1. Pharmacogenomics

2. Developing drugs on the basis of individual genetic differences Tailoring therapies to genetically similar subpopulations results in improved efficacy and less toxicity Pharmacogenomics = Pharmacology + Genomics

3. Hooked On Drugs... 14,000 new prescription drugs each year 30,000 new over the counter drugs each year 70 billion dollars go into drug research every year in the USA

4. Brand name drugs have increased 10.5 since 2000 “Cradle To The Grave” featured in the British Museum www.cradletograve.org

5. Drug Efficacy is Questioned....

6. Non-Responders...

7. Modern Day Practice NO EFFECT NO EFFECT TOXICITY TOXICITY TOO MUCH! decrease dose TOO MUCH! decrease dose TOO LITTLE! increase dose TOO LITTLE! increase dose TOXICITY! change drugs TOXICITY! change drugs NO EFFECT! increase dose or change drug NO EFFECT! increase dose or change drug

8. The Costs Of ADR’s 15 billion dollars in the US alone yearly 1 million hospitalized in the US each year

9. The Cost Of ADR’s 6.5% of hospital admissions are directly from ADR In the Canada 4% of hospital bed occupancy are ADR 50,000 - 100,000 toxicity related death per year in the USA

10. Feeling Left Out? Are non-responders important? Are toxic responders important? Who should our priorities be focused on?

11. Pharmacogenomics The study of genome-derived data to predict a body’s response to a drug or susceptibility to a disease: Human genetic variation in DNA –-–- Single nucleotide polymorphisms (SNPs) –-–- Copy number differences –-–- Insertions –-–- Deletions –-–- Duplications –-–- Rearrangements RNA and protein expression differences

12. Single Nucleotide Polymorphisms Occur when a single nucleotide (A,T,C or G) in the genome sequence is altered. Comprise 90% of all human genetic variation Exist every 100 to 300 bases along the 3 billion base human genome.

13. Usually have no effect on cell function, but some could predispose people to disease or influence their response to a drug 10 million SNP’s are known Found in both coding (i.e., gene) and noncoding regions of the genome.

14. Research Issues EconomicResearchClinicalSocial

15. Research Issues Deciding on a Research Focus: Single gene (i.e., easier to treat) Polygenic diseases and/or disorders (i.e., harder to treat) Consequence: Potential to develop drugs for a specific genotype that are harmful to other genotypes

16. Research Issues Narrower target population could exclude those who might also benefit from therapies Evaluating therapies in smaller, targeted trials might miss critical, albeit rare, adverse drug events Translating

17. Clinical Issues EconomicResearchClinicalSocial

18. Clinical Issues Who should be offered testing? What training or certification should be required to administer, interpret and explain tests? How should tests be integrated into the current standard of care?

19. Create a file Manage these files Protect the integrity of the information within these files Current health status Family history Pharmacogenomics file

20. Social Issues and Impact EconomicResearchClinicalSocial

21. Social Issues and Impact Insurance Jobs Educational opportunities

22. Will I develop this disease ten years from now? Do I want to know my susceptibility to this incurable disease? Can I indulge in unhealthy habits? Health Horoscope

23. Economic Issues Economic ClinicalResearchSocial

24. Economic Issues Pharmacogenomics testing Unnecessary preventative interventions Impact of healthier, aging population on economy

25. Pharmacogenomics Good or Bad GOODBAD Accelerated drug development Simplified clinical trials Reduced adverse events Powerful, customized drugs Effective disease prevent strategies New opportunities for discrimination Eroding privacy and confidentiality Increasing cost of heath care