The organisation and diffusion of translational research: Can cardiovascular medicine learn from oncology? Case studies of pharmacogenomics in the NHS

该项目旨在了解影响NHS心血管实践采用PGt/x的关键因素。心血管疾病（cvd）是英国最常见的死亡原因，许多重要的心血管药物具有PGt/x适应症，可用于个性化治疗，使其通过优化剂量更有效，减少药物不良反应，总体上为患者提供更好的护理，为NHS带来显著回报。我们是否可以从肿瘤学中学习PGt/x知识在临床实践中已经处于相对先进的实施阶段？我们将解开制度和组织安排，以确定有利于在心血管医学中应用PGt/x和个性化方法的创新管理实践。该研究的重点是PGt/x知识在NHS的背景化。研究表明，尽管英国在从基础科学到人类研究的早期研究方面投入了大量资金，但在临床和健康决策中对新知识的转化和实施投入的努力和投资却很少。因此，我们的贡献旨在了解机构，组织和创新管理问题，推动和/或阻碍先进的PGt/x和临床知识的转化，以个性化的方法治疗心脏和循环系统疾病。为此，本研究将深入探讨NHS专业人员的行为如何制度化。这意味着理解新的常规如何出现的社会技术层面，组织如何创新以及如何管理这种变化过程（医疗创新），以将PGt/x知识引入NHS心血管病房。我们利用肿瘤学和个性化癌症治疗的持续进展来反思影响CVD领域PGt/x知识实施的支持/抑制因素。该项目利用了一个强大的多学科团队，包括复杂性和医学创新学者，药物遗传学研究及其在医疗实践中的应用的先驱，肿瘤学和心血管临床医生。该研究计划包括四个阶段，将在36个月内进行。阶段1)包括绘制关于PGt/x -药物关联的现有知识，并对文献进行回顾。这些将用于绘制在实践中实现PGt/x知识的潜在因素的类型。第二阶段和第三阶段将分别开展肿瘤和心血管药物的案例研究。这一选择背后的理由是由于PGt/x在两个医疗领域的不同渗透。阶段4)应包括系统的比较分析、初步报告、验证和与更广泛的医学和社会科学学科学术界、患者倡导团体和政策制定者的接触。该研究将在NHS的一些活跃临床单位内进行，这些单位被确定为临床实践中PGt/x的早期采用者。所开发的方法将有助于促进我们对在心脏病学中实施PGt/x的一般原则的理解，并将社会技术重点放在必要的技术、组织内的制度和行为改变上。这些可以被广泛地视为创新管理步骤，首先确定对实施、测试/护理具有关键作用的利益相关者，并对心血管医学中PGt/x指南的实施产生实际影响。该项目将受益于由学者、一名临床医生和一名患者代表组成的咨询委员会的监督和指导。em . Stan Metcalfe教授（UoM）， Alex Faulkner教授（Sussex）， Ellen Moors教授（乌得勒支），William Newman教授（NW -基因组医学服务联盟），Ann Bamford教授（GM -卒中综合治疗网络）。

This project sets out to understand the critical factors affecting the adoption of PGt/x in NHS cardiovascular practices. Cardiovascular diseases (CVDs) are the most common causes of mortality in the UK and a number of important cardiovascular drugs have PGt/x indications that may be employed to personalise therapies making them more effective by optimising dosages, reducing adverse drug reactions and overall providing better care for patients with significant returns for the NHS. Can we learn from oncology where PGt/x knowledge is already at a relatively advanced stage of implementation in clinical practice? We shall unpack institutional and organisational arrangements to identify innovation management practices that favour the application of PGt/x and personalised approaches in cardiovascular medicine.The focus of the study is the contextualisation of PGt/x knowledge in the NHS. Studies have shown that while there has been tremendous investment in early-stage research from basic science to human studies in the UK, less effort and investments have been given to the translation and implementation of new knowledge in clinical and health decision making. Thus, our contribution aims at understanding the institutional, organisational and innovation management issues driving and/or hindering translation of advanced PGt/x and clinical knowledge in a personalised approach to heart and circulatory diseases. To this end, this research will deep-dive into how the behaviour of NHS professionals become institutionalised. This means understanding the socio-technical dimensions of how new routines emerge, how organisations innovate and how this change process (medical innovation) is managed to introduce PGt/x knowledge on the cardiovascular wards of the NHS. We use the ongoing progress in oncology and personalised cancer therapy to reflect upon the supporting/inhibiting factors affecting the implementation of PGt/x knowledge in the CVD domain. The project capitalises on a strong multidisciplinary team incorporating complexity and medical innovation scholars, pioneers in pharmacogenetic research and its applications in medical practice, oncology and cardiovascular clinicians.The research plan comprises 4 phases to be carried out over 36 months. Phase 1) consists in mapping the knowledge available on PGt/x - drug associations and conduct a review of the literature. These will be used to draw a typology of factors underlying the implementation of PGt/x knowledge in practice. Phase 2) and Phase 3) will develop cases studies in oncology and cardiovascular medicines respectively. The rationale behind this choice is due to the diverse penetration of PGt/x within the two medical fields. Phase 4) shall comprise the systematic comparative analysis, the preliminary report, validation and engagement with the wider academic communities in medical and social science disciplines, patient advocacy groups and policy makers.The study will be conducted within a number of active clinical units in the NHS identified as early adopters of PGt/x in clinical practice. The methodology developed will contribute to advancing our understanding of the general principles to implementing PGt/x in cardiology with a socio-technical focus on the necessary technologies, institutional and behavioural changes within the organisation. These can be broadly seen as innovation management steps beginning with the identification of stakeholders who are key to implementation, testing/care with practical repercussions on the implementation of PGt/x guidelines in cardiovascular medicine.The project will benefit from oversight and guidance of an advisory board comprising academics, a clinician and a patient representative. Em.Prof Stan Metcalfe (UoM), Prof Alex Faulkner (Sussex), Prof Ellen Moors (Utrecht), Prof William Newman (NW - Genomic Medicine Service Alliance), Ann Bamford (GM - Integrated Stroke Delivery Network).