Garofalo Elizabeth
University of Michigan School of Medicine, Ann Arbor, Michigan 48103, USA.
Neurotherapeutics. 2007 Jan;4(1):70-4. doi: 10.1016/j.nurt.2006.10.004.
A clinical development plan specific to children is a necessary component of every development plan for a new antiepileptic drug (AED). In the last decade, considerable discussion has occurred in the medical and regulatory communities, resulting in specific pediatric drug development legislation. Ethical issues are a foremost consideration in the design and conduct of studies. The timing of clinical studies differs between adults and children. In general, studies in children will not be performed until efficacy and safety has been demonstrated in adults. Exceptions include development of AEDs for seizure types seen only in children. Formulation preparation and dosing selection are often more challenging in children. Clinical trials including pharmacokinetic studies will be conducted in patients. A relatively small number of children, given subdivision into age groups and seizure types, are available for study. Clinical trials must be designed with children in mind, adjusting the length of the trials and the choice of controls. Efficacy extrapolation from adults may be considered for partial seizures in children, but not in infants. Seizure counts remain an appropriate efficacy endpoint; however, ascertainment in infants and younger children may require EEG monitoring. Safety specific to growing and developing children must be evaluated and long-term effects monitored.
针对儿童的临床开发计划是每种新型抗癫痫药物（AED）开发计划的必要组成部分。在过去十年中，医学和监管界进行了大量讨论，从而产生了特定的儿科药物开发立法。伦理问题是研究设计和实施中首要考虑的因素。成人和儿童临床研究的时间安排有所不同。一般来说，在儿童中进行研究之前，需先在成人中证明其疗效和安全性。例外情况包括仅针对儿童中出现的癫痫发作类型开发的AED。在儿童中，制剂制备和剂量选择通常更具挑战性。包括药代动力学研究在内的临床试验将在患者中进行。由于要细分为年龄组和癫痫发作类型，可供研究的儿童数量相对较少。设计临床试验时必须考虑到儿童，调整试验时长和对照选择。对于儿童部分性癫痫发作，可考虑从成人疗效进行外推，但婴儿不适用。癫痫发作次数仍然是合适的疗效终点；然而，在婴儿和年幼儿童中确定发作次数可能需要脑电图监测。必须评估儿童生长发育过程中的特定安全性，并监测长期影响。
