多区域或单国家临床试验的国际肿瘤学药物批准：一项系统评价。
International oncology drug approvals for multiregional or single-country clinical trials: A systematic review.
作者信息
Zhang Min, Onakpoya Igho, Rupalla Katrin
机构信息
Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.
Ymmunobio AG, Basel, Switzerland.
出版信息
Front Med (Lausanne). 2022 Dec 15;9:1084980. doi: 10.3389/fmed.2022.1084980. eCollection 2022.
BACKGROUND
Cancer remains one of the most common causes of morbidity and mortality worldwide. Multiregional (MRCTs) and single-country clinical trials are two common approaches to support new oncology drug approvals internationally. However, systematic reviews comparing MRCTs with single-country trials for international oncology drug approval are lacking.
METHODS
We searched health agency websites to retrieve all approved oncology drugs from 2010 to 2022. ClinicalTrials.gov was used to retrieve all pivotal study information. We used an adapted version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2) and Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) checklist to assess the risk-of-bias in randomized and non-randomized trials, respectively.
RESULTS
A total of 48 new drugs and biologics (comprising 215 pivotal clinical trials) with initial marketing approval in the United States, European Union, Japan, and China were included. The reporting quality of MRCTs vs. single-country studies was similar. The median time interval for approval was significantly longer for MRCTs than for single-country bridging studies (1,399 vs. 975 days, < 0.0001), whereas the median time interval for approval was shorter for MRCTs than for single-country standalone studies. The time gap for oncology drugs approved before 2015 was significantly longer than for those approved after 2015. The median timeline for approval in MRCTs involving 3 regions showed the shortest time-to-approval compared with MRCTs involving 4-5 and 1-2 regions. There was no significant difference in the time-to-approval among different tumor types and product types.
CONCLUSION
The median time-to-approval of MRCTs was significantly longer than that of single-country bridging studies but shorter than that of single-country standalone studies, primarily involving 3 regions as the most frequent pattern and the shortest time-to-approval to operate MRCTs as a pivotal trial. Single-country bridging studies still provide essential supplements for international oncology drug approvals if MRCTs do not apply. Future studies should explore how to shorten the time-to-approval for MRCTs.
SYSTEMATIC REVIEW REGISTRATION
[https://www.researchregistry.com/browsethe-registry#registryofsystematicreviewsmeta-analyses/], identifier [1390].
背景
癌症仍然是全球发病和死亡的最常见原因之一。多区域临床试验（MRCTs）和单国家临床试验是支持国际肿瘤药物获批的两种常见方法。然而，缺乏比较MRCTs与单国家试验用于国际肿瘤药物获批的系统评价。
方法
我们检索了卫生机构网站，以获取2010年至2022年所有获批的肿瘤药物。使用ClinicalTrials.gov检索所有关键研究信息。我们分别使用Cochrane随机试验偏倚风险工具第2版（RoB 2）和非随机干预性研究中的偏倚风险（ROBINS-I）清单来评估随机试验和非随机试验中的偏倚风险。
结果
共纳入了48种在美国、欧盟、日本和中国首次获得上市批准的新药和生物制品（包括215项关键临床试验）。MRCTs与单国家研究的报告质量相似。MRCTs的批准中位时间间隔显著长于单国家桥接研究（1399天对975天，<0.0001），而MRCTs的批准中位时间间隔短于单国家独立研究。2015年前获批的肿瘤药物的时间间隔显著长于2015年后获批的药物。与涉及4 - 5个区域和1 - 2个区域的MRCTs相比，涉及3个区域的MRCTs的批准中位时间线显示出最短的获批时间。不同肿瘤类型和产品类型之间的获批时间没有显著差异。
结论
MRCTs的批准中位时间显著长于单国家桥接研究，但短于单国家独立研究，主要涉及3个区域作为最常见模式，且作为关键试验进行MRCTs的获批时间最短。如果不适用MRCTs，单国家桥接研究仍然为国际肿瘤药物获批提供重要补充。未来的研究应探索如何缩短MRCTs的获批时间。
系统评价注册
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