How Genetic Variants Impact the Safety and Effectiveness of Drugs Pharmacogenetics PGXL Laboratories Every human has a genetic code that is unique to them There is no perfect version of the code; we all have variants Variances in genes responsible for drug metabolism, transport and uptake/binding can: o Be of no consequence to the drugs safety and efficacy o Render a medication useless o Result in a medication causing serious adverse reactions Pharmacogenetics The Study of How Our Genes Affect Our Response to Drugs 1.There can be wide variability in patient response to commonly prescribed medications 2.Genetics is estimated to account for 20-95% of the variability in drug effects 3.Adverse Drug Reactions (ADRs) are the 6 th leading cause of death 4.A review of drugs most commonly associated with ADRs found that 57% (16 of 27) were metabolized by a gene with a known genetic polymorphism Pharmacogenetics Why It Matters Pharmacogenetics Same Diagnosis, Same Medications, Different Outcomes No Variance Normal Response Variance Risk Decreased Variance Lack of Efficacy Variance High Risk Typical Clinic Day N=30 Incidence of Genetic Variants Important to Drug Selection and Drug Dose Gene % of Extensive Metabolizers % of Intermediate Metabolizers % of Poor Metabolizers % of Ultra-Rapid Metabolizers VARIANTS 2D653%35%10%2%47% 2C1936%32%4%28%64% 2C957%40%3%NA43% VKOR>70% 3A487%12%1%N/A13% 3A51%18%81%N/A99% SLC6A425%50%25%N/A75% 1. Pharmacogenetics Knowledge Base Implementation:Property of PGxl Laboratories 1988 International Human Genome Initiative (HGRI) launched 1989 Dr. Roland Valdes launches post-PhD Molecular Clinical Chemistry program 1993 Dr. Francis Collins assumes leadership of HGRI 1997 Dr. Valdes and Dr. Mark Linder publish seminal pharmacogenetics paper Evolution of Pharmacogenetics PG XL Founders Are Pioneers in the Field Continued 2001 PGXL Laboratories is first CLIA-certified pharmacogenetics specialist in U.S Human genome sequenced and published 2010 Drs. Valdes and Linder publish guidelines for operating a pharmacogenetics laboratory Evolution of Pharmacogenetics PG XL Founders Are Pioneers in the Field Continued State-of-the-Art Benefits of Molecular PGx Guided Therapy Decision Making Behavioral Health Treatment Resistant Depression Schizophrenia Cardiovascular Anti-Platelet Activation Anti-Coagulation Pain Management Opioids Patient Improvement Cost Savings Patient Satisfaction & Compliance Patient Satisfaction & Compliance Risk Reduction Personalized Medicine Program PM Program Core Team Creation PGxl & Client Project Planning Meeting Schedule Design Program Launch and Support Program Track and Modify Program