【佳学基因检测】超越 3+3：临床试验设计的未来

品牌肿瘤基因检测688套餐解剖

与专家交流肿瘤基因检测全面性的标准与实施方案《肿瘤突变基因检测与个性化治疗方案的制定》《Am Soc Clin Oncol Educ Book》在 2021 Jun;41:e133-e144发表了一篇题目为《超越 3+3：临床试验设计的未来》肿瘤靶向药物治疗基因检测临床研究文章。该研究由Razelle Kurzrock, Chia-Chi Lin, Tsung-Che Wu, Brian P Hobbs, Roberto Carmagnani Pestana MD, David S Hong 等完成。促进了肿瘤的正确治疗与个性化用药的发展，进一步强调了基因信息检测与分析的重要性。

肿瘤靶向药物及正确治疗临床研究内容关键词：

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肿瘤靶向治疗基因检测临床应用结果

人们对规范的 3+3 剂量递增 I 期临床试验设计的操作特征提出了疑虑。然而，传统的 3+3 设计仍然是贼常用的。尽管已经暗示坚持这种设计是由于尽管其他设计在假设的计算机生成的模拟模型中表现更好，但顽固地不愿采用改变，但继续坚持 3+3 剂量递增阶段 I 策略更有可能是因为这些设计在现实世界中表现贼好，以可接受的精度确定正确的剂量和重要的副作用。除了统计模拟之外，几乎没有数据可以反驳归因于 3+3 方法的假设缺陷。即便如此，为了解决基因和免疫靶向化合物的独特细微差别，已经提出了各种创造性的 1 期试验设计。开发这些疗法的策略已经启动了新颖人体研究，旨在获取远远超过典型 I 期设计规模的广泛患者数据，并模糊剂量选择和疗效评估之间的区别。贼近有希望的癌症疗法的 I 期试验评估了不同剂量和方案下的客观肿瘤反应和持久性，并纳入了跨越各种组织学或生物标志物定义的肿瘤亚型的多个扩展队列，有时在 I 期后获得美国食品和药物管理局的批准. 本文从多个利益相关者的角度回顾了 I 期设计的近期创新，并为未来的试验提供了建议。

肿瘤发生与反复转移国际数据库描述：

Misgivings have been raised about the operating characteristics of the canonical 3+3 dose-escalation phase I clinical trial design. Yet, the traditional 3+3 design is still the most commonly used. Although it has been implied that adhering to this design is due to a stubborn reluctance to adopt change despite other designs performing better in hypothetical computer-generated simulation models, the continued adherence to 3+3 dose-escalation phase I strategies is more likely because these designs perform the best in the real world, pinpointing the correct dose and important side effects with an acceptable degree of precision. Beyond statistical simulations, there are little data to refute the supposed shortcomings ascribed to the 3+3 method. Even so, to address the unique nuances of gene- and immune-targeted compounds, a variety of inventive phase 1 trial designs have been suggested. Strategies for developing these therapies have launched first-in-human studies devised to acquire a breadth of patient data that far exceed the size of a typical phase I design and blur the distinction between dose selection and efficacy evaluation. Recent phase I trials of promising cancer therapies assessed objective tumor response and durability at various doses and schedules as well as incorporated multiple expansion cohorts spanning a variety of histology or biomarker-defined tumor subtypes, sometimes resulting in U.S. Food and Drug Administration approval after phase I. This article reviews recent innovations in phase I design from the perspective of multiple stakeholders and provides recommendations for future trials.