Cancer Pharmacogenomics: Setting a Research Agenda to Accelerate Translation

Slide 1 of 17: Workshop Overview & Objectives

Leah B. Sansbury, Ph.D., M.S.P.H
Clinical and Translational Epidemiology Branch
Division of Cancer Control and Population Sciences
National Cancer Institute
Bethesda, MD
July 21, 2009

Slide 2 of 17: Outline

  • Trans-NCI Pharmacoepidemiology and Pharmacogenomics Working Group (PPWG)
  • Formation, Structure and Progress
  • Goals of the PPWG and Subgroups
  • Development of the PPWG Recommendations
  • Goals and Objectives of the Workshop

Slide 3 of 17: Trans-NCI PPWG Progress

Image shows the PPWG timeline. Several people at NCI who had been working in the area of pharmcoepidmeiology, genetics, and health services research met to discuss the need for synthesizing the current state of the research at NCI and how to best plan Institute-wide initiatives to move the field forward.

After meeting with a number of researchers throughout the NCI, NIH, and other government agencies who worked in the areas of pharmacoepidemiology and pharmacogenomics, we decided that we needed to organize a trans-NCI working group focused on pharmacoepidemiology and pharmacogenomics.

In September 2007, a group presented a proposal to the director of NCI. In October 2007 the Trans-NCI Pharmacoepidemiology and Pharmacogenomics Working Group (PPWG) was chartered. Each division director nominated 1-2 individuals from their division to serve on the PPWG and the chairs of the 3 subgroups were identified in November 2007. In December 2007, the subgroup chairs met to discuss PPWG goals as well as goals for the three subgroups – basic sciences, clinical trials, and population sciences.

Slide 4 of 17: Translation of Cancer Pharmacoepidemiology and Pharmacogenomics

Image indicating the integration of basic biomedical research, clinical research, and population research and the translation of research findings from each area in the disciplines of cancer pharmacoepidemiology and pharmacogenomics. The image also gives examples of funding agencies for each focus area and examples of current funding.

Slide 5 of 17: Trans-NCI Pharmacogenomics & Pharmacoepidemiology Working Group (PPWG)


  • Develop recommendations to support the development of a comprehensive and interdisciplinary pharmacoepidemiology (PE) and pharmacogenomics (PGX) cancer research program in order to accelerate the translation of discoveries in basic, clinical and population research to enhance personalized therapy
  • Provide support for the discovery of clinical, epidemiologic and genomic factors that are associated with:
    • adverse effects and enhanced response of cancer prevention and treatment therapies
    • commonly-prescribed pharmaceuticals and risk of cancer

Slide 6 of 17: Basic Science Subgroup Goals

Chair: Doug Figg, Ph.D.

  • Facilitate the development and application of pharmacogenomic technologies for drug discovery and diagnostic development
  • Identify novel genetic variants and expression profiles involved in drug metabolism
  • Relate genomic associations observed in clinical and observational studies to protein function

Slide 7 of 17: Clinical Trials Subgroup Goals

Chair: Lori Minasian, M.D.

  • Identify opportunities, resources, and methodologies needed to incorporate genomic biomarkers and genomic tests in the design and analysis of clinical trials
  • Identify NCI-sponsored Phase II/III trials that have prospectively collected biospecimens
  • Explore the opportunity to develop electronic pooling of adverse event data
  • Establish funding mechanisms and guidelines for standardized sample collection, storage, and processing of biospecimens

Slide 8 of 17: Population Sciences Subgroup Goals

Co-Chairs: Leah Sansbury, Ph.D., & Nathaniel Rothman, M.D., M.P.H.

  • Identify opportunities and data infrastructures to investigate clinical and epidemiologic factors related to the response and toxicity of pharmaceuticals used in the treatment and prevention of cancer
  • Provide a platform to conduct targeted observational studies to identify genomic variants related adverse events and enhanced response of cancer prevention and treatment therapies
  • Provide evidence for clinical utility of these novel genomic markers

Slide 9 of 17: Additional Goals of the PPWG

  • Enhance communication, coordination, and collaboration of PE and PGX research across NCI
  • Engage other NIH ICs and federal agencies in PE and PGX research
  • Identify infrastructures and resources that are needed to advance PE and PGX cancer research
  • Leverage existing research efforts by other HHS agencies
  • Partner with federal healthcare delivery agencies to conduct and support PE and PGX research
  • Plan a workshop to review recommendations
  • Include other government agencies, extramural community, and industry

Slide 10 of 17: Trans-NCI PPWG Progress

Image shows a timeline depicting PPWG progress. After the subgroup chairs met in December 2007 to discuss goals for the PPWG and its subgroups, a kick-off meeting was held in January 2008 with the entire PPWG.

