across the world. In the United States, medication nonadherence results in $528 billion of annual costs to healthcare to manage consequences associated with nonadherence including progression of chronic disease. For medication regimens like HIV pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART), morbidity associated with nonadherence includes acquisition and transmission of HIV, opportunistic infections, and exacerbation of chronic HIV related comorbidities. In order to understand adherence and mitigate nonadherence, new direct adherence tools that confirm ingestion events are needed. Current indirect measures detect surrogate indicators of adherence like self-report, pill counting, or electronic adherence devices that detect the opening of pill bottles. These methods suffer from recall bias and often provide an incomplete measure of adherence. In contrast, direct measures, such as directly observed or video observed therapy that utilizes a clinician or healthcare worker to visually confirm medication ingestion, can verify medication ingestion events. Yet, these direct methods are expensive, require personnel, and are therefore difficult to scale. Direct confirmation of drug concentration in serum or hair may be used as evidence of medication adherence, but these methods require specialized analysis techniques and provide overall adherence which may overlook periods of suboptimal adherence. In response to the limitations of both indirect and direct measures of adherence, digital pills—an ingestible radiofrequency emitter and gelatin capsule which over encapsulates the desired medication— represent a tool that can directly confirm medication ingestions and innovatively provide feedback to both the user and care team. In 2019, etectRx received FDA 510K clearance for the ID-Cap, a digital pill system that directly measures medication adherence in real-time. Through K23DA044874 and independent investigator- initiated research grants from Gilead Sciences, we have demonstrated the feasibility of using the ID-Cap System among individuals to measure adherence to PrEP and opioids. During these investigations, we discovered widespread interest among patients in optimizing the system by developing a wrist-borne wearable Reader to collection adherence information from the digital pill. This Phase I SBIR therefore develops the next- generation ID-Cap System with a wrist-borne wearable reader. In Aim 1, we will miniaturize the current version of the Reader and conduct laboratory testing to ensure all components are functional and acquire signal from ingested digital pills. Next, in Aim 2, we will conduct an open-label pilot demonstration trial to understand the real-world usability of the next generation ID-Cap System among N=30 individuals on PrEP (N=15) and ART (N=15). Our benchmarks for success, the development of a miniaturized wrist-worn reader and demonstration of usability in a clinical trial, will optimally position us to advance commercialization efforts at etectRx in the context of a Phase II SBIR.