T14 - Recent Developments in Risk Assessment: Methods and ApplicationsSierra 1:30 - 3:00 pm
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| Chair(s): Susan Poulter
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T14.1 Incorporating Genomics into Agency Risk Assessments and Regulations. G.E. Marchant; Arizona State University gary.marchant@asu.edu
Abstract: Genomic information has the potential to greatly affect health risk assessment and transform health and environmental regulatory decision-making. Over the past year, federal agencies have begun taking concrete steps to lay the framework for the use of genomic data in risk assessment and regulation. The Environmental Protection Agency has recently issued an Interim Genomics Policy and a draft Genomics White Paper. Similarly, the Food and Drug Administration has released for public comment a Draft Guidance for Industry on Pharmacogenomic Data Submissions. This presentation will describe and comment on recent federal agency initiatives to incorporate genomic data in risk assessment and regulatory decisions, focusing on the potential benefits of genomic data in such applications and the challenging policy, legal and ethical issues that will be raised.
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T14.2 The Impact of Toxicogenomics on Public Health Policy, Risk Assessment and Regulation . B.A. Merrick, J.K. Selkirk; NIEHS, National Center for Toxicogenomics merrick@niehs.nih.gov
Abstract: The new science of toxicogenomics promises to revolutionize the practice of public health and risk assessment as applied to environmental health protection. Understanding human genetic variation and genomic reactions to specific environmental exposures will have a significant impact to assess human response to environmental exposures. Toxicogenomics will eventually help reduce costs and time lines for animal and human studies for efficacy and toxicity. Debates on risk assessment often involve levels of comfort with the default assumptions with the potential for standards to be set at needlessly low levels and little added public health benefit. Decisions based on detailed toxicity, mechanistic, and exposure data can reduce uncertainty. Given the number of drugs, chemicals and environmental agents, the diversity of exposed species, the time and dose factors that are critical to the induction of beneficial and adverse effects, it is only through the development of a profound toxocogenomics knowledgebase on global molecular expression that toxicology and environmental health can rapidly advance. Through the creation of the National Center for Toxicogenomics, its university-based Toxicogenomics Research Consortium, and supportive Resource Contracts, the NIEHS has embarked on the development, application and standardization of the science to the build a knowledgebase on Chemical Effects in Biological Systems (CEBS). CEBS will contain the documentation, for multiple classes of agents, about what constitutes a homeostatic or compensatory alteration in global gene or protein expression, as opposed to a pharmacological response to a drug, or a toxic response to an environmental chemical. As with any nascent science, initial costs must be met and experience must be gained before the promise can be fulfilled. Thus, it must be understood that progress in realizing the full promise that toxicogenomics and computational toxicology can bring to environmental health protection and risk assessment will not occur in great leaps but rather through sustained, incremental steps.
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T14.3 TRANSLATION OF PHARMACOGENOMICS INTO PATIENT CARE: RISK ASSESSMENT IN SPECIAL POPULATIONS.. L. Lesko; FDA Center for Drug Evaluation and Research leskol@cder.fda.gov
Abstract: A societal challenge for health care providers is to assure a high degree of certainty with regard to achieving the desirable effects of a drug, while avoiding the undesirable effects, in patients receiving the usual approved doses. Pharmacogenomics has the potential to improve the preferred degree of certainty by accounting for variability in the exposure-response relationships for efficacy and safety between patients. In assessing the current state of pharmacogenomics, the translation of the science into patient benefit has been disappointing. Despite the body of literature that has related pharmacogenomic variants to drug response (e.g., thiopurine methyltransferase alleles and 6-mercaptopurine toxicity), widespread adoption of pharmacogenomic tests to manage risks of toxicity and guide dosing has not occurred. The FDA has stated that one of its priorities under its critical path initiative is to advance the application of pharmacogenomics. (http://www.fda.gov/oc/initiatives/critical path/whitepaper.html) Recent experience with attempts to encourage integration of pharmacogenomics into new drug development and to update certain approved product labels to include pharmacogenomic data have highlighted the challenges in front of us. This presentation will focus on the issues that arise during a discussion or debate of using pharmacogenomics in drug development (e.g., assessing the role of pharmacogenomics on the shape of the exposure-response curves for efficacy and safety) or including pharmacogenomic data in package inserts (e.g., strength of the evidence of clinical utility) in order to assess and manage the risks of toxicity. Some recent successes for moving pharmacogenomics to the clinic will be discussed.
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T14.4 Advances in Risk Assessment: New Challenges, New Opportunities. P.W. Preuss; National Center for Environmental Assessment, U.S. Environmental Protection Agency, Washington,
Abstract: The EPA has a mandate to evaluate and protect human and natural systems from the adverse impacts of environmental pollution. Risk assessment procedures are used to understand the impacts of pollution, as well as to characterize the benefits of control strategies and to characterize the strengths and limitations of our knowledge. Advances in scientific understanding present challenges and opportunities to risk assessors in the interpretation and application of knowledge gained. In this presentation the EPA’s actions to evaluate new scientific findings, to review Agency risk assessment practices, and to advance human health risk assessments through new assessment procedures, new science policy guidance, new engagement of external peer reviewers, and new relationships between the research, assessment and user communities, will be discussed.
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