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Examples in Stakeholder
Collaboration for Risk Assessment
ScienceAndrew Maier
Jacqueline PattersonMichael Dourson
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Presentation Overview A few words on the importance of A few words on the importance of
collaborationcollaboration Some examples of collaborative processesSome examples of collaborative processes Take home message: Take home message:
We are all committed to protecting public We are all committed to protecting public health, although the issues are frequently health, although the issues are frequently complex they can often be solved through complex they can often be solved through collaborative approaches (we’ll get collaborative approaches (we’ll get farther faster).farther faster).
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Toxicology Excellence for Risk Toxicology Excellence for Risk AssessmentAssessment
About About TERA:TERA: A non-profit, 501(c)(3) corporation A non-profit, 501(c)(3) corporation Mission to protect public healthMission to protect public health Founded in 1995 with a current technical staff of Founded in 1995 with a current technical staff of
12 and several visiting scientists and associates. 12 and several visiting scientists and associates. Completes roughly 50 technical projects per year Completes roughly 50 technical projects per year
for government and industry sponsors (strives for for government and industry sponsors (strives for 50:50 balance) in areas including developing 50:50 balance) in areas including developing chemical assessments, risk methods development, chemical assessments, risk methods development, and peer review and consultation; provides and peer review and consultation; provides ITERITER databasedatabase
Focus on – solving risk science issues through 1) Focus on – solving risk science issues through 1) technology leadership, 2) building bridges among technology leadership, 2) building bridges among stakeholder groupsstakeholder groups
http://www.tera.orghttp://www.tera.org
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Key Benefits of Key Benefits of CollaborationCollaboration
Promotes science-based decision making to protect Promotes science-based decision making to protect human health by ensuring all key data and ideas are human health by ensuring all key data and ideas are fully consideredfully considered
Enhances harmonization and consistency in risk Enhances harmonization and consistency in risk assessments thru an open, transparent, multi-assessments thru an open, transparent, multi-stakeholder approach that ultimately foster stakeholder approach that ultimately foster harmonization and information sharingharmonization and information sharing
Makes use of groups of experts that are normally not Makes use of groups of experts that are normally not available within a single organizationavailable within a single organization
Shares costs and human resources among multiple Shares costs and human resources among multiple stakeholders to increase output for the broader risk stakeholders to increase output for the broader risk communitycommunity
This can all be achieved while allowing groups to This can all be achieved while allowing groups to control their own process and can receive broad control their own process and can receive broad acceptance with thoughtful management of biasesacceptance with thoughtful management of biases
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Benefits of CollaborationBenefits of Collaboration
Many international initiatives reflect Many international initiatives reflect desire of risk science community for desire of risk science community for increasing partnershipsincreasing partnerships SRA Europe – June 2007 : “Building SRA Europe – June 2007 : “Building
Bridges Issues for Future Risk Bridges Issues for Future Risk Research”Research”
International Programme for Chemical International Programme for Chemical Safety (IPCS) Harmonization ProjectSafety (IPCS) Harmonization Project
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Harmonization
Harmonization is not standardizationHarmonization is not standardization Understanding the methods and practices Understanding the methods and practices
used by various organizationsused by various organizations Developing confidence in and acceptance Developing confidence in and acceptance
of assessments using different approachesof assessments using different approaches Willingness to work toward a convergence Willingness to work toward a convergence
of methodologies as long-term goalof methodologies as long-term goal
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Does similar Does similar momentum for momentum for
collaboration exist collaboration exist in U.S.? in U.S.?
Yes - we think so.Yes - we think so.
