Improving Medication Adherence in children who had a Liver Transplant: iMALT

本次提交使用NIDDK的规划（U34）赠款机制。它是由领先的 儿科移植中心作为多中心努力的下一步，以验证 移植后免疫抑制药物的不依从性（药物依从性 肝移植后，MALT，多位点研究）。免疫抑制剂的不依从性是 是青少年移植受者器官排斥的主要原因。本提案的目的 计划进行一项多地点研究，调查一种量身定制的遥测干预， 移植结果（减少发生排斥反应的患者数量）， 接受肝移植的青少年的药物依从性。本研究将使用 药物水平变异性指数（MLVI），以确定干预措施的目标。MLVI是一种创新的 粘附生物标志物，其计算免疫抑制剂之间的变异程度 药物血液水平随时间的变化（变异性越高=依从性越差）。这是一个强大的预测， 器官排斥非粘附性高危青少年肝移植受者将通过使用 MLVI（MLVI>2表示临床上显著的不依从）。遥测干预 （通过电话、FaceTime ®或Skype ®界面管理）将使经验丰富的 干预者从远程位置解决不依从性，使用结构化的，定制的 适应特定患者需求的方法。这种方法包括解决 与自我护理相关的心理回避，还包括提醒和问题- 解决已确定的遵守障碍。由此产生的研究-一个随机对照试验- 将仅与高危患者接触，将通过MLVI标记持续监测其进展， 并将在整个2年试验期间根据依从性监测结果调整干预措施 期这项研究将探讨一种创新的“个性化医疗”方法， 远程干预工作。已经做了大量的初步工作，包括干预 试点;规划赠款期将用于最后确定议定书要素、成果措施 定义、监管和人类受试者研究文件和批准，以及培训 所有站点的人员。

This submission uses the NIDDK's planning (U34) grant mechanism. It is submitted by leading pediatric transplant centers as the next step of a multicenter effort to validate a marker for nonadherence to immunosuppressant medications post-transplant (the Medication Adherence after Liver Transplant, MALT, multisite study). Nonadherence to immunosupressants is the leading cause of organ rejection in adolescent transplant recipients. The present proposal's aim is to plan a multisite study that will investigate a tailored telemetric intervention to improve transplant outcomes (reduce the number of patients who have a rejection) by improving adherence to medications in adolescents who had a liver transplant. This study will use the Medication Level Variability Index (MLVI) to target the intervention. The MLVI is an innovative biomarker of adherence which calculates the degree of variability between immunosuppressant medication blood levels over time (higher variability = worse adherence). It is a robust predictor of organ rejection. Nonadherent at-risk adolescent liver transplant recipients will be identified using the MLVI (MLVI>2 denotes clinically significant nonadherence). The telemetric intervention (administered via telephone, FaceTime ® or Skype ® interfaces) will enable experienced interventionists to address nonadherence from a remote location, using a structured, tailored approach that accommodates specific patient needs. This approach includes addressing psychological avoidance associated with self-care, and further includes reminders and problem- solving of identified barriers to adherence. The resulting study – a randomized controlled trial – will engage at-risk patients only, will continually monitor their progress through the MLVI marker, and will tailor the intervention to the adherence monitoring findings throughout the 2 year trial period. This study will investigate an innovative “personalized medicine” approach to target a remote intervention effort. Substantial preliminary work has been done including intervention pilots; the planning grant period will be used to finalize protocol elements, outcome measures definitions, regulatory and human subjects study documents and approvals, and training of personnel at all sites.