基于外推的抗癫痫药儿科临床研究策略

Extrapolation-based Clinical Trial Design Strategies for Pediatric Antiepileptic Drugs

抗癫痫药物(AED)是治疗儿童癫痫的基石和首选手段,然而在儿童人群中通过随机对照临床试验评价其有效性困难,造成儿童AED新药研发明显滞后。该研究综述了外推理念在儿童AED研发中应用的理论基础、发展历史和现状,以及基于外推理念的儿童AED临床研究策略。结果显示,局灶性癫痫发作(FOS)治疗药物的成人有效性向1个月以上儿童患者的外推已被接受。儿童外推计划应包括:儿童适宜性剂型的开发、儿童药动学(PK)研究和长期安全性研究的合理设计以及采用模型引导的方法筛选儿童剂量。

Antiepileptic drugs(AED)are the cornerstone and first-choice of the treatment for childhood epilepsy.However,due to the difficulty of evaluating efficacy by randomized controlled trials in the pediatric population,the development of new AEDs for children is delayed.This paper reviews the evidence,history and current thoughts of applying extrapolation method into the development of pediatric AEDs.Besides,the extrapolation-based strategies for pediatric clinical trial design are also illustrated.The results show that the efficacy of drugs treating focal onset seizures(FOS)currently could be extrapolated from adults to pediatric patients 1 month of age and older.The pediatric extrapolation plans should include:the development of pediatric formulations,the rational design of pediatric pharmacokinetics(PK)study and long-term safety study,as well as model-informed dose selection for antiepileptic drugs in pediatrics.