论文标题

在肿瘤学试验中使用非连通的共同控制

Use of Non-concurrent Common Control in Master Protocols in Oncology Trials: Report of an American Statistical Association Biopharmaceutical Section Open Forum Discussion

论文作者

Sridhara, Rajeshwari, Marchenko, Olga, Jiang, Qi, Pazdur, Richard, Posch, Martin, Berry, Scott, Theoret, Marc, Shen, Yuan Li, Gwise, Thomas, Hess, Lorenzo, Raven, Andrew, Rantell, Khadija, Roes, Kit, Simon, Richard, Redman, Mary, Ji, Yuan, Lu, Cindy

论文摘要

本文总结了美国统计协会(ASA)生物制药(Biop)部分开放论坛的讨论,该论坛于2020年12月10日举行,由ASA Biop肿瘤学科学工作组的ASA Biop统计方法组织,与美国FDA肿瘤学中心协调。各种利益相关者在内,包括国际监管机构,院士和制药行业代表的专家,他们讨论了在肿瘤学试验的总体方案中使用非连续控制的讨论。尽管使用非连通控制与并发控制可能会增加检测治疗和控制之间的治疗差异的能力,但小组成员对建模非恒流和并发控制的统计方法有多样的看法。有些人更关心与时间相关的不同混杂因素引入的非交通控制和偏见的时间,例如,护理标准的变化,患者人群的变化,招聘策略的变化,端点评估的变化。然而,在某些情况下,例如当招募对罕见疾病极具挑战性时,小组成员得出结论认为,使用非交通控制是合理的。

This article summarizes the discussions from the American Statistical Association (ASA) Biopharmaceutical (BIOP) Section Open Forum that took place on December 10, 2020 and was organized by the ASA BIOP Statistical Methods in Oncology Scientific Working Group, in coordination with the US FDA Oncology Center of Excellence. Diverse stakeholders including experts from international regulatory agencies, academicians, and representatives of the pharmaceutical industry engaged in a discussion on the use of non-concurrent control in Master Protocols for oncology trials. While the use of non-concurrent control with the concurrent control may increase the power of detecting the therapeutic difference between a treatment and the control, the panelists had diverse opinion on the statistical approaches for modeling non-concurrent and concurrent controls. Some were more concerned about the temporality of the non-concurrent control and bias introduced by different confounders related to time, e.g., changes in standard of care, changes in patient population, changes in recruiting strategies, changes in assessment of endpoints. Nevertheless, in some situations such as when the recruitment is extremely challenging for a rare disease, the panelists concluded that the use of a non-concurrent control can be justified.

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