论文标题
I期剂量降低研究中的回填充队
Backfilling Cohorts in Phase I Dose-Escalation Studies
论文作者
论文摘要
使用“回填”，将其他患者分配给被认为是安全的剂量，在I期剂量降低研究中已被使用，以收集有关药物的安全性，药代动力学和活动的其他信息。这些额外的患者有助于确保可靠地估计最大耐受剂量（MTD），并提供其他信息以确定建议的II期剂量（RP2D）。在本文中，我们研究了在I期试验中采用回填对MTD估计和研究持续时间的影响。我们考虑只有一个随访周期来升级的情况以及可能延迟发作毒性的情况。我们发现，在各种情况下，正确选择的比例有所增加，并且试验持续时间显着减少，以研究中需要更多的患者为代价。
The use of `backfilling', assigning additional patients to doses deemed safe, in phase I dose-escalation studies has been used in practice to collect additional information on the safety profile, pharmacokinetics and activity of a drug. These additional patients help ensure that the Maximum Tolerated Dose (MTD) is reliably estimated and give additional information in order to determine the recommended phase II dose (RP2D). In this paper, we study the effect of employing backfilling in a phase I trial on the estimation of the MTD and the duration of the study. We consider the situation where only one cycle of follow-up is used for escalation as well as the case where there may be delayed onset toxicities. We find that, over a range of scenarios, there is an increase in the proportion of correct selections and a notable reduction in the trial duration at the cost of more patients required in the study.
