Medication Adherence in Children Who Had a Liver Transplant (MALT)

描述（由申请方提供）：该修订后的多中心提案利用了现有的儿科肝移植研究（SPLIT）登记研究，并通过额外的前瞻性获得的数据进行了增强，以测试肝移植儿童对免疫抑制剂药物依从性的客观指标。不依从是小儿肝移植长期存活者发生器官排斥反应的最重要原因。为了有效地解决这一重要的风险因素，第一步是评估一种方法，可以识别这些儿童的不遵守。作为移植中心临床实践的一部分获得的药物血液水平可用于确定患者是否粘附。计算每个患者的药物血液水平随时间的波动程度将识别不依从性（波动越大=服药一致性越差=依从性越差）。药物血液水平的波动程度与排斥反应事件相关。该基金评估了这种方法（计算药物血液水平的变化）的使用，沿着其他辅助措施的遵守在一个大的移植患者群体。它确定了一个“阈值”的依从性（当不依从开始与器官排斥反应）。该建议还利用前瞻性随访队列来评估不依从的社会心理预测因素。这些预测因子可用于为干预措施提供信息，以提高依从性。由于这一提议将验证一种临床上有用的方法来评估依从性，因此预计结果将提高儿科移植受者的存活率并减少排斥反应。研究结果也有望为其他领域的依从性研究提供信息：这种新的、客观的非依从性生物学标记物可用于其他人群。此外，检测方法将提供必要的基础，以支持在移植设置（如治疗策略）的依从性研究，其结果可以推广到其他设置。公共卫生相关性：接受器官移植的儿童的生存依赖于免疫抑制剂药物，但许多人停止服用。这项提案将验证一种方法，以确定谁是儿童的风险，因为不采取他们的药物。这些结果将有助于移植中心识别这些儿童并提高移植后的总体生存率，并将告知儿童可能不按规定服用药物的其他医学领域。

DESCRIPTION (provided by applicant): This revised multi-center proposal takes advantage of the existing Studies in Pediatric Liver Transplant (SPLIT) registry augmented by additional prospectively-obtained data to test an objective measure of adherence to immunosuppressant medications in children who had a liver transplant. Nonadherence is the most important reason for organ rejection in long term survivors of pediatric liver transplantation. In order to address this important risk-factor effectively, the first step is to evaluate a method that would identify nonadherence in these children. Medication blood levels that are obtained as a part of clinical practice in transplant centers can be used to determine whether the patient is adherent or not. Calculating the degree of fluctuation of medication blood levels over time for each patient would identify nonadherence (more fluctuation = less consistent medication-taking = less adherence). The degree of fluctuation in medication blood levels is correlated with rejection episodes. This grant evaluates the use of this method (calculating the variability in medication blood levels) along with other ancillary measures of adherence in a large group of transplant patients. It determines a "threshold" of adherence (when does nonadherence begin to be associated with organ rejection). This proposal also takes advantage of the prospectively-followed cohort to evaluate psychosocial predictors for nonadherence. Those predictors can be used to inform intervention efforts to improve adherence. Since this proposal will validate a clinically- useful method to assess adherence, the results are expected to enhance survival and reduce rejections in pediatric transplant recipients. Results are also expected to inform adherence research in other fields: the novel, objective, biological marker for nonadherence can be used in other populations. Furthermore, the detection method will provide the essential basis to support adherence research in the transplant setting (such as treatment strategies), results from which can be generalized to other settings. PUBLIC HEALTH RELEVANCE: The survival of children who have received an organ transplant is dependent on immunosuppressant medications, but many stop taking them. This proposal will validate a method to identify children who are at risk because of not taking their medications. The results will help transplant centers identify these children and improve overall post transplant survival, and will also inform other areas of medicine in which children may not take their medications as prescribed.