FDA-AACR Strategies for Optimizing Dosages for Oncology Drug Products: Early-Phase Trials Using Innovative Trial Designs and Biomarkers.

Although this approach may have established optimized dosages for cytotoxic chemotherapeutics, many modern oncology drugs developed through this approach have been poorly optimized, requiring additional dosage optimization efforts in the postmarket setting.

尽管这种方法可能为细胞毒性化疗药物建立了优化剂量，但许多通过这种方法开发的现代肿瘤药物在市场后需要额外的剂量优化努力。

Recent initiatives of the FDA outline the unsustainability of this approach, instead recommending the identification of a potentially optimized dosage at earlier stages through a direct comparison of multiple dosages before marketing application submission.

FDA最近的举措概述了这种方法的不可持续性，反而建议在市场申请提交之前，通过比较多种剂量，早期确定一个可能优化的剂量。

The selection of dosages for further investigation outside of the MTD requires fit-for-purpose techniques that address the specific promises and concerns of the drug under investigation.

在MTD之外选择进一步研究的剂量，需要适用的技术来解决正在研究的药物的具体承诺和问题。

Although such strategies have been developed, they are currently rarely applied in favor of the MTD paradigm.

尽管已经开发了这样的策略，但目前它们很少被应用，而是倾向于最大耐受剂量（MTD）范式。

Innovative trial elements, including various integral, integrated, and exploratory biomarkers as well as backfill and randomized dose-expansion cohorts, represent potential avenues to create and leverage additional data and thereby make more informed dosing decisions.

创新的试验元素，包括各种综合的、集成的和探索性的生物标志物以及补充和随机剂量扩展队列，代表了创造和利用额外数据的潜在途径，从而做出更明智的剂量决策。

Additionally, modeling approaches such as clinical utility index can integrate these disparate datatypes into a single metric, facilitating more quantitative selection.

此外，临床效用指数等建模方法可以将这些不同的数据类型整合到一个单一的指标中，从而促进更定量的选择。

This article, the second in a series of three articles addressing different stages of dose optimization, outlines best practices and areas for further development with regard to innovative techniques for the selection of dosages for further evaluation prior to final dosage selection for registrational trials in oncology.

这篇文章是关于剂量优化不同阶段的三篇文章中的第二篇，概述了在最终剂量选择用于肿瘤学注册试验之前，选择用于进一步评估的剂量的最佳实践和进一步发展的领域，涉及创新技术。