Leveraging Technology to Improve Medication Adherence in Adolescent and Young Adult Kidney or Liver Transplant Recipients

在接受过肾或肝移植的青少年和青壮年(AYA)中，超过三分之一的人 不遵守免疫抑制药物，这是器官排斥、移植失败和死亡的主要原因。 尽管美国移植学会呼吁采用实时方法来解决免疫抑制问题 不遵守，没有使用实时遵守数据(例如，电子地堡)来验证的指标 找出那些面临被拒绝风险的人，并且没有有效的干预措施来利用这些数据来提高遵从性。 因此，我们将通过验证新的“实时遵守”来填补不遵守管理中的这些关键空白 一种新的仪器，可以革命性地检测不遵守情况的方式，通过将 非侵入性的、易于下载的、带有时间戳的电子地堡数据，符合他克莫司的血液水平标准 偏离度(药物摄取的生物学指数)在免疫抑制剂未粘连的时刻指向 会导致拒绝。我们将及时利用这些实时的每日给药信息，以促进遵守 适应性干预(JITAI)，一种能够完全纳入AYA日常生活的尖端移动健康方法 电子监控的遵守情况，在Aya最需要的时候提供量身定制的干预内容。 目前，还没有用于这一目的的JITAI。我们将进行这项重要的研究，其中包括使用一种微型 随机试验，创造成功的JITAI的最先进的实验设计。为了发展我们的吉泰，我们 将修改有希望的现有干预措施以促进Aya遵守(已发送遵守支持消息 剂量到期时)通过仅在错过药物时触发依从性支持消息并提供 吃药时要表扬信息。这一干预的吉台版本将与阿亚肾脏或 肝移植受者参加为期12周的微型随机试验，以确定干预内容和时机 最大限度地发挥吉泰对坚守的影响。Ayas将在每一次电子监控未命中后随机进行 他克莫司剂量接收(1)依从性支持消息或(2)无消息。每次按时服药后，AYAS 将被随机地接收(1)表扬消息或(2)无消息。Ayas在吉泰的参与将是 具有支持长期吸收的定性特征。我们的发现将解决以下方面的重大知识差距 如何最佳地利用技术来有效地衡量和改善阿雅肾脏的用药依从性 或肝移植接受者，减少非依从性排斥反应、移植物丢失和死亡，并改善人们的 健康和生活质量。伊顿博士的学习和培训活动将为她使用先进的方法做好准备 验证新的临床指标，设计JITAI，进行微随机试验，并改善移动健康 订婚。对于伊顿博士来说，获得K23的支持是至关重要的，以获得创新的 方法和实现她重要的科学目标。伊顿博士的职业发展活动将在 约翰斯·霍普金斯。这项研究的结果将为伊顿博士的R01支持的完全 衡量她的吉泰的RCT，并支持她成功转型为一名独立调查员。

Over 1/3 of adolescents and young adults (AYAs) who have undergone kidney or liver transplantation are nonadherent to immunosuppressant medicine, a leading cause of organ rejection, graft failure, and death. Despite the American Society of Transplantation's calls for real-time approaches to address immunosuppressant nonadherence, there are no validated metrics using real-time adherence data (e.g., electronic pillboxes) to identify those at risk for rejection and no efficacious interventions that leverage these data to improve adherence. Hence, we will fill these critical gaps in nonadherence management by validating the new “Real-Time Adherence Measure,” a novel instrument that could revolutionize how nonadherence is detected by linking the precision of non-invasive, easily downloaded, timestamped electronic pillbox data to tacrolimus blood level standard deviations (biological index of drug ingestion) to direct in the moment when immunosuppressant nonadherence leads to rejection. We will harness this real-time daily dosing information in an adherence-promoting just-in-time adaptive intervention (JITAI), a cutting-edge mobile health approach capable of fully incorporating AYAs' daily electronically-monitored adherence to deliver tailored intervention content exactly when the AYA needs it most. Currently, there are no JITAIs for this purpose. We will conduct this vital research, which involves using a micro- randomized trial, a state-of-the-art experimental design for creating successful JITAIs. To develop our JITAI, we will modify a promising existing intervention for promoting AYA adherence (sent adherence support messages when dose was due) by triggering adherence support messages only when medicine is missed and providing praise messages when medicine is taken. A JITAI-version of this intervention will be piloted with AYA kidney or liver transplant recipients in a 12-week micro-randomized trial to identify intervention content and timing that maximize the JITAI's impact on adherence. AYAs will be randomized after each electronically-monitored missed tacrolimus dose to receive (1) an adherence support message or (2) no message. After each on time dose, AYAs will be randomized to receive (1) a praise message or (2) no message. AYAs' engagement in the JITAI will be qualitatively characterized to support long-term uptake. Our findings will address significant knowledge gaps in how to optimally leverage technology to effectively measure and improve medication adherence for AYA kidney or liver transplant recipients, reduce nonadherence-related rejection, graft loss, and death, and improve people's health and quality of life. Dr. Eaton's study and training activities will prepare her to use advanced methodologies to validate novel clinical metrics, design JITAIs, conduct micro-randomized trials, and improve mobile health engagement. It is critical for Dr. Eaton to have support from this K23 to attain expertise in these innovative methods and to achieve her important scientific aims. Dr. Eaton's career development activities will occur at Johns Hopkins. Results of this study will provide essential preliminary data for Dr. Eaton's R01-supported full- scale RCT of her JITAI and support her successful transition to become an independent investigator.