From February through June 2008, the PPWG subgroups met individually to work on recommendations related to their areas of research. In July 2008, the subgroup chairs met to present their recommendations and draft a set of recommendations from the group. These were presented to the NCI Division Directors in August 2008.

After the subgroup chairs received feedback from the Division Directors, the PPWG held a final meeting with all PPWG members to discuss the draft recommendations. In September 2008, the Subgroup Chairs briefed Dr. Niederhuber on the proposed recommendations. The Subgroup Chairs also presented the draft recommendations to the NCI Executive Committee. Finally, in January 2009, the PPWG report was prepared.

As previously mentioned, the PPWG wanted to receive input from researchers in the field of pharmacoepidemiology and pharmacogenomics (PGx) outside of NCI and thus the PPWG planned a Trans-NCI PGx workshop to bring experts in the field together to evaluate its recommendations. This is the reason why we brought you all together today. Our plan, after we receive feedback today, is to publish our recommendations.

Slide 11 of 17: Workshop Objectives

  • To evaluate the recommendations of the Trans-NCI PPWG in order to develop a comprehensive and integrated scientific agenda to accelerate the translation of this research from discovery to application
  • To ensure the PPWG's recommendations help NCI focus on the most promising research opportunities that will move the field of pharmacogenomics forward in the areas of basic science, clinical trials and the population sciences

Slide 12 of 17: Responses to NIH Pharmacogeomics Working Group Request for Information

Image shows a graph of responses to the NIH Pharmacogenomics Working Group Request for Information, including the average number of comments on various topics, the weighted priority, and the actual number of responses. Three main themes included adequacy of sample sizes, appropriate phenotypes for drug response, and genotype-guided studies.

Slide 13 of 17: Current Pharmacogenomics Support at NCI

Image shows a pie chart indicating the percentage of NCI’s 2007 research funding dollars from NCI’s 6 Divisions relevant to pharmacogenomics research. The percentage was 1.4%, which is is approximately $38.8 million. The total NCI FY07 budget was $4.8 billion.

Slide 14 of 17: Portfolio Analysis

Pharmacogemomic Research Portfolio Summary:

  • Number of Relevant Awards in 2007 = 98
  • Percentage of Total NCI Awards* = 1.2%
  • 2007 Funding ($ in millions) = $38.8
  • Percent of Total NCI Budget* = 0.8%
  • Funding to Six Divisions/Centers in 2007 ($ in Millions) = $2,815
  • Percentage of FY 2007 Pharmacogenomic Funding to Research Funding across Six Divisions/Centers = 1.4%

*Total NCI portfolio in FY 2007 was 8,302. Total NCI budget in FY 2007 was $4.8B.

Slide 15 of 17: Ongoing and Developing Activities in Pharmacoepidemiology and Pharmacogenomics: Basic Science

Pharmacogenetics Research Network (PGRN)External Web Site Policy

  • Effect of genetic variants on the pharmacokinetics and pharmacodynamics of anticancer agents
  • Contribution of genetic variants to the efficacy and toxicities of endocrine treatments for breast cancer
  • Pharmacogenetics of Phase II Drug Metabolizing Enzymes

Slide 16 of 17: Ongoing and Developing Activities in Pharmacoepidemiology and Pharmacogenomics: Clinical Science

  • NCI-sponsored pharmacogenomics correlative studies
  • RIKEN collaboration
  • The Breast Cancer Intergroup (TBCI)
    • Pharmacogenomics meeting, March 2008
    • Support correlative studies
  • MARVEL lung cancer trial

Slide 17 of 17: Ongoing and Developing Activities in Pharmacoepidemiology and Pharmacogenomics: Population Science

  • HMO-CRN cardio toxicity and breast cancer treatment demonstration project
  • PGRN population science supplements
  • NCI-VA Study on Erythropoietin (EPO)
  • SEER-Medicare study of biologic therapies for cancer

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