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A Few Examples of Collaboration
Peer involvement processes - Voluntary Peer involvement processes - Voluntary Children’s Chemical Evaluation ProgramChildren’s Chemical Evaluation Program
Genotoxicity MOA Cooperative Research Genotoxicity MOA Cooperative Research and Development Agreement (CRADA)and Development Agreement (CRADA)
Alliance for Risk Assessment (Alliance for Risk Assessment (ARAARA))
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Peers:Experts of equal standing
as the authors
Peer Involvement:Gathering advice and
review on risk assessment products from peers
Peer Consultation: a formal or informalprocess to gather expert peer opinion and advice on a work product
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 product’s development
Peer Involvement
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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 ProductFinal Draft Work Product Peer ReviewWritten or letter review Panel meetings or conference calls On near final work product
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VCCEPVCCEP A joint effort of multiple stakeholders:A joint effort of multiple stakeholders:
Companies that manufacture, import, or use chemicals Companies that manufacture, import, or use chemicals covered by TSCAcovered by TSCA
EPA OPPTEPA OPPT Children’s health groupsChildren’s health groups Chemical testing interest groupsChemical testing interest groups Animal welfare groupsAnimal welfare groups
Purpose - to enable the public to better understand Purpose - to enable the public to better understand the potential health risks to children associated with the potential health risks to children associated with certain chemical exposure certain chemical exposure
Industry prepares assessments of hazard, exposure Industry prepares assessments of hazard, exposure and risk to children and recommends data gaps and and risk to children and recommends data gaps and data needs. data needs.
Assessments reviewed by diverse and balanced panels Assessments reviewed by diverse and balanced panels under under TERATERA peer consultation program. Core and peer consultation program. Core and ad ad hochoc panel members used. panel members used.
EPA uses PC report as input as it decides whether EPA uses PC report as input as it decides whether further testing is needed.further testing is needed.
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TERA’sTERA’s Role in VCCEP Role in VCCEP Under a Cooperative Agreement from EPA, Under a Cooperative Agreement from EPA,
TERATERA is designing, developing and managing a is designing, developing and managing a Peer Consultation process to serve as a public Peer Consultation process to serve as a public scientific forum. One of the major activities scientific forum. One of the major activities undertaken by undertaken by TERATERA under this agreement is under this agreement is the VCCEP. the VCCEP.
TERATERA’s primary role in managing the VCCEP ’s primary role in managing the VCCEP Peer Consultation is to ensure that it is a Peer Consultation is to ensure that it is a rigorous, science-based process for reviewing rigorous, science-based process for reviewing chemical assessments that stakeholders chemical assessments that stakeholders recognize as impartial and of significant recognize as impartial and of significant technical merit and value.technical merit and value.
TERATERA selects panelists, conducts all aspects of selects panelists, conducts all aspects of the meetings, and prepares the reportsthe meetings, and prepares the reports..
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Using Peer Involvement to Using Peer Involvement to Advance Resolution of Advance Resolution of
Pesticide IssuesPesticide Issues Industry develops document or work Industry develops document or work
product product Vetted by Independent Peer Consultation Vetted by Independent Peer Consultation
Panel in an open and transparent fashionPanel in an open and transparent fashion Shared with EPA and others for their Shared with EPA and others for their
potential use as input to support decision-potential use as input to support decision-makingmaking
A supplement to EPA SAP for appropriate A supplement to EPA SAP for appropriate issuesissues
Captan cancer reclassification is an Captan cancer reclassification is an example of such an application of the example of such an application of the processprocess
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Captan Tumor Mode of Captan Tumor Mode of ActionAction
A Success Story in Stakeholder InvolvementA Success Story in Stakeholder Involvement EPA’s cancer assessment for Captan was based on EPA’s cancer assessment for Captan was based on
EPA’s 1986 Cancer Guidelines.EPA’s 1986 Cancer Guidelines. EPA OPP indicated they were not planning a re-EPA OPP indicated they were not planning a re-
evaluation, but would consider an independently evaluation, but would consider an independently reviewed reassessment.reviewed reassessment.
The Captan Task Force sponsored an updated The Captan Task Force sponsored an updated analysis, which supported a non-linear mode of analysis, which supported a non-linear mode of action.action.
TERATERA convened an independent peer review panel. convened an independent peer review panel. The panel provided several recommendations, but The panel provided several recommendations, but agreed with the nonlinear mode of action.agreed with the nonlinear mode of action.
EPA OPP accepted the conclusions of the EPA OPP accepted the conclusions of the independent peer review.independent peer review.
