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

描述（由申请人提供）：本修订后的多中心提案利用了现有的儿童肝移植研究（SPLIT）注册表，并辅以额外的前瞻性数据，以测试接受肝移植的儿童对免疫抑制药物依从性的客观测量。不依从性是儿童肝移植长期存活者器官排斥的最重要原因。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来识别这些儿童的不依从性。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坚持。计算每位患者血液中药物水平随时间的波动程度，可以识别出不依从性（波动越大=服药越不一致=依从性越差）。药物血药浓度的波动程度与排斥反应有关。该资助评估了该方法（计算药物血液水平的可变性）以及其他辅助依从性措施在一大群移植患者中的使用情况。它决定了依从性的“阈值”（不依从性何时开始与器官排斥有关）。本建议还利用前瞻性随访队列来评估不依从的心理社会预测因素。这些预测因素可用于告知干预措施，以提高依从性。由于该建议将验证一种临床有用的方法来评估依从性，结果有望提高儿童移植受者的生存率并减少排斥反应。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、不依从性的生物标记物可以用于其他人群。此外，检测方法将为支持移植环境中的依从性研究（如治疗策略）提供必要的基础，其结果可以推广到其他环境。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药物，但许多人停止服用它们。该提案将验证一种方法，以识别因未服用药物而处于危险中的儿童。结果将有助于移植中心识别这些儿童，提高移植后的总体存活率，也将为其他可能不按规定服药的儿童提供信息。

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.