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Ⅰ期临床试验主要关心毒性,通常划分毒性为五个水平．简单起见,同时兼顾伦理问题,Ⅰ期临床试验通常采用up-and-down序贯设计(例如BCDⅠ,BCDⅡ,K-in-a-row,Narayana,Improved Narayana)．然而,在分配剂量水平时,该设计没有区分已经试验了的病人的严重毒性水平等级,从而有可能分配给病人更高毒性的剂量水平．因此,本文提出了基于药物毒性等级确定最大耐受剂量的up-and-down设计方法,并进一步研究了该设计方法在各种变化的剂量—毒性关系下的运作特征,并且和标准的up-and-down设计作模拟比较,结果表明该设计方法对Ⅰ期临床试验设计的剂量建议具有重要意义．
Phase I clinical trials are primarily concerned with toxicity, usually dividing the toxicity into five levels. For simplicity, while taking ethical issues into consideration, Phase I clinical trials usually use up-and-down sequential design (eg BCDI, BCDII, K-in-a-row, Narayana, Improved Narayana). However, at the time of dispensing dose levels, the design did not differentiate between the severity levels of the toxicants already tested, making it possible to assign the patient to more toxic dosage levels. Therefore, this paper presents an up-and-down design approach to determine maximum tolerated dose based on drug toxicity level and further studies the operational characteristics of this design approach under various dose-toxicity relationships and correlates well with the standard up- and-down design as a simulation comparison, the results show that the design method for the phase Ⅰ clinical trial design dose recommendations of great significance.