Innovations are urgently required for clinical development of antibacterials against multidrug-resistant organisms. Therefore, a European, public-private working group (STAT-Net; part of Combatting Bacterial Resistance in Europe [COMBACTE]), has reviewed and tested several innovative trials designs and analytical methods for randomized clinical trials, which has resulted in 8 recommendations. The first 3 focus on pharmacokinetic and pharmacodynamic modeling, emphasizing the pertinence of population-based pharmacokinetic models, regulatory procedures for the reassessment of old antibiotics, and rigorous quality improvement. Recommendations 4 and 5 address the need for more sensitive primary end points through the use of rank-based or time-dependent composite end points. Recommendation 6 relates to the applicability of hierarchical nested-trial designs, and the last 2 recommendations propose the incorporation of historical or concomitant trial data through Bayesian methods and/or platform trials. Although not all of these recommendations are directly applicable, they provide a solid, evidence-based approach to develop new, and established, antibacterials and address this public health challenge.

中文翻译：

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优化针对多药耐药生物的抗菌素临床试验的设计和分析：COMBACTE STAT-Net的白皮书

临床上迫切需要创新，以开发出对多药耐药生物的抗菌剂。因此，欧洲的一个公共-私营工作组（STAT-Net；欧洲抵抗细菌耐药性[COMBACTE]的一部分）审查并测试了几种创新的临床试验设计和随机临床试验的分析方法，得出了8条建议。前3个重点在于药代动力学和药效学建模，强调基于人群的药代动力学模型的相关性，对旧抗生素进行重新评估的监管程序以及严格的质量改进。建议4和5通过使用基于等级或与时间相关的复合终点来解决对更敏感的主要终点的需求。建议6与分层嵌套试验设计的适用性有关，最后2条建议建议通过贝叶斯方法和/或平台试验结合历史或伴随试验数据。尽管并非所有这些建议都直接适用，但它们提供了坚实的，循证的方法来开发新的和确定的抗菌剂并应对这一公共卫生挑战。