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Pharmacogenomics
Pharmacogenomics
• 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
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
Hooked On Drugs...
• Brand name drugs have increased 10.5 since 2000
• “Cradle To The Grave” featured in the British Museum
www.cradletograve.org
Drug Efficacy is Questioned....
Non-Responders...
Modern Day Practice
NO EFFECTNO EFFECT
TOXICITYTOXICITY
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
The Costs Of ADR’s
• 15 billion dollars in the US alone yearly
• 1 million hospitalized in the US each year
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
Feeling Left Out?
• Are non-responders important?
• Are toxic responders important?
• Who should our priorities be focused on?
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
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.
Single Nucleotide Polymorphisms
• 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.
Research Issues
EconomicResearch Clinical Social
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
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
Clinical Issues
EconomicResearch Clinical Social
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?
Clinical Issues
• Create a file
• Manage these files
• Protect the integrity of the information within these files
• Current health status
• Family history
• Pharmacogenomics file
Social Issues and Impact
EconomicResearch Clinical Social
Social Issues and Impact
• Insurance
• Jobs
• Educational opportunities
Social Issues and Impact
• 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
Economic Issues
EconomicClinicalResearch Social
Economic Issues
• Pharmacogenomics testing
• Unnecessary preventative interventions
• Impact of healthier, aging population on economy
PharmacogenomicsGood or Bad
GOOD BAD
• 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