Non-adherence to treatment: a methodological approach to compensating for its impact in chronic infections, using tuberculosis as a model disease.

对慢性(即长期)疾病设计不完善的治疗方案会导致持续的、可能恶化的症状。当一种疾病可以在人与人之间传播时，我们还会面临发展和传播抗药性的风险，这是指细菌或病毒由于基因变化而变得无法用正常药物治疗。这既危及个人健康，也危及人口健康。如果一个人不完全坚持他们的治疗(没有按照建议服用所有的药物)，这可能会导致同样的问题，但由于药物的不同性质，其影响取决于所使用的药物。坚持治疗不力每年在全球造成数千亿美元的损失。对于许多慢性病，我们不知道患者不服用多少药物才是安全的，但仍然可以治愈。在整个治疗过程中，每10剂中至少服用8剂通常被认为是重要的，但这缺乏充分的证据，而且非常简单，特别是考虑到不同疾病的药物有很大不同。这项研究旨在使用不同的方法和真实、详细的依从性和治疗结果数据来确定正常的患者行为应该如何影响我们的治疗方法。结核病(TB)之所以被选为模式疾病，是因为它具有全球重要性(2015年新增患者1040万人，相关死亡140万人)，而且需要更好的治疗。目标是：1)描述在日常治疗的六个月中，依从性差的情况、时间和原因，以及依从性如何与不同地点的治疗结果相关。2)确定依从性模式如何影响随着时间的推移耐药性的发展。3)采用理论模型来检验依从性对最佳治疗方式(如缓释片)的影响。4)收集这些证据，以确定依从性如何改变我们的治疗方法，以及如何设计新的方案。这项工作不仅将指导全球治疗结核病的最佳方式，但所使用的方法也将有助于解释常见的依从性模式应该如何影响现实世界中其他情况下的药物使用。最好的给结核病药物的方法可以被包括在新的临床试验中，以改善对患者的卫生服务，并使其物有所值。撰写临床指南的人将药物试验数据解释为反映现实生活的方式将得到改进。这些发现还可以为促进依从性的工具的试验提供依据。

Imperfectly designed treatment regimens for chronic (i.e. long-lasting) diseases result in continued, and possibly worsened, symptoms. When a disease can be passed from person-to-person we additionally risk the development and spread of drug resistance, which is when a bacterium or virus becomes untreatable by normal medicines as it has genetically changed. This endangers both individual- and population-level health. If someone incompletely 'adheres' to their treatment (does not take all their medicine as recommended) this can result in the same problems, but the impact of this depends on the drugs being used, due to their differing properties. Poor adherence to treatment costs hundreds of billions of dollars globally each year.For many chronic diseases, we do not know how much medicine it is safe for patients not to take and still be cured. Taking at least eight of every 10 doses across the entire length of treatment is often said to be important, but this lacks good evidence and is highly simplistic, especially given how much drugs vary from disease to disease.This study aims to use different methodologies and real-life, detailed, adherence and treatment outcome data to decide how normal patient behaviour should influence our approach to treatment. Tuberculosis (TB) has been chosen as a model disease due to its global importance (10.4 million new patients, 1.4 million related deaths in 2015) and the need for better treatments. The Objectives are:1) Describe how, when and why poor adherence occurs during the six months of daily treatment, and how adherence is related to the outcome of treatment across different places.2) Determine how adherence patterns influence the development of drug resistance over time.3) Adapt a theoretical model to examine the impact of adherence on the best way to give treatment (e.g. slow release tablets).4) Draw together these strands of evidence to determine how adherence should alter our approach to treatment and how new regimens should be designed.This work will not only guide the best way of treating TB globally, but the methods used will also help to interpret how common adherence patterns should influence the use of drugs for other conditions in the real world. The best ways of dosing TB drugs can be included in new clinical trials to improve health services for patients and value for money. The way in which drug trial data is interpreted as reflecting real life by the people writing clinical guidance will be refined. The findings can also inform trials of tools to promote adherence.