Centre for Drug Safety Science (CDSS)

药物作为药物的使用对人类健康作出了巨大贡献，药物发现过程针对人类疾病的大多数方面。然而，所有药物都与副作用或药物不良反应（adr）有关，其频率和严重程度因药物和患者群体而异。NHS和行业的总体负担都很大。我们已经表明，至少6.5%的成人住院是由于不良反应，大约15%的住院患者在住院期间遭受不良反应。据推测，在全国范围内，药品不良反应每年给英国国民医疗服务体系造成的损失超过6.37亿英镑，或每年每张病床约5000英镑。这是一个保守的估计，可能要高得多。我们在英国的研究结果在许多国家都得到了证实，表明药物不良反应是一个全球性的健康问题。不良反应可导致停药或限制用药，即使不良反应仅发生在少数患者中。这可能会阻碍医生为大多数受益于药物而没有出现不良反应的患者使用其他有效药物。整个药物安全问题也对制药行业的盈利能力产生重大影响，从而影响英国的经济。MRC药物安全科学中心（CDSS）因此于2008年成立，作为利物浦大学（UoL）和曼彻斯特大学（UoM）之间的合作，以响应建立国家中心调查adr机制的需求。CDSS已经建立了一个基础设施，允许临床前和临床科学家使用尖端技术并肩工作，分析定义良好的临床样本。我们对药物性肝损伤和药物性超敏反应机制的理解取得了进展，包括确定遗传易感因素和改进诊断测试的发展。在接下来的5年里，我们的创新发现将转化为更好的患者临床护理，改善制药行业的药物开发，并为监管机构提供更好的信息。此外，我们的基础设施将扩展到评估与肾脏、胃肠道和心血管系统相关的药物副作用。总的来说，CDSS及其合作者的研究结果将更好地了解不良反应的风险并改善患者的预后。我们将继续以非竞争的方式与制药行业的科学家和监管机构密切合作，这将使我们能够获得公司特定的药物和患者样本，为我们提供解决全行业药物安全挑战的工具。与此同时，我们将作为一个论坛，与所有药物安全科学专业人员（无论是学术界、卫生保健提供者、工业界还是监管机构）进行培训和知识交流，这将通过我们扩大的非临床和临床科学家培训计划得到显著加强。这将使我们能够为所有相关利益相关者提高英国药物安全科学的能力。我们将继续在各个层面开展患者和公众参与活动，以确保我们的目标和目标得到完善，使患者成为中心研究和培训活动的中心焦点。因此，该中心的新使命宣言是“利用我们在中心积累的药物安全科学的临界质量和知识，开展前沿科学，培养下一代药物安全科学家，了解临床重要和当前相关的药物不良反应的基本机制，以制定策略，提高现有药物和新药的收益-风险比，造福患者；行业和监管机构。”

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 side effects or adverse drug reactions (ADRs) which vary in frequency and severity dependent on the drug and patient population. The overall burden is large to both the NHS and Industry.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.ADRs can lead to withdrawal or restricted use of drugs, even if the ADR occurs in only a minority of patients. This can impede the use of otherwise effective drugs being prescribed by physicians for the majority of patients who benefit from the drug without developing ADRs. The whole issue of drug safety also has a major impact on the profitability of the pharmaceutical industry, and thus the economy of the UK.The MRC Centre for Drug Safety Science (CDSS) was therefore created in 2008 as a collaboration between the Universities of Liverpool (UoL) and Manchester (UoM) in response to a perceived need to establish a National Centre to investigate mechanisms of ADRs. An infrastructure that allows pre-clinical and clinical scientists to work side-by-side using cutting-edge technologies to analyse well-defined clinical samples has been created in CDSS. Progress has been made in our understanding of the mechanisms of drug-induced liver injury and drug-induced hypersensitivity, including the identification of genetic predisposing factors and the development of improved diagnostic tests. Over the next 5 years our innovative findings will be translated into better clinical care for patients, improved drug development for Pharmaceutical Industry and better information for Regulators. Furthermore, our infrastructure will be extended to evaluate drug side effects associated with the kidney, the gastrointestinal tract and the cardiovascular system. Collectively, the findings from the CDSS and its collaborators will provide a better understanding of risk of ADRs and improve patient outcomes. We will continue to work closely with scientists from the pharmaceutical industry and from regulatory authorities in a non-competitive manner that will allow us to access company-specific drugs and patient samples which provide us with the tools to address industry-wide drug safety challenges. At the same time we will act as a forum for training and knowledge exchange with all drug safety science professionals (be they in academia, health care providers, industry or regulatory authorities) which will be significantly enhanced by our expanded training programme for non-clinical and clinical scientists. This will allow us to improve capacity in drug safety science in the UK for all relevant stakeholders. We will continue our patient and public engagement activities at all levels in order to ensure that our aims and objectives are refined to make patients a central focus of the research and training activities in the Centre.Thus the new mission statement for the Centre is "to use the critical mass and knowledge in drug safety science that we have now accrued within the Centre to undertake leading edge science, and train the next generation of drug safety scientists, to understand the fundamental mechanisms of clinically important and currently relevant adverse drug reactions in order to develop strategies to improve the benefit-risk ratio of current and new medicines, for the benefit of patients, industry and regulators."