MICA: Applying innovative technologies to improve benefit-risk ratio of drugs: developing a national resource underpinned by the MRC Centre for CDSS

药物作为药物的使用为人类健康作出了巨大贡献，药物发现过程涉及到人类疾病的大多数方面。然而，所有药物都与反应的可变性有关：即一些患者对药物没有反应，而另一些患者则产生副作用或药物不良反应(ADRs)。这可能与患者的因素(遗传或环境)或他们的疾病差异有关。患者对药物的反应方式不同造成的总体负担对NHS和行业来说都是巨大的。例如，在ADR方面，我们已经表明，至少6.5%的成人住院是由于ADR，大约15%的住院患者在住院期间遭受ADR。在全国范围内推算，英国NHS每年花费的ADR费用超过6.37亿GB，或每年每张医院床位约5000 GB。这是一个保守的估计，很可能要高得多。我们在英国的发现已经在许多国家得到复制，表明ADR是一个全球性的健康问题。我们的申请集中在具有国际声誉的MRC药物安全科学中心(CDSS)。病人是我们承担的工作的中心。我们已经开发了一种基础设施，允许临床前和临床科学家使用尖端技术并肩工作，分析定义明确的临床样本。在这一应用中，我们要求最先进的技术建立在这一基础设施的基础上，并在分层医学领域产生阶段性变化-即根据患者的疾病、遗传和环境因素确定最佳治疗方案。我们的目标是基于我们现有的专业知识和经验以及技术平台开发一种全面的资源，以便评估个体在药物反应中的差异，个体之间的疾病差异，以及这与临床结果的差异有何关系。我们将通过研究不同的“实验”系统来做到这一点，从试管中的单细胞到人类的实验研究，再到在临床环境中对患者的仔细临床观察。这将有助于将实验室的研究结果转化为临床护理(病床到床边)，但重要的是，在临床环境中吸取的经验教训也将在实验室进一步研究(床边到病床)，以便我们能够更多地了解疾病过程。

The use of drugs as medicines has made an enormous contribution to human health with the drug discovery process being directed to most aspects of human disease. However, all drugs are associated with variability in response: that is some patients do not respond to drugs, while others develop side effects or adverse drug reactions (ADRs). This may be related to patient factors (genetic or environmental) or differences in their disease. The overall burden caused by differences in the way patients respond to drugs is large to both the NHS and Industry. For example, with ADRs, we have shown that at least 6.5% of all adult admissions to hospitals are due to ADRs and that approximately 15% of inpatients suffer an ADR during hospitalisation. Extrapolated nationally, ADRs are thought to cost the NHS in England in excess of £637 million annually, or approximately £5000 per hospital bed per year. This is a conservative estimate and is likely to be much higher. Our findings in the UK have been replicated in many countries showing that ADRs are a global health issue.Our application focuses on the MRC Centre for Drug Safety Science (CDSS) which has an international reputation. The patient is at the centre of the work we undertake. We have developed an infrastructure that allows pre-clinical and clinical scientists to work side-by-side using cutting-edge technologies to analyse well-defined clinical samples. In this application, we request state-of-the-art technologies to build upon this infrastructure and produce a step-change in the area of stratified medicine - that is, to identify the best treatments for patients based on profiling their disease, genetic and environmental factors. Our aim is to develop a comprehensive resource, based on our existing expertise and experience and the technology platforms, to allow for assessment of how individuals vary in drug responses, how diseases differ between individuals, and how this relates to variation in clinical outcomes. We will do this through investigation of different "experimental" systems ranging from single cells in test-tubes to experimental studies in man, to careful clinical observation of patients in clinical settings. This will facilitate translation of findings in the laboratory to clinical care (bench to bedside), but importantly lessons learnt in clinical settings will also be investigated further in the laboratories (bedside to bench), so that we can learn more about disease processes.