Emory University, Atlanta, Georgia, USA.
Epileptic Disord. 2012 Jun;14(2):114-23. doi: 10.1684/epd.2012.0510.
A golden age of antiepileptic drug development has yielded over a dozen useful new compounds, but the nature of clinical trials has made translation to practical use in the clinic difficult. Most clinical trials are designed for regulatory purposes and fail to answer critical clinical questions. These questions include: which drug is best as initial therapy, which drugs work as monotherapy, what are good drug combinations, what is the best starting dose and titration schedule, what is a reasonable target dose, what is the shape of the dose-response curve and does it vary significantly between patients, what is the true incidence of side effects, and what is the long-term efficacy of the drug? Most of these questions could be answered by changing trial designs, but many changes would entail additional time and money. There are encouraging signs that trials with procedures more directly applicable to the clinic are becoming common. These include direct comparative trials, longer trials with emphasis on seizure freedom, and trials with more flexible dosing schedules. In the past, funding of longer and more naturalistic trials has fallen to government agencies, but commercial funding has been obtained for several recent studies. Better quality control, innovative endpoints, structured searching for side effects, and standardisation of data collection are also promising topics for development.
抗癫痫药物研发的黄金时代已经产生了十几种有用的新化合物，但临床试验的性质使得它们难以转化为临床实际应用。大多数临床试验都是为监管目的而设计的，无法回答关键的临床问题。这些问题包括：哪种药物作为初始治疗最好，哪种药物作为单药治疗有效，哪些药物联合使用效果好，最佳起始剂量和滴定方案是什么，合理的目标剂量是多少，剂量-反应曲线的形状如何，以及它在患者之间是否有显著差异，副作用的真实发生率是多少，以及药物的长期疗效如何？大多数这些问题都可以通过改变试验设计来回答，但许多改变都需要额外的时间和资金。有一些令人鼓舞的迹象表明，更直接适用于临床的试验正在变得普遍。这些包括直接比较试验、强调无癫痫发作的更长时间试验，以及更灵活剂量方案的试验。过去，政府机构为更长时间和更自然的试验提供资金，但最近有几项研究已经获得了商业资金。更好的质量控制、创新性的终点、对副作用的有组织搜索以及数据收集的标准化也是有前途的发展领域。
