Examples in Stakeholder Collaboration for Risk Assessment Science

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Examples in Stakeholder Collaboration for Risk
Assessment Science

• Andrew Maier
• Jacqueline Patterson
• Michael Dourson

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Presentation Overview

• A few words on the importance of collaboration
• Some examples of collaborative processes
• Take home message
• We are all committed to protecting public
  health, although the issues are frequently
  complex they can often be solved through
  collaborative approaches (well get farther
  faster).

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Toxicology Excellence for Risk Assessment

• About TERA
• A non-profit, 501(c)(3) corporation
• Mission to protect public health
• Founded in 1995 with a current technical staff of
  12 and several visiting scientists and
  associates.
• Completes roughly 50 technical projects per year
  for government and industry sponsors (strives for
  5050 balance) in areas including developing
  chemical assessments, risk methods development,
  and peer review and consultation provides ITER
  database
• Focus on solving risk science issues through 1)
  technology leadership, 2) building bridges among
  stakeholder groups
• http//www.tera.org

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Key Benefits of Collaboration

• Promotes science-based decision making to protect
  human health by ensuring all key data and ideas
  are fully considered
• Enhances harmonization and consistency in risk
  assessments thru an open, transparent,
  multi-stakeholder approach that ultimately foster
  harmonization and information sharing
• Makes use of groups of experts that are normally
  not available within a single organization
• Shares costs and human resources among multiple
  stakeholders to increase output for the broader
  risk community
• This can all be achieved while allowing groups to
  control their own process and can receive broad
  acceptance with thoughtful management of biases

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Benefits of Collaboration

• Many international initiatives reflect desire of
  risk science community for increasing
  partnerships
• SRA Europe June 2007 Building Bridges Issues
  for Future Risk Research
• International Programme for Chemical Safety
  (IPCS) Harmonization Project

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Harmonization

• Harmonization is not standardization
• Understanding the methods and practices used by
  various organizations
• Developing confidence in and acceptance of
  assessments using different approaches
• Willingness to work toward a convergence of
  methodologies as long-term goal

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Does similar momentum for collaboration exist in
U.S.? Yes - we think so.
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A Few Examples of Collaboration

• Peer involvement processes - Voluntary Childrens
  Chemical Evaluation Program
• Genotoxicity MOA Cooperative Research and
  Development Agreement (CRADA)
• Alliance for Risk Assessment (ARA)

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Peer Involvement
Peers Experts of equal standing as the authors
Peer Involvement Gathering advice and review on
risk assessment products from peers
Peer Review a formal, external, and independent
review of an intended final work product
Peer Input soliciting information, data, or
opinion, generally at an early stage of a work
products development
Peer Consultation a formal or informal process
to gather expert peer opinion and advice on a
work product
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Development Stage Type of Peer Involvement
Problem Formulation, Issue Identification, and Data Gathering Peer Input Data requests Workshops, Meetings , informal or formal Informal discussions Expert Elicitation to fill data gaps or address uncertainties
Draft Work Product Peer Consultation Requests for written comments or review Panel meetings or conference calls On single issues or entire work product
Final Draft Work Product Peer Review Written or letter review Panel meetings or conference calls On near final work product
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VCCEP

• A joint effort of multiple stakeholders
• Companies that manufacture, import, or use
  chemicals covered by TSCA
• EPA OPPT
• Childrens health groups
• Chemical testing interest groups
• Animal welfare groups
• Purpose - to enable the public to better
  understand the potential health risks to children
  associated with certain chemical exposure
• Industry prepares assessments of hazard, exposure
  and risk to children and recommends data gaps and
  data needs.
• Assessments reviewed by diverse and balanced
  panels under TERA peer consultation program.
  Core and ad hoc panel members used.
• EPA uses PC report as input as it decides whether
  further testing is needed.

