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学中心（CCHMC）行为医学和临床心理学部门的助理教授。这项K23应用结合了神经学、药理学和行为心理学方面的指导，与新发癫痫儿童抗癫痫药物治疗（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，使用AED血清水平的药代动力学建模，以开发一种客观的依从性生物标志物，并为开发临床干预试验提供培训，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果措施，并实施基于证据的干预措施以提高依从性。候选人的职业规划利用了CCHMC的专业知识，以增加儿童癫痫依从性行为方面的先前和计划培训。此外，候选人所在部门承诺在其早期教师任命期间提供至少75%的受保护研究时间和可用资源（例如，计算机，办公空间），使CCHMC成为此类奖项的理想机构。因此，候选人建议在全国知名临床研究者的指导下进行为期五年的强化指导和培训，学习与药代动力学建模和治疗药物监测、纵向设计和统计分析、临床试验方法学、拨款写作技巧和研究伦理相关的课程。提出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预测AED血清浓度的PK差异（例如残留）与观察到的血清浓度和电子监测的依从性之间的关联，来验证一个客观的依从性生物学标记。本研究的第二个目的是根据一个概念模型确定与依从性差相关的疾病/方案、父母和儿童因素，确定有效的干预目标。最后，从目标1（依从性的客观标记）和目标2（干预目标）中获得的信息将用于制定、完善和手动操作一种行为干预措施，以提高新发癫痫患儿的依从性。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在儿童癫痫依从性领域建立成功的独立研究生涯提供必要的早期职业支持。与公共卫生的相关性：儿童癫痫影响32.5万名儿童。该候选人的成功对公共卫生具有重大意义，因为设计有效的依从性干预措施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.