Transcript Precision Medicine by Leland Hull

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
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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