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TERAs Role in VCCEP

• Under a Cooperative Agreement from EPA, TERA is
  designing, developing and managing a Peer
  Consultation process to serve as a public
  scientific forum. One of the major activities
  undertaken by TERA under this agreement is the
  VCCEP.
• TERAs primary role in managing the VCCEP Peer
  Consultation is to ensure that it is a rigorous,
  science-based process for reviewing chemical
  assessments that stakeholders recognize as
  impartial and of significant technical merit and
  value.
• TERA selects panelists, conducts all aspects of
  the meetings, and prepares the reports.

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Using Peer Involvement to Advance Resolution of
Pesticide Issues

• Industry develops document or work product
• Vetted by Independent Peer Consultation Panel in
  an open and transparent fashion
• Shared with EPA and others for their potential
  use as input to support decision-making
• A supplement to EPA SAP for appropriate issues
• Captan cancer reclassification is an example of
  such an application of the process

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Captan Tumor Mode of Action

• A Success Story in Stakeholder Involvement
• EPAs cancer assessment for Captan was based on
  EPAs 1986 Cancer Guidelines.
• EPA OPP indicated they were not planning a
  re-evaluation, but would consider an
  independently reviewed reassessment.
• The Captan Task Force sponsored an updated
  analysis, which supported a non-linear mode of
  action.
• TERA convened an independent peer review panel.
  The panel provided several recommendations, but
  agreed with the nonlinear mode of action.
• EPA OPP accepted the conclusions of the
  independent peer review.
• See www.tera.org/peer/CAPTAN/CAPTANWelcome.htm

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A NEW STRATEGY TO IDENTIFY CHEMICALS THAT ARE
MUTAGENS AND CARCINOGENS BUT NOT NECESSARILY
MUTAGENIC CARCINOGENS
NCTR Martha Moore, Robert Heflich TERA Lynne
Haber, Mike Dourson ENVIRON Annette Shipp,
Robinan Gentry Bruce Allen Consulting Bruce
Allen University of Arkansas for Medical
Sciences Ralph Kodell
Disclaimer Not Official FDA Policy
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MOA CRADA

• Stakeholder identifies chemical for which
  reassessment of Cancer MOA is needed
• NCTR conducts in vivo mutagenicity/
  tumorigenicity assay
• NCTR, TERA, Environ evaluate mutation frequency
  and tumor data to test concordance with Hill
  criteria (dose-response and temporal response)
• Analysis provided to EPA to consider in weight of
  evidence for cancer reassessments

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Design for in vivo Mutation Studies Addressing
Cancer MOA

• Use transgenic model that will detect point
  mutations (base pair subs, frameshifts, very
  small deletions/insertions)
• Big Blue transgenic model
• Chronic treatment (up to 12 months) modeled on
  the tumor bioassay
• Same species/strain as cancer study
• Same exposure route as cancer study
• Detection of mutation in the target tissue(s)
• Multiple doses (6 or 7) based on tumor
  data--Enough doses to adequately characterize the
  dose response
• Evaluate mutation, toxicity, cell proliferation
  at 28 days, 3, 6, 9, 12 months (Time-to-mutation)

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Riddelliine Dose Response Concordance
Fitted dose-response curves for MF and cancer
incidence on a probability scale. Cancer
dose-response ( ) is based on fitting a
multistage model. Two probability dose-responses
for MF are shown, resulting from different
assumptions regarding the background rate of
response (0.058 or 0.01).
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DCA Dose Response Concordance
Fitted dose-response curves for MF and cancer
incidence on a probability scale. Cancer
dose-response ( ) is based on fitting a
multistage model. Two probability dose-responses
for MF are shown, resulting from different
assumptions regarding the background rate of
response (0.26, -- -- -- or 0.01, -------).
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Alliance for Risk Assessment (ARA)

• A process to facilitate communication and
  collaboration toward development of useful and
  timely risk science products.

