School of General Practice and Continuing Education, Capital Medical University, Beijing, China.
Department II of Pharmaceuticals Surveillance and Evaluation, National Center for ADR monitoring, Beijing, China.
J Clin Epidemiol. 2023 May;157:74-82. doi: 10.1016/j.jclinepi.2023.03.006. Epub 2023 Mar 10.
To characterize the indications approved by the US Food and Drug Administration (FDA) on the basis of early phase clinical trials (EPCTs) and compared with that of phase three randomized controlled trials.
We collected the publicly available FDA documents of targeted anticancer drugs approved between January 2012 and December 2021.
We identified 95 targeted anticancer drugs with 188 indications approved by the FDA. One hundred and twelve (59.6%) indications were approved on the basis of EPCTs, with a significant increase of 22.2% per year. Of 112 EPCTs, 32 (28.6%) were dose-expansion cohort trials and 75 (67.0%) were single-arm phase 2 trials, respectively, with a significant increase of 29.7% and 18.7% per year. Compared with indications approved on the basis of phase three randomized controlled trials, the indications approved on the basis of EPCTs had significantly higher odds in receiving accelerated approval and lower odds in the number of entered patients of pivotal trials.
Dose-expansion cohort trials and single-arm phase 2 trials played a critical role in EPCTs. EPCT was a major trial type in providing evidences for the FDA approvals of targeted anticancer drugs.
根据早期临床试验 (EPCT) 对美国食品和药物管理局 (FDA) 批准的适应证进行特征描述，并与 III 期随机对照试验进行比较。
我们收集了 2012 年 1 月至 2021 年 12 月期间获得批准的靶向抗癌药物的公开 FDA 文件。
我们确定了 95 种获得 FDA 批准的靶向抗癌药物，共 188 种适应证。其中 112 种适应证 (59.6%) 是基于 EPCT 批准的，每年增长 22.2%。在 112 项 EPCT 中，32 项 (28.6%) 为扩展队列试验，75 项 (67.0%) 为单臂 II 期试验，分别每年增长 29.7%和 18.7%。与基于 III 期随机对照试验批准的适应证相比，基于 EPCT 批准的适应证具有更高的加速批准几率和更低的关键试验入组患者数量几率。
扩展队列试验和单臂 II 期试验在 EPCT 中发挥了关键作用。EPCT 是为 FDA 批准靶向抗癌药物提供证据的主要试验类型。
