New clinical research strategies in thoracic oncology: clinical trial design, adaptive, basket and umbrella trials, new end-points and new evaluations of response.
New clinical research strategies in thoracic oncology: clinical trial design, adaptive, basket and umbrella trials, new end-points and new evaluations of response.
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DOI：
10.1183/09059180.00004214
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发表时间：
2014-09
影响因子：
7.5
通讯作者：
Besse, Benjamin
中科院分区：
文献类型：
--
作者：
Menis, Jessica;Hasan, Baktiar;Besse, Benjamin
在基因组学时代，我们的主要目标应该是在小的、分子选择的患者群体中识别出大的和有意义的差异。药物开发的经典第一阶段、第二阶段和第三阶段模型需要大量资源，限制了可以测试的实验试剂的数量，并使靶向药物的评估效率低下。迫切需要简化新化合物的开发，以确定“为学习而设计的试验”，这可能导致随后的“为得出结论而设计的试验”。篮子试验通常被视为同一实体内的平行第二阶段试验，根据一个共同的分母设计，这可能是一个分子改变(S)。大多数篮子试验都是组织学独立的和畸变学特异的临床试验。伞状试验建立在中央执行的分子画像和分子选择的具有匹配药物的队列的基础上，可以包括患者的随机化和策略验证。除了新的设计，新的终点和新的评估技术也是必要的，以最终实现方法学和临床改进，特别是在免疫治疗试验中。
In the genomics era, our main goal should be to identify large and meaningful differences in small, molecularly selected groups of patients. Classical phase I, II and III models for drug development require large resources, limiting the number of experimental agents that can be tested and making the evaluation of targeted agents inefficient. There is an urgent need to streamline the development of new compounds, with the aim of identifying “trials designed to learn”, which could lead to subsequent “trials designed to conclude”. Basket trials are often viewed as parallel phase II trials within the same entity, designed on the basis of a common denominator, which can be a molecular alteration(s). Most basket trials are histology-independent and aberration-specific clinical trials. Umbrella trials are built on a centrally performed molecular portrait and molecularly selected cohorts with matched drugs, and can include patients’ randomisation and strategy validation. Beyond new designs, new end-points and new evaluation techniques are also warranted to finally achieve methodology and clinical improvements, in particular within immunotherapy trials.