Kabbani Danya, Akika Reem, Wahid Ahmed, Daly Ann K, Cascorbi Ingolf, Zgheib Nathalie Khoueiry
Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
Front Pharmacol. 2023 May 18;14:1189976. doi: 10.3389/fphar.2023.1189976. eCollection 2023.
Considerable efforts have been exerted to implement Pharmacogenomics (PGx), the study of interindividual variations in DNA sequence related to drug response, into routine clinical practice. In this article, we first briefly describe PGx and its role in improving treatment outcomes. We then propose an approach to initiate clinical PGx in the hospital setting. One should first evaluate the available PGx evidence, review the most relevant drugs, and narrow down to the most actionable drug-gene pairs and related variant alleles. This is done based on data curated and evaluated by experts such as the pharmacogenomics knowledge implementation (PharmGKB) and the Clinical Pharmacogenetics Implementation Consortium (CPIC), as well as drug regulatory authorities such as the US Food and Drug Administration (FDA) and European Medicinal Agency (EMA). The next step is to differentiate reactive point of care from preemptive testing and decide on the genotyping strategy being a candidate or panel testing, each of which has its pros and cons, then work out the best way to interpret and report PGx test results with the option of integration into electronic health records and clinical decision support systems. After test authorization or testing requirements by the government or drug regulators, putting the plan into action involves several stakeholders, with the hospital leadership supporting the process and communicating with payers, the pharmacy and therapeutics committee leading the process in collaboration with the hospital laboratory and information technology department, and healthcare providers (HCPs) ordering the test, understanding the results, making the appropriate therapeutic decisions, and explaining them to the patient. We conclude by recommending some strategies to further advance the implementation of PGx in practice, such as the need to educate HCPs and patients, and to push for more tests' reimbursement. We also guide the reader to available PGx resources and examples of PGx implementation programs and initiatives.
人们已经付出了巨大努力,将药物基因组学(PGx,即研究与药物反应相关的个体间DNA序列变异的学科)应用于常规临床实践。在本文中,我们首先简要描述PGx及其在改善治疗效果方面的作用。然后,我们提出一种在医院环境中启动临床PGx的方法。首先,应该评估现有的PGx证据,审查最相关的药物,并缩小到最可操作的药物-基因对和相关变异等位基因。这是根据药物基因组学知识实施(PharmGKB)和临床药物遗传学实施联盟(CPIC)等专家策划和评估的数据,以及美国食品药品监督管理局(FDA)和欧洲药品管理局(EMA)等药物监管机构的数据来完成的。下一步是区分即时护理的反应性检测和前瞻性检测,并决定采用候选基因检测或基因panel检测的基因分型策略,每种策略都有其优缺点,然后制定出解释和报告PGx检测结果的最佳方法,并选择将其整合到电子健康记录和临床决策支持系统中。在获得政府或药物监管机构的检测授权或检测要求后,将该计划付诸实施涉及多个利益相关者,医院领导层支持该过程并与支付方沟通,药学与治疗学委员会与医院实验室和信息技术部门合作领导该过程,医疗保健提供者(HCPs)订购检测、理解结果、做出适当的治疗决策并向患者解释。我们最后建议了一些在实践中进一步推进PGx实施的策略,例如需要对HCPs和患者进行教育,并推动更多检测的报销。我们还为读者提供了可用的PGx资源以及PGx实施计划和举措的示例。