0期临床试验:新药临床研究的新模式

0期临床试验是一种先于传统的Ⅰ期临床试验开展的研究,旨在评价受试药物的药效动力学和药代动力学特征。0期试验的特点是:小剂量、短周期、少量受试者、不以药物疗效评价为目的。0期试验主要用于作用靶点指标和(或)生物标记物的抗肿瘤候选药物的药效学和药动学评价。一般可将0期临床研究的类型分为3类。开展0期临床研究可参考美国食品与药品监督管理局的"探索性研究药物指南"。0期临床试验的局限性可以通过良好的试验设计加以克服。对于分子靶向的抗癌药物,0期临床研究可提高研究效率和后续研究的成功率。

Phase 0 clinical trial: a new way to successful clinical trial for candidate drugs

Phase 0 trials are designed primarily to evaluate the pharmacodynamic and/or pharmacokinetic properties of selected investigational agents before initiating traditional phase I testing. In a phase 0 trial, the pharmacodynamic effects of an investigational agent are evaluated by a target or biomarker which is measured by an assay established and validated in preclinical models. The phase 0 trial is characterized by a small number of patients enrolled and limited dosing period with a non-therapy-intended dose range. Furthermore, phase 0 trials are classified into three types and conducted under the US Food and Drug Administration exploratory investigational new drug guidance with less preclinical toxicity data than usually required for traditional first-in-human studies. A well designed and executed phase 0 trial can overcome its limitations and has a great potential for improving the efficiency and success of subsequent trials, particularly those evaluating molecularly targeted antitumor candidates.