论文部分内容阅读
目前全世界耐多药结核病(MDR-TB)的负担正在日益加重,严重阻碍全球结核病控制工作的进度。MDR-TB的治疗是一项复杂的、长期的、昂贵的工作,并且需要合适的临床和实验室基础设施。大多数MDR-TB患者仍然不能得到正确的诊断服务或有质量保证的二线药,从而导致高发病率和高病死率。使用降低毒性的药物进行更加有效的MDR-TB治疗能够安全给予联合感染人类免疫缺陷病毒(HIV)的患者,这是一项亟待研究的重点,能够节省整个卫生系统的费用。在这种情况下,了解如何以最佳方式设计和开展能够改进MDR-TB治疗的随机对照试验是一项新的紧迫任务,可以确定现存药物和新药物的最佳组合,从而应用于有效和安全的治疗方案中,特别是疗程短的方案,那样对患者来说更容易接受并且能够安全地与抗病毒治疗联合。在本文中,出于上述目标,我们着重强调设计和实施Ⅱ期和Ⅲ期试验的方法学问题。我们建议合理选择合适的设计和结果测量工具,与新诊断技术联合使用,能够解决很多方法学和逻辑问题。这些改进是治疗MDR-TB患者,也许最终是药物敏感性结核病患者历史性改进的关键。由于合并感染HIV,在耐药患者中开展临床试验比治疗药物敏感性结核病的试验能通过一种更快更廉价的通道获得批准。
The current burden of MDR-TB in the world is increasing, seriously hampering the progress of global tuberculosis control. The treatment of MDR-TB is a complex, long-term, expensive job and requires the right clinical and laboratory infrastructure. Most MDR-TB patients still can not get the right diagnostic service or quality assured second-line drugs, resulting in high morbidity and high mortality. The use of less toxic drugs for more effective MDR-TB treatment can be safely administered to patients co-infected with human immunodeficiency virus (HIV), an urgent research topic that can save the entire health system. In this context, understanding how best to design and implement randomized controlled trials to improve MDR-TB treatment is a new and urgent task that will determine the best combination of existing and new drugs to apply to effective and Safe treatment regimens, especially short-course regimens, are more acceptable to patients and safely combined with antiviral therapy. In this article, out of these goals, we highlight the methodological issues involved in designing and implementing Phase II and III trials. We recommend that a reasonable selection of appropriate design and result measurement tools be used in conjunction with new diagnostic techniques to solve many of the methodological and logical issues. These improvements are the treatment of patients with MDR-TB, and may eventually be the key to historic improvements in patients with drug-sensitive TB. Because of co-infection with HIV, trials in drug-resistant patients than in drug-susceptible tuberculosis can be approved through a faster and cheaper channel.