Simon Richard, Maitournam Aboubakar
Biometric Research Branch, National Cancer Institute, Bethesda, Maryland 20892-7634, USA.
Clin Cancer Res. 2004 Oct 15;10(20):6759-63. doi: 10.1158/1078-0432.CCR-04-0496.
Genomic technologies make it increasingly possible to identify patients most likely to benefit from a molecularly targeted drug. This creates the opportunity to conduct targeted clinical trials with eligibility restricted to patients predicted to be responsive to the drug.
We evaluated the relative efficiency of a targeted clinical trial design to an untargeted design for a randomized clinical trial comparing a new treatment to a control. Efficiency was evaluated with regard to number of patients required for randomization and number required for screening.
The effectiveness of this design, relative to the more traditional design with broader eligibility, depends on multiple factors, including the proportion of responsive patients, the accuracy of the assay for predicting responsiveness, and the degree to which the mechanism of action of the drug is understood. Explicit formulas were derived for computing the relative efficiency of targeted versus untargeted designs.
Targeted clinical trials can dramatically reduce the number of patients required for study in cases where the mechanism of action of the drug is understood and an accurate assay for responsiveness is available.
基因组技术使得越来越有可能识别出最有可能从分子靶向药物中获益的患者。这创造了开展靶向临床试验的机会，其入选标准仅限于预计对该药物有反应的患者。
我们评估了靶向临床试验设计与非靶向设计在一项将新治疗方法与对照进行比较的随机临床试验中的相对效率。从随机分组所需患者数量和筛查所需患者数量方面对效率进行了评估。
相对于入选标准更宽泛的传统设计，该设计的有效性取决于多个因素，包括有反应患者的比例、预测反应性检测方法的准确性以及对药物作用机制的了解程度。推导了用于计算靶向设计与非靶向设计相对效率的明确公式。
在了解药物作用机制且有准确的反应性检测方法的情况下，靶向临床试验可显著减少研究所需的患者数量。
