Pharmacogenomics and Pharmacoepidemiology
Slide 1 of 12: Cancer Pharmacogenomics: Setting a Research Agenda to Accelerate Translation
Andrew N. Freedman, Ph.D.
Clinical and Translational Epidemiology Branch
Division of Cancer Control and Population Sciences
National Cancer Institute
Bethesda, MD
July 21, 2009
Slide 2 of 12: Outline
- Background
- Personalized Cancer Medicine
- Pharmacoepidemiology
- Pharmacogenomics (PGx)
- Conceptual Model
- Workshop Agenda
Slide 3 of 12: Currently Approved Oncology Drugs
[Image] shows a chart depicting the increase in the number of currently approved oncology drugs from 1950 to the 2000s. During this timeframe, there were typically five or fewer approved oncology drugs each year; however, the numbers have risen to over 20 approved oncology drugs per year based on data from the FDA’s Center for Drug Evaluation and Research.
Source: JNCI. 2007; 99 (5): 344. Reprinted by permission of Oxford University Press.
Slide 4 of 12:
[Image] shows covers of The Future of Drug Safety published by the Institute of Medicine, two Department of Health and Human Services Reports (Realizing the Potential of Pharmacogenomics: Opportunities and Challenges; U.S. System of Oversight of Genetic Testing: Response to the Charge of the Secretary of Health and Human Services), a report by the President’s Council of Advisors on Science and Technology (Priorities for Personalized Medicine).
Slide 5 of 12: Personalized Cancer Medicine
- Tailoring medical cancer prevention and treatment therapies to the individual characteristics of each patient improving their quality of life and health outcome.
- "The right medicine to the right person at the right dosage at the right time."
- Cancer Pharmacoepidemiology
- Cancer Pharmacogenomics
Slide 6 of 12: Cancer Pharmacoepidemiology
- The study of the benefits and risks of drug therapy outcomes among groups and subgroups of cancer patients
- Evaluation of an individual’s age, environment, diet, lifestyle factors, health status and response to drugs
Slide 7 of 12: Cancer Pharmacogenomics (PGx)
- Study of how variation in an individual’s germline and/or tumor genome are related to their metabolism and physiological response to drugs used in cancer prevention and treatment
- DNA sequence
- Copy number
- Methylation patterns
- Molecular biomarkers
- Gene expression
Slide 8 of 12: Pharmacoepidemiology and PGx
- Identify clinical, epidemiologic and genomic/molecular factors are associated with response and/or toxicity to cancer prevention and treatment therapies
- Benefits
- Select Optimal Therapy
- Reduce adverse drug reactions
- Reduce time, cost and failure rate of clinical trials
- Rescue drugs that are failing in clinical trials
- Rescue drugs withdrawn from the market
- Shift emphasis in clinical practice from reaction to prevention
Slide 9 of 12: Accelerating Translation
- Advances in molecular medicine and biotechnology
- Increasing use of electronic health records (EHRs)
- Increased availability of existing research infrastructures
Connect basic, clinical and population science discoveries to research in health care delivery systems: Move research to "where the patients are".
Slide 10 of 12: Cancer Pharmacogenomics: Setting a Research Agenda to Accelerate Translation
- Workshop Goal: To evaluate and Revise Trans-NCI PPWG recommendations
- Workshop Participants:
- NCI: DCTD, DCB, DCEG, DCCPS, DCP, CCR, CRCHD
- NIH: NIGMS, NHLBI, NHGRI, NCCR
- HHS: OD, FDA, CDC, AHRQ, CMS
- Research Networks: Cooperative Groups, PGRN, HMO-CRN, SEER, Cohort and Case-Control Consortia
- DOD and VA
- Industry
- Pharmacy Benefit Providers
- Academic Medical Institutions
- Comprehensive Cancer Centers
- Health Maintenance Organizations
- Advocates
Slide 11 of 12: Workshop Agenda
- Speaker 1: Richard M. Weinshilboum, M.D.
Topic 1: Cancer Pharmacogenomics: Development, Science, Translation - Speaker 2: Mark J. Ratain, M.D.
Topic 2: Challenges in the Design and Conduct of Clinical PGx Studies - Speaker 3: Howard McLeod, Pharm.D.
Topic 3: Interventional Pharmacogenetics: Moving the Science into Practice - Speaker 4: Robert S. Epstein, M.D., M.S.
Topic 4: Applications of Cancer PGx in a Naturalistic Setting - Speaker 5: Geoffrey S. Ginsburg, M.D., Ph.D.
Topic 5: Genome Guided Clinical Trials to Evaluate the Clinical Utility of Cancer PGx - Panel Discussion
- Moderator: Richard Schilsky, M.D.
- Panelists: Geoffrey Liu, M.D., David Flockhart M.D., Ph.D., and Cornelia M. Ulrich, Ph.D.
- LUNCH
- Breakout Working Groups
Slide 12 of 12: Breakout Working Groups
- Working Group A Moderators
- Rochelle M. Long, Ph.D., National Institute of General Medical Sciences (NIGMS)
- Robert L. Davis, M.D., Center for Health Research, Kaiser Permanente of Georgia
- Working Group B Moderators
- Lawrence J.Lesko, Ph.D., Center for Drug Evaluation and Research, FDA
- Sheila R. Weiss Smith, Ph.D., Center for Drug Safety, University of Maryland
- Working Group C Moderators
- Lori M. Minasian, M.D., Division of Cancer Prevention (DCP), NCI
- Muin J. Khoury, M.D., Ph.D., Office of Public Health Genomics, CDC