N OF 1 RANDOMIZED TRIALS FOR INVESTIGATING NEW DRUGS
N OF 1 RANDOMIZED TRIALS FOR INVESTIGATING NEW DRUGS
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DOI：
10.1016/0197-2456(90)90003-k
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发表时间：
1990-04-01
期刊：
影响因子：
--
通讯作者：
ROBERTS, RS
中科院分区：
文献类型：
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作者：
GUYATT, GH;HEYTING, A;ROBERTS, RS
目前，在新药开发过程中，大样本平行分组随机试验往往是在没有详细了解最佳剂量、最敏感的患者组和理想的最佳结果的情况下开始的。我们建议，在药物开发的早期阶段，可以使用针对单个受试者的随机试验(N个随机对照试验)来阐明这些问题。在适当的条件下，1个随机对照试验中的N个可用于定义药物开始和停止临床作用的速度、最佳药物剂量的可能范围以及后续试验应关注的最佳结果。1个随机对照试验中的N个也可以生成对新药物有反应的患者比例的初步估计，并为后续的平行团体试验确定样本量、纳入标准和剂量方案(S)。我们提供了14个N/1阿米替林随机对照试验治疗纤维炎的例子，说明了N/1随机对照试验可以阐明这些问题的方法。N/1随机对照试验的多次使用表明，该方法在药物开发计划的早期阶段具有巨大的潜力。
Presently, in the process of new drug development, large sample parallel group randomized trails are often begun without the detailed knowledge of optimal dose, most responsive patient group, and optimal outcomes which would be desirable. We propose that randomized trials in individual subjects (N of 1 RCTs) could be used to elucidate these issues at an early stage of drug development. In appropriate conditions N of 1 RCTs can be used to define the rapidity with which a drug begins and ceases its clinical action, the likely range of the optimal drug dose, and the optimal outcomes on which subsequent trials should focus. N of 1 RCTs can also generate initial estimates of the proportion of patients who respond to a new agent and for determining sample size, inclusion criteria, and dosage regimen(s) for subsequent parallel group trials. We provide an example of 14 N of 1 RCTs of amitriptyline in fibrositis that illustrate the ways in which N of 1 RCTs can elucidate these issues. The multiple uses of N of 1 RCTs suggest that he method has immense potential for use in the early phases of drug development programs.