Personalized Medicine: Balancing the Promise and Peril of Pharmacogenomics Tamara Zemlo, Ph.D., MPH Executive Director The Science Advisory Board

The Science Advisory Board Online community of life science professionals Organized by BioInformatics, LLC, a research and consulting firm in Arlington, VA Launched November 1997 Influence development of tools & technologies Communicate with colleagues on a global scale 26,000+ members

Online community of life science professionals

Organized by BioInformatics, LLC, a research and consulting firm in Arlington, VA

Launched November 1997

Influence development of tools & technologies

Communicate with colleagues on a global scale

26,000+ members

Opportunities: Information Exchange Technology Needs Product Usage Emerging Trends Best Practices New Product Availability Technology Innovations Through the Internet, The Science Advisory Board facilitates this multilayer, bilateral communication effectively and efficiently. The Science Advisory Board Blogs Forum Posts Perspectives Product Reviews In-Depth Interviews Focus Groups Instant Polls Surveys Life Science Companies Scientists

Pharmacogenomics: Perspectives from the Bench and the Bedside Study sponsored by The Science Advisory Board Provide insights into technologies, challenges and opportunities of SNP-based pharmacogenomics research Conducted in June 2005 34-question survey Over 500 respondents

Study sponsored by The Science Advisory Board

Provide insights into technologies, challenges and opportunities of SNP-based pharmacogenomics research

Conducted in June 2005

34-question survey

Over 500 respondents

Personalized Medicine What is it? Developing drugs on the basis of individual genetic differences How does it work? Tailoring therapies to genetically similar subpopulations results in improved efficacy and less toxicity What is it based upon? Pharmacogenomics = Pharmacology + Genomics

What is it?

Developing drugs on the basis of individual genetic differences

How does it work?

Tailoring therapies to genetically similar subpopulations results in improved efficacy and less toxicity

What is it based upon?

Pharmacogenomics = Pharmacology + Genomics

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

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

SNPs Occur when a single nucleotide (A,T,C,or G) in the genome sequence is altered, e.g., A A GGCTAA to A T GGCTAA Comprise 90% of all human genetic variation Exist every 100 to 300 bases along the 3-billion-base human genome Found in both coding (i.e., gene) and noncoding regions of the genome. Usually have no effect on cell function, but some could predispose people to disease or influence their response to a drug

Occur when a single nucleotide (A,T,C,or G) in the genome sequence is altered, e.g., A A GGCTAA to A T GGCTAA

Comprise 90% of all human genetic variation

Exist every 100 to 300 bases along the 3-billion-base human genome

Found in both coding (i.e., gene) and noncoding regions of the genome.

Usually have no effect on cell function, but some could predispose people to disease or influence their response to a drug

Ethical Hotspots Economic Pandora Research Social Clinical

Economic Research Clinical Social Ethical Issues: Research

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 Demonstrating Utility: Just because a mutation is associated with a specific disease does not mean its gene would make an effective drug target.

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

Economic Research Clinical Social Ethical Issues: Clinical

Clinical Issues Putting Testing into Practice : 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?

Putting Testing into Practice :

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 Family History Pharmacogenomics Profile Manage Protect Create Confidentiality Privacy Patient Record Current Health Status

Economic Research Clinical Social Ethical Issues: Social

Social Issues • Impact of individual allelic variations on identity (i.e., diversity and ethnicity) Effect(s) on health care inequalities Will more information make our world a better place?

• Impact of individual allelic variations on identity (i.e., diversity and ethnicity)

Effect(s) on health care inequalities

Social Issues Challenges: • Preventing discrimination: Insurance Jobs Educational opportunities • Legal implications: Regulation Enforcement Prosecution Restitution

Social Issues 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 (e.g., smoking, junk food, not exercising, etc.) if I don’t have a particular disease susceptibility? Health Horoscope

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 (e.g., smoking, junk

food, not exercising, etc.) if I don’t have a particular disease susceptibility?

Economic Clinical Research Social Ethical Issues: Economic

Economic Issues Pharmaceutical Business Decisions: Deciding which pharmacogenomics profile(s) to develop therapies for (e.g., fate of “orphan polymorphisms”) Hoarding SNP mutations to gain a market advantage What are the public health consequences of these decisions?

Pharmaceutical Business Decisions:

Deciding which pharmacogenomics profile(s) to develop therapies for (e.g., fate of “orphan polymorphisms”)

Hoarding SNP mutations to gain a market advantage

Economic Issues Unknown Costs: Pharmacogenomics testing Unnecessary preventative interventions (e.g., surgery, prophylaxis, etc.) Impact of healthier, aging population on economy

Unknown Costs:

Pharmacogenomics testing

Unnecessary preventative interventions (e.g., surgery, prophylaxis, etc.)

Impact of healthier, aging population on economy

Individuals and Society New opportunities for discrimination Eroding privacy and confidentiality Increasing cost of heath care Creating feelings of fatalism and helplessness Rising disparities between insured and under- and uninsured Accelerated drug development Simplified clinical trials Reduced adverse events Powerful, customized drugs Effective disease prevent strategies Balance Help Harm

New opportunities for

discrimination

Eroding privacy and

confidentiality

Increasing cost of heath

care

Creating feelings of

fatalism and helplessness

Rising disparities between

insured and under- and

uninsured

Accelerated drug development

Simplified clinical trials

Reduced adverse events

Powerful, customized drugs

Effective disease prevent strategies