Centre for Drug Safety Science (CDSS)

药物安全科学中心 (CDSS)

• 批准号: MR/L006758/1
• 负责人: Munir Pirmohamed
• 金额: $ 391.56万
• 依托单位: University of Liverpool
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FL006758%2F1
• 关键词: Centre; Drug; Safety; Science; CDSS

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."

药物作为药物的使用为人类健康做出了巨大贡献，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) 相关，其发生频率和严重程度取决于药物和患者群体。对于 NHS 和行业来说，总体负担都很大。我们已经表明，至少 6.5% 的成人入院是由于 ADR 造成的，大约 15% 的住院患者在住院期间会遭受 ADR 的困扰。据认为，在全国范围内，ADR 每年给英格兰 NHS 造成的损失超过 6.37 亿英镑，即每张病床每年大约花费 5000 英镑。这是一个保守的估计，并且可能要高得多。我们在英国的研究结果已在许多国家得到复制，表明药品不良反应是一个全球性的健康问题。药品不良反应可能导致停药或限制使用药物，即使药品不良反应仅发生在少数患者身上。这可能会妨碍大多数患者使用医生开出的其他有效药物，这些患者从该药物中受益而不会出现不良反应。整个药物安全问题也对制药行业的盈利能力以及英国的经济产生重大影响。因此，利物浦大学 (UoL) 和曼彻斯特大学 (UoM) 于 2008 年合作创建了 MRC 药物安全科学中心 (CDSS)，以满足建立国家中心来研究 ADR 机制的需要。 CDSS 中创建了一个基础设施，允许临床前和临床科学家使用尖端技术并肩工作来分析明确的临床样本。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，包括遗传诱发因素的识别和改进的诊断测试的开发。未来 5 年，我们的创新发现将转化为更好的患者临床护理、改进的制药行业药物开发以及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有助于更好地了解 ADR 风险并改善患者治疗结果。我们将继续以非竞争的方式与制药行业和监管机构的科学家密切合作，这将使我们能够获得公司特定的药物和患者样本，从而为我们提供解决全行业药物安全挑战的工具。同时，我们将充当所有药物安全科学专业人员（无论是学术界、医疗保健提供者、行业还是监管机构）的培训和知识交流论坛，这将通过我们针对非临床和临床科学家的扩大培训计划而得到显着增强。这将使我们能够提高英国所有相关利益相关者的药物安全科学能力。我们将继续在各级开展患者和公众参与活动，以确保完善我们的宗旨和目标，使患者成为中心研究和培训活动的中心焦点。因此，中心的新使命宣言是“利用我们在中心内积累的药物安全科学的临界质量和知识来开展前沿科学，并培训下一代药物安全科学家，了解临床上重要的和当前相关的药物不良反应的基本机制，以便 制定策略来提高现有药物和新药物的效益风险比，以造福于患者、行业和监管机构。”

项目成果

UHRF1 regulation of the Keap1-Nrf2 pathway in pancreatic cancer contributes to oncogenesis.

• DOI: 10.1002/path.4665
• 发表时间: 2016-02
• 期刊: The Journal of pathology
• 作者: Abu-Alainin W;Gana T;Liloglou T;Olayanju A;Barrera LN;Ferguson R;Campbell F;Andrews T;Goldring C;Kitteringham N;Park BK;Nedjadi T;Schmid MC;Slupsky JR;Greenhalf W;Neoptolemos JP;Costello E
• 通讯作者: Costello E

Medical and Health Genomics

医疗与健康基因组学

• DOI: 10.1016/b978-0-12-420196-5.00010-1
• 发表时间: 2016
• 作者: Alfirevic A

Renal function monitoring in heart failure - what is the optimal frequency? A narrative review.

• DOI: 10.1111/bcp.13434
• 发表时间: 2018-01
• 期刊: British journal of clinical pharmacology
• 影响因子: 3.4
• 作者: Al-Naher A;Wright D;Devonald MAJ;Pirmohamed M
• 通讯作者: Pirmohamed M

Phenotype standardization for statin-induced myotoxicity.

• DOI: 10.1038/clpt.2014.121
• 发表时间: 2014-10
• 期刊: Clinical pharmacology and therapeutics
• 影响因子: 6.7

Genetic testing for prevention of severe drug-induced skin rash.

基因检测可预防严重药物引起的皮疹。

• DOI: 10.1002/14651858.cd010891.pub2
• 发表时间: 2019
• 期刊: The Cochrane database of systematic reviews
• 作者: Alfirevic A