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Alliance for Risk Assessment (ARA)
Alliance Menu Options
Stakeholder Process
States, Fed. Agencies, Public Interests,
Industry
Steering Committee
Risk Document Development
Initiation of Risk Issue
Training and Certification
Non-profit Collaborators
Hazard Assessment Notification System (HANS)
Risk Communication
Document Draft
Risk Research And Tools
Peer Reviews
Peer Consult
Peer Review
Release to Public
ITER
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ARA Work Flow
Steering Committee
Federal Agencies, Industry
Funded Projects
Hazard Assessment Notification System (HANS)
TERA and Non-Profit Collaborators
States, Tribes, Env. NGOs
Unfunded Project Requests
ITER
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ARA Funds Flow
ARA Process
Federal Agencies
Federal Funds
Federal Funds
Unfunded Projects
100 Risk Issues per Year by Year 5
Contracts
Funded Projects
Industry
Contracts
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The ARA Sand Box

• The ARA seeks collaboration building and there is
  a role for all players
• Players federal government, local government,
  tribes, industry, for-profit consultants, NGOs.
• Roles
• users - use of work products, use of information
  exchange, work product vetting,
• experts assisting other (e.g., peer review panel
  member)
• developing work products
• Steering Committee membership

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ARA Steering Committee

• Provides advice to ARA Partners on mission-
  relatedness, project prioritization, Conflict of
  Interest,
• Scientists
• 2 States
• 1 Tribe
• 1 Env. Group
• 2 Federal
• 1 Industry
• 1 Academic
• 2 ARA Partners

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Why Would Diverse Groups Provide Funding?

• The Alliance for Risk Assessment (ARA) mission
• Aligns with many public health goals.
• Provides value as a timely resource for technical
  products with enhanced credibility.
• Allows Stakeholder input e.g., via involvement
  in Science Steering Committee, as participants in
  technical panels.
• Gives an opportunity for harmonizing risk values
  and methods which eases burden for stakeholders
  that must meet requirements in multiple
  constituencies.
• Over the years nonprofit corporations have
  demonstrated the concept can work e.g., peer
  consultation with Voluntary Childrens Chemical
  Evaluation Program (VCCEP) of EPA.
• NLM TERA have success in building ITER
  200,000 hits per year demonstrates likely value
  of ARA
• Aligns with stated needs of stakeholders e.g.,
  Environmental Council of States (ECOS) call for
  harmonized process.

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NLMs Toxnet
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Does Stakeholder Interest Exist?

• In exploring the needs for this ARA, TERA has
  provided briefing and/or received input from many
  potential stakeholders (over 100 individuals)
  Including
• 30 States
• 2 Tribes
• 4 Environmental NGOs
• 30 Industry groups
• 6 U.S. Federal Agencies
• 4 Countries
• Feed back has been positive. Suggestions have led
  to refinements in the proposed ARA. Nearly all
  responding contacts have encouraged moving
  forward.
• Diverse groups are beginning to provide funding
  or suggest projects

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Does This Effort Duplicate Current Federal
Efforts?

• This effort does not duplicate ATSDR MRLs, EPA
  IRIS, FDA ADIs, Health Canada TDIs or RIVM TOCs.
• To the contrary, ARA shares resources to avoid
  duplication because
• It does not replace individual regulatory
  processes ARA users tap in as appropriate.
• Many risk values/issues will never be worked by
  federal groups.
• Current federal approaches have resource
  limitations thus, new chemicals addressed
  without duplicate effort.
• Update of older values can benefit federal groups
  as one technical input to internal deliberations.
• ARA goes beyond risk values/issues it is also a
  shared resource for training and data
  communication.

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ARA Supports Existing Risk Values

• Provides guidance for sources of toxicity
  information that may be used in performing human
  health risk assessments
• ITER can supplement existing toxicity data
• ARA can provide Tier III values

EPA OSWER Directive 9285.7-53
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www.allianceforrisk.org
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Summary

• We are all committed to protecting public health,
  although the issues are frequently complex they
  can often be solved through collaborative
  approaches (well get farther faster).

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Collaboration is Powerful
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Questions?