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PERSONALIZED MEDICINE PRECISION MEDICINE https://www.nih.gov/precision-medicine-initiative-cohort-program Graphic generated with data obtained from https://www.genome.gov/ & https://www.nih.gov/precision-medicine-initiative-cohort-program a near-term focus on cancers https://www.whitehouse.gov/ https://www.nih.gov/precision-medicine-initiative-cohort-program https://www.nih.gov/precision-medicine-initiative-cohort-program • Define precision medicine • Recap the state of affairs of precision medicine initiatives • To identify ways in which precision medicine may influence clinical practice through a case-based example, specifically focusing on: • Pharmacogenomics • Motivating behavioral changes • To acknowledge the challenges and limitations of these initiatives www.uptodate.com www.uptodate.com www.23andme.com www.uptodate.com Berger et al 2009 The epigenetic pathway. Shelley L. Berger et al. Genes Dev. 2009;23:781-783 Copyright © 2009 by Cold Spring Harbor Laboratory Press • Define precision medicine • Recap the state of affairs of precision medicine initiatives • Introduce the role of ‘Omics’ sciences in personalizing medicine • To identify ways in which precision medicine may influence clinical practice through a case-based example, specifically focusing on: • Pharmacogenomics • Motivating behavioral changes • To acknowledge the challenges and limitations of these initiatives 1. Pharmacogenomics • Improve dosing • Enhance effectiveness The Case of Warfarin dosing http://www.warfarindosing.org/Source/Home.aspx Pirmohamed et al (2013) Pirmohamed et al (2013) Genotype-Guided vs Clinical Dosing of Warfarin and Its Analogues: Meta-analysis of Randomized Clinical Trials % of time INR in therapeutic range INR >4 Major bleeding Thromboembolic events JAMA Intern Med. 2014;174(8):1330-1338. doi:10.1001/jamainternmed.2014.2368 Genotype-Guided vs Clinical Dosing of Warfarin and Its Analogues: Meta-analysis of Randomized Clinical Trials The Case of Warfarin • Smoking cessation 1. Pharmacogenomics: • Improve dosing • Enhance effectiveness Schork 2015 1. Pharmacogenomics: Drug effectiveness Chen et al. 2014 David SP 2014 2. Motivating behavior change by incorporating genetic risk into counseling 2. Motivating behavior change by incorporating genetic risk into counseling Carpenter et al. 2007; Graves et al 2014 2. Motivating behavior change by incorporating genetic risk into counseling Hollands et al 2016 Hollands et al 2016 Hollands et al 2016 Hollands et al 2016 • Pharmacogenomics • • • • Increased drug efficacy Decreased toxicity Decreased exposure to ineffective drugs Targeted therapy development • Targeting of behavioral modifications based on individual risk factors • Improved counseling and decision making Collins & Varmus 2015 http://doi.org/10.1101/gad.1787609 http://www.nejm.org/doi/full/10.1056/NEJMp1500523 • David, SP. Addiction. www.uptodate.com http://doi.org/10.1038/520609a http://www.hhs.gov/ohrp/humansubjects/commonrule/ https://www.whitehouse.gov/the-press-office/2015/01/30/fact-sheetpresident-obama-s-precision-medicine-initiative 2. Improved decision making 2. Improved decision making 2. Improved decision making
