Anti-infectives Consulting, LLC, Stonington, CT, USA.
Curr Opin Pharmacol. 2012 Oct;12(5):522-6. doi: 10.1016/j.coph.2012.06.010. Epub 2012 Jul 24.
In order to meet the challenges of our current medical need to address infections caused by highly resistant pathogens, we propose the use of superiority trial designs. The proposed trials may or may not be statistically powered. All require extensive preclinical justification. The designs could use either historical or active controls. For historically controlled trials we propose two approaches for defining the control response rate to therapy; (1) the use of pharmacometrics from modern trials and (2) the use of a concurrent observational study. Designs for active controlled trials could be (1) standard of care+test vs. standard of care alone or (2) standard of care vs. test article. The second approach requires extensive justification to show that the test article will be of sufficient efficacy to allow ethical use as a single agent.
为了应对当前医学领域面临的挑战，即解决由高度耐药病原体引起的感染，我们提出使用优势试验设计。所提议的试验可能具有统计学效力，也可能不具有统计学效力。所有试验都需要广泛的临床前验证。这些设计可以使用历史对照或活性对照。对于历史对照试验，我们提出了两种定义治疗反应率的方法：（1）使用现代试验的药代动力学数据，（2）使用同期观察性研究。活性对照试验的设计可以是（1）标准治疗+试验药物与标准治疗相比，或（2）标准治疗与试验药物相比。第二种方法需要进行广泛的论证，以证明试验药物具有足够的疗效，使其可以作为单一药物进行伦理使用。
