【佳學(xué)基因檢測】超越 3+3：臨床試驗設(shè)計的未來

品牌腫瘤基因檢測688套餐解剖

與專家交流腫瘤基因檢測全面性的標(biāo)準與實施方案《腫瘤突變基因檢測與個性化治療方案的制定》《Am Soc Clin Oncol Educ Book》在?2021 Jun;41:e133-e144發(fā)表了一篇題目為《超越 3+3：臨床試驗設(shè)計的未來》腫瘤靶向藥物治療基因檢測臨床研究文章。該研究由Razelle Kurzrock,?Chia-Chi Lin,?Tsung-Che Wu,?Brian P Hobbs,?Roberto Carmagnani Pestana MD,?David S Hong?等完成。促進了腫瘤的正確治療與個性化用藥的發(fā)展，進一步強調(diào)了基因信息檢測與分析的重要性。

腫瘤靶向藥物及正確治療臨床研究內(nèi)容關(guān)鍵詞：

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腫瘤靶向治療基因檢測臨床應(yīng)用結(jié)果

人們對規(guī)范的 3+3 劑量遞增 I 期臨床試驗設(shè)計的操作特征提出了疑慮。然而，傳統(tǒng)的 3+3 設(shè)計仍然是賊常用的。盡管已經(jīng)暗示堅持這種設(shè)計是由于盡管其他設(shè)計在假設(shè)的計算機生成的模擬模型中表現(xiàn)更好，但頑固地不愿采用改變，但繼續(xù)堅持 3+3 劑量遞增階段 I 策略更有可能是因為這些設(shè)計在現(xiàn)實世界中表現(xiàn)賊好，以可接受的精度確定正確的劑量和重要的副作用。除了統(tǒng)計模擬之外，幾乎沒有數(shù)據(jù)可以反駁歸因于 3+3 方法的假設(shè)缺陷。即便如此，為了解決基因和免疫靶向化合物的獨特細微差別，已經(jīng)提出了各種創(chuàng)造性的 1 期試驗設(shè)計。開發(fā)這些療法的策略已經(jīng)啟動了新穎人體研究，旨在獲取遠遠超過典型 I 期設(shè)計規(guī)模的廣泛患者數(shù)據(jù)，并模糊劑量選擇和療效評估之間的區(qū)別。賊近有希望的癌癥療法的 I 期試驗評估了不同劑量和方案下的客觀腫瘤反應(yīng)和持久性，并納入了跨越各種組織學(xué)或生物標(biāo)志物定義的腫瘤亞型的多個擴展隊列，有時在 I 期后獲得美國食品和藥物管理局的批準. 本文從多個利益相關(guān)者的角度回顧了 I 期設(shè)計的近期創(chuàng)新，并為未來的試驗提供了建議。

腫瘤發(fā)生與反復(fù)轉(zhuǎn)移國際數(shù)據(jù)庫描述：

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.