See: See: www.tera.org/peer/CAPTAN/CAPTANWelcome.htmwww.tera.org/peer/CAPTAN/CAPTANWelcome.htm
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A NEW STRATEGY TO IDENTIFY CHEMICALS A NEW STRATEGY TO IDENTIFY CHEMICALS THAT ARE MUTAGENS AND CARCINOGENS BUT THAT ARE MUTAGENS AND CARCINOGENS BUT NOT NECESSARILY MUTAGENIC CARCINOGENSNOT NECESSARILY MUTAGENIC CARCINOGENS
NCTRMartha Moore, Robert Heflich
TERALynne Haber, Mike Dourson
ENVIRON Annette Shipp, Robinan GentryAnnette Shipp, Robinan Gentry
Bruce Allen ConsultingBruce Allen Consulting Bruce AllenBruce Allen
University of Arkansas for Medical SciencesUniversity of Arkansas for Medical Sciences Ralph Kodell
Disclaimer: Not Official FDA Policy
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MOA CRADAMOA CRADA
Stakeholder identifies chemical for which Stakeholder identifies chemical for which reassessment of Cancer MOA is neededreassessment of Cancer MOA is needed
NCTR conducts NCTR conducts in vivoin vivo mutagenicity/ mutagenicity/ tumorigenicity assaytumorigenicity assay
NCTR, NCTR, TERATERA, Environ evaluate mutation , Environ evaluate mutation frequency and tumor data to test frequency and tumor data to test concordance with Hill criteria (dose-concordance with Hill criteria (dose-response and temporal response)response and temporal response)
Analysis provided to EPA to consider in Analysis provided to EPA to consider in weight of evidence for cancer reassessmentsweight of evidence for cancer reassessments
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Design for Design for in vivoin vivo Mutation Mutation Studies Addressing Cancer MOAStudies Addressing Cancer MOA
Use transgenic model that will detect point Use transgenic model that will detect point mutations (base pair subs, frameshifts, very small mutations (base pair subs, frameshifts, very small deletions/insertions)deletions/insertions) Big Blue transgenic model Big Blue transgenic model
Chronic treatment (up to 12 months) modeled on Chronic treatment (up to 12 months) modeled on the tumor bioassaythe tumor bioassay
Same species/strain as cancer studySame species/strain as cancer study Same exposure route as cancer studySame exposure route as cancer study Detection of mutation in the target tissue(s)Detection of mutation in the target tissue(s) Multiple doses (6 or 7) based on tumor data--Multiple doses (6 or 7) based on tumor data--
Enough doses to adequately characterize the dose Enough doses to adequately characterize the dose responseresponse
Evaluate mutation, toxicity, cell proliferation at 28 Evaluate mutation, toxicity, cell proliferation at 28 days, 3, 6, 9, 12 months (Time-to-mutation)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 probabilityscale. Cancer dose-response ( ) is based on fitting a multistagemodel. Two probability dose-responses for MF are shown, resultingfrom 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 probabilityscale. Cancer dose-response ( ) is based on fitting a multistagemodel. Two probability dose-responses for MF are shown, resulting fromdifferent assumptions regarding the background rate of response(0.26, -- -- --; or 0.01, -------).
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Alliance for Risk Alliance for Risk Assessment Assessment
((ARAARA))A process toA process to facilitate communication and collaboration toward
development of useful and timely risk science products.
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Alliance for Risk Assessment Alliance for Risk Assessment
((ARAARA)) States,
Fed. Agencies, Public Interests,
Industry
Initiation ofRisk Issue
Document Draft
PeerReviews
Release toPublic
Hazard AssessmentNotification
System (HANS)
Risk DocumentDevelopment
Peer Consult
Risk ResearchAnd Tools
ITER
Training andCertification
Peer Review
Non-profitCollaborators
Alliance “Menu” OptionsStakeholder Process
RiskCommunication
SteeringCommittee
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ARA Work FlowARA Work Flow
Federal Agencies, Industry
Hazard AssessmentNotification
System (HANS)
ITER
SteeringCommittee
States, Tribes,
Env. NGOs
TERA andNon-Profit
Collaborators
Unfunded Project Requests
Funded Projects
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ARA Funds FlowARA Funds Flow
Federal Agencies ARAProcess
IndustryFundedProjects
Unfunded
Projects
Federal Funds
Federal Funds
Contracts
Contracts
100 Risk Issues per
Year by Year 5
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The The ARAARA Sand Box Sand Box The The ARAARA seeks collaboration building and seeks collaboration building and
there is a role for all players…there is a role for all players… Players: federal government, local Players: federal government, local
government, tribes, industry, for-profit government, tribes, industry, for-profit consultants, NGOs.consultants, NGOs.
