Guo Wentian, Ji Yuan, Li Daniel
a Laiya Consulting, Inc ., Wilmette , Illinois , USA.
b Research Institute , NorthShore University HealthSystem , Evanston , Illinois , USA.
J Biopharm Stat. 2019;29(3):411-424. doi: 10.1080/10543406.2019.1577683. Epub 2019 Feb 11.
To shorten trial duration and improve safety of Phase I trials, we propose R-TPI, a rolling enrollment design that combines the features in model-based designs such as mTPI-2 and rule-based designs such as rolling six. R-TPI employs a novel rolling enrollment scheme, which allows concurrent patient enrollment that is faster than cohort-based enrollment. Bench-marking against rolling six, we find that the R-TPI design is as fast in completing clinical trials but with fewer toxicity events and higher chance of finding the maximum tolerated dose (MTD) in the single scenario laid out in the 2008 rolling six publication. We also find that in a broad setting involving multiple scenarios, R-TPI is generally faster, safer, and more reliable than standard designs. R-TPI is a general design that can be applied to adult and pediatric Phase I trials. It reduces the length of trial duration, leads to safer trials with fewer toxicity events, and maintains relatively a high chance of identifying the MTD.
为缩短Ⅰ期试验的持续时间并提高其安全性，我们提出了R-TPI，这是一种滚动入组设计，它结合了基于模型的设计（如mTPI-2）和基于规则的设计（如滚动六法）的特点。R-TPI采用了一种新颖的滚动入组方案，该方案允许并行患者入组，其速度比基于队列的入组更快。与滚动六法进行基准对比，我们发现R-TPI设计在完成临床试验方面同样迅速，但在2008年滚动六法出版物中列出的单一情况下，毒性事件更少，找到最大耐受剂量（MTD）的几率更高。我们还发现，在涉及多种情况的广泛背景下，R-TPI通常比标准设计更快、更安全且更可靠。R-TPI是一种通用设计，可应用于成人和儿科Ⅰ期试验。它缩短了试验持续时间，使试验更安全，毒性事件更少，并保持了相对较高的识别MTD的几率。
