Tom A Yates, Samara Barnes, Martin Dedicoat, Onn Min Kon, Heinke Kunst, Marc Lipman, Kerry A Millington, Andrew J Nunn, Patrick Pj Phillips, Jessica L Potter, S Bertel Squire
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引用次数: 0
摘要
大多数耐药性结核病的 III 期试验要么没有足够的能力量化微生物终点的差异,要么需要长达十年的时间才能完成。以治疗中断和治疗方案改变差异为主的综合主要终点可能会掩盖治疗失败和复发方面的重要差异。尽管治疗耐药性结核病的新方案似乎非常有效,但对新药的耐药性正在迅速出现。我们需要更短、更安全、更耐受的治疗方案,包括那些对贝达喹啉耐药结核病有效的治疗方案。从多个治疗方案 A 与治疗方案 B 的对比试验过渡到单一的大型 III 期平台试验,将加快获得对相对疗效和安全性的可靠估计。采用现代适应性平台设计可进一步提高效率。试验人员、受影响社区代表、资助者和监管者之间的合作对于开发这种针对耐药结核病治疗方案的 III 期平台试验至关重要。
Drug-resistant tuberculosis treatments, the case for a phase III platform trial.
Most phase III trials in drug-resistant tuberculosis have either been underpowered to quantify differences in microbiological endpoints or have taken up to a decade to complete. Composite primary endpoints, dominated by differences in treatment discontinuation and regimen changes, may mask important differences in treatment failure and relapse. Although new regimens for drug-resistant tuberculosis appear very effective, resistance to new drugs is emerging rapidly. There is a need for shorter, safer and more tolerable regimens, including those active against bedaquiline-resistant tuberculosis. Transitioning from multiple regimen A versus regimen B trials to a single large phase III platform trial would accelerate the acquisition of robust estimates of relative efficacy and safety. Further efficiencies could be achieved by adopting modern adaptive platform designs. Collaboration among trialists, affected community representatives, funders and regulators is essential for developing such a phase III platform trial for drug-resistant tuberculosis treatment regimens.
期刊介绍:
The Bulletin of the World Health Organization
Journal Overview:
Leading public health journal
Peer-reviewed monthly journal
Special focus on developing countries
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Top public and environmental health journal
Impact factor of 6.818 (2018), according to Web of Science ranking
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Essential reading for public health decision-makers and researchers
Provides blend of research, well-informed opinion, and news