Ivanova Anastasia, Murphy Michael
Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7420, USA.
J Biopharm Stat. 2009;19(2):247-55. doi: 10.1080/10543400802609805.
The primary objective of the dose-escalation trial for NGX267 was to estimate the maximally tolerated dose (MTD) and to gather detailed clinical and pharmacokinetic observations near the MTD. The MTD was defined based on the weighted average of moderate and severe adverse events. An adaptive design was employed to concentrate dosage assignments at or near the MTD. Favoring the acquisition of data near the MTD, at the expense of information at lower dosage levels, resulted in a shorter trial and no loss of the type of information required to inform subsequent studies where larger normal volunteer or patient samples are evaluated.
NGX267剂量递增试验的主要目的是估计最大耐受剂量（MTD），并收集接近MTD时的详细临床和药代动力学观察数据。MTD是根据中度和重度不良事件的加权平均值来定义的。采用了适应性设计，以便将剂量分配集中在MTD或其附近。以较低剂量水平的信息为代价，倾向于获取接近MTD的数据，从而缩短了试验时间，并且没有丢失后续评估更大规模正常志愿者或患者样本的研究所需要的信息类型。
