关键词: 靶向临床试验, 样本量, 把握度, 富集设计, 全随机设计, 策略设计

Abstract: AIM: In recent years, the targeted clinical trials increase rapidly with various design methods. The choice of these design methods, however, has not been widely recognized. In this paper, we conducted a simulation study to assess the statistical performance of three commonly used targeted clinical trial design methods to provide evidence for design choice.METHODS: For three commonly used targeted clinical trial design methods (full randomized design, enrichment design and strategy design); we investigated the relationship between sample size and statistical power under different parameters to compare the statistical performance of the design methods by simulation method.RESULTS: If two groups were assigned with the same sample size, the enrichment design always obtained the largest power. Except the condition that targeting therapeutic drugs had adverse effect on target negative patients, the full randomized design can obtain larger power than the strategy design. When the targeted drugs also had a certain beneficial effect for the target negative patients, the enrichment design required larger sample size for screening than the full randomized design to maintain the same power.CONCLUSION: If the targeted drugs have a certain effect for non-target patients, or there is no accurate diagnosis of target and the target positive rate in patients is high, we recommend the full randomized design with subgroup analysis.

Key words: Targeted clinical trial, Sample size, Power, Enrichment design, Full randomized design, Strategy design