Beyond and Decisions: From Problem Formulation to Dose- Response

Purpose To continue the discussion set forth by the National Academy of Science’s Science and Decisions: Advancement of Risk Assessment (2008), toward a unified approach to dose response assessment. Workshop 1: Sharing information and case study proposals Workshop 2: Expert panel leads evaluation of full case studies and makes recommendations Workshop 3: Panel builds consensus on dose-response assessment methods, develops peer reviewed publications and/or a guidance document that will serve as a resource for regulators and scientists on key considerations for applying selected dose-response techniques for various problem formulations.

Multistakeholder 25 co-sponsoring organizations – 6 government agencies – 6 scientific societies/subgroups – 5 non-profit organizations – 2 consulting groups – 6 industry groups More groups welcome And you – thank you to all participants, in person and via webcast

General Workshop Objectives Build off of the NAS (2008) report on improving the risk assessment process to develop practical guidance for use by risk managers at a variety of levels (e.g., states, regional managers, people in a variety of agencies, and in the private sector) for risk assessment techniques applicable to specific problem formulations. Implement a multi-stakeholder approach to share information, ideas and techniques in support of developing practical problem-driven risk assessment guidance.

Specific Workshop Objectives Identify useful dose-response techniques for specified problem formulations, including characterization of assumptions, strengths and limitations, and how the techniques address key considerations in the dose-response. These techniques should appropriately reflect the relevant biology (including the biology of thresholds), and mode of action information, at a level of detail appropriate for the problem formulation.

Specific Workshop Objectives (continued) Provide methods to explicitly address human variability in cancer assessment, and enhance the consideration of human variability in noncancer assessment, including explicit consideration of underlying disease processes. Identify methods for calculating the probability of response for noncancer endpoints. Develop peer reviewed publications and/or a guidance document that will serve as a resource for regulators and scientists to refer to for guidance on key considerations for applying selected dose-response techniques for various problem formulations.

Agenda for This Workshop Day 1 and morning of Day 2– Keynotes, ongoing activities, perspectives – What methods are available to aid in purpose- driven assessments? – Engage in discussion on issues – Stimulate thinking for case study proposals

Agenda for This Workshop Day 2 afternoon and Day 3 morning – case study proposals – Plenary – questions and brainstorming – Breakouts – further discussion Signups needed from in-person participants – Report back from breakouts Day 3 afternoon – Open discussion on improvements to the risk assessment process

Purpose of Case Studies and Next Steps Case studies to provide practical examples of purpose-driven risk assessment methods Test approaches and provide methods to address questions and issues raised in the NAS report Meeting report will focus on moving the case studies forward – initial evaluation on whether to bring forward, recommendations for implementing, issues to consider and address