Novel Adherence Measurement and Intervention in Children with New-Onset Epilepsy

描述（由申请人提供）：K23候选人是辛辛那提儿童医院医疗中心（CCHMC）行为医学和临床心理学部门的助理教授。这个K23应用程序结合了神经学，药理学和行为心理学方面的指导，这些指导与新发癫痫儿童的抗癫痫药物治疗（AED）的依从性有关。拟议的职业发展计划将为候选人提供必要的培训，以使用AED血清水平的药代动力学建模来开发依从性的客观生物标志物，并在临床干预试验的开发中进行培训，以提高依从性。需要在这些领域进行培训，以制定可靠的依从性结局指标，并实施循证干预措施以提高依从性。候选人的职业计划利用CCHMC的专业知识，以加强在儿童癫痫的行为方面的依从性的先前和计划的培训。此外，候选人所在部门的承诺涉及至少75%的保护研究时间在她的早期教师任命和可用资源（例如，计算机，办公空间）使CCHMC成为此类奖项的理想机构。因此，候选人提出了一个为期五年的强化指导和培训计划，由全国知名的临床研究人员，与药代动力学建模和治疗药物监测，纵向设计和统计分析，临床试验方法，赠款写作技巧和研究伦理相关的课程。拟议的研究计划包括三个主要目标。该研究的第一个目的是通过测量差异（例如，残差）的PK预测AED血清浓度和观察到的血清浓度和电子监测的依从性。本研究的第二个目的是根据一个概念模型确定有效的干预目标，该模型确定了与依从性差相关的疾病/方案、父母和儿童因素。最后，从目标1（依从性的客观标志物）和目标2（干预目标）中获得的信息将用于开发、完善和手动化行为干预，以改善新发癫痫儿童的依从性。从候选人的职业发展和研究计划中获得的综合技能和经验将为候选人提供必要的早期职业支持，以在儿科癫痫的坚持领域建立成功的独立研究职业生涯。与公共卫生的相关性：儿科癫痫影响了325，000名儿童。候选人的成功与公共卫生具有重要的相关性，因为有效的依从性干预措施的设计可以改善癫痫儿童及其家庭的健康结果和生活质量。

DESCRIPTION (provided by applicant): The K23 Candidate is an assistant professor in the Division of Behavioral Medicine and Clinical Psychology at Cincinnati Children's Hospital Medical Center (CCHMC). This K23 application combines mentoring in neurology, pharmacology, and behavioral psychology that relates to adherence of antiepileptic drug therapy (AED) in children with new-onset epilepsy. The proposed career development plan will provide the candidate necessary training in the use of pharmacokinetic modeling of AED serum levels needed to develop an objective biological marker of adherence and training in the development of clinical intervention trials to improve adherence. Training in these areas is needed to develop reliable outcome measures of adherence and implement an evidence-based intervention to improve adherence. The candidate's career plan capitalizes on the expertise at CCHMC to augment prior and planned training in the behavioral aspects of adherence in pediatric epilepsy. In addition, the commitment of the candidate's division related to at least 75 percent protected research time during her early faculty appointment and resources available (e.g., computers, office space) make CCHMC an ideal institution for such an award. The candidate thus proposes a five-year program of intensive mentorship and training by nationally renowned clinical investigators, courses related to pharmacokinetic modeling and therapeutic drug monitoring, longitudinal design and statistical analyses, clinical trials methodology, grant writing skills, and research ethics. The proposed research plan consists of three major aims. The first aim of the study is to validate an objective, biological marker of adherence by measuring the association between the difference (e.g., residual) of PK predicted AED serum concentrations and observed serum concentrations and electronically monitored adherence. The second aim of the study is to identify valid targets for intervention based on a conceptual model that identifies disease/regimen, parent, and child factors associated with poor adherence. Finally, information obtained from Aims 1 (objective marker of adherence) and 2 (targets for intervention) will be utilized to develop, refine, and manualize a behavioral intervention to improve adherence in children with new-onset epilepsy. The combined skill set and experience garnered from the candidate's career development and research plans will provide the necessary early career support for the candidate to establish a successful independent research career in the area of adherence in pediatric epilepsy. Relevance to Public Health: Pediatric epilepsy affects 325,000 children. The candidate's success has significant relevance to public health as the design of effective adherence interventions could improve both health outcomes and quality of life for children with epilepsy and their families.