Roles: Roles: users - use of work products, use of information users - use of work products, use of information
exchange, work product vetting, exchange, work product vetting, experts assisting other (e.g., peer review panel experts assisting other (e.g., peer review panel
member) member) developing work productsdeveloping work products Steering Committee membershipSteering Committee membership
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ARA Steering CommitteeARA Steering Committee Provides advice to ARA Partners on Provides advice to ARA Partners on
mission- relatedness, project mission- relatedness, project prioritization, Conflict of Interest, prioritization, Conflict of Interest,
Scientists:Scientists: 2 States2 States 1 Tribe1 Tribe 1 Env. Group1 Env. Group 2 Federal2 Federal 1 Industry1 Industry 1 Academic1 Academic 2 ARA Partners2 ARA Partners
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Why Would Diverse Why Would Diverse Groups Provide Funding?Groups Provide Funding?
The Alliance for Risk AssessmentThe Alliance for Risk Assessment (ARA) (ARA) mission…mission… Aligns with many public health goals.Aligns with many public health goals. Provides value as a timely resource for technical products Provides value as a timely resource for technical products
with enhanced credibility.with enhanced credibility. Allows Stakeholder input – e.g., via involvement in Science Allows Stakeholder input – e.g., via involvement in Science
Steering Committee, as participants in technical panels.Steering Committee, as participants in technical panels. Gives an opportunity for harmonizing risk values and Gives an opportunity for harmonizing risk values and
methods – which eases burden for stakeholders that must methods – which eases burden for stakeholders that must meet requirements in multiple constituencies.meet requirements in multiple constituencies.
Over the years nonprofit corporations have demonstrated the Over the years nonprofit corporations have demonstrated the concept can work [e.g., peer consultation with Voluntary concept can work [e.g., peer consultation with Voluntary Children’s Chemical Evaluation Program (VCCEP) of EPA].Children’s Chemical Evaluation Program (VCCEP) of EPA].
NLM & NLM & TERATERA have success in building have success in building ITERITER; ~200,000 hits ; ~200,000 hits per year demonstrates likely value of per year demonstrates likely value of ARAARA
Aligns with stated needs of stakeholders – e.g., Environmental Aligns with stated needs of stakeholders – e.g., Environmental Council of States (ECOS) call for harmonized process.Council of States (ECOS) call for harmonized process.
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ITER Daily Users
0
50
100
150
200
250
300
350
400
450
01/3 01/4 02/1 02/2 02/3 02/4 03/1 03/2 03/3 03/4 04/1 04/2 04/3 04/4 05/1 05/2 05/3 05/4 06/1 06/2
Year and Quarter
Nu
mb
er o
f U
sers
per
Day
National Library of Medicine
NSF Intl & IARC
IRIS, ATSDR & Health Canada
RIVM
Independent Values
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NLM’s ToxnetNLM’s Toxnet
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Does Stakeholder Does Stakeholder Interest Exist?Interest Exist?
In exploring the needs for this In exploring the needs for this ARAARA, , TERATERA has provided has provided briefing and/or received input from many potential briefing and/or received input from many potential stakeholders (over 100 individuals) Including:stakeholders (over 100 individuals) Including: 30 States30 States 2 Tribes2 Tribes 4 Environmental NGO’s4 Environmental NGO’s 30 Industry groups30 Industry groups 6 U.S. Federal Agencies6 U.S. Federal Agencies 4 Countries4 Countries
Feed back has been positive. Suggestions have led to Feed back has been positive. Suggestions have led to refinements in the proposed refinements in the proposed ARAARA. Nearly all . Nearly all responding contacts have encouraged moving forward.responding contacts have encouraged moving forward.
Diverse groups are beginning to provide funding or Diverse groups are beginning to provide funding or suggest projectssuggest projects
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Does This Effort Does This Effort Duplicate Current Duplicate Current Federal Efforts?Federal Efforts? This effort does not duplicate ATSDR MRLs, EPA IRIS, FDA This effort does not duplicate ATSDR MRLs, EPA IRIS, FDA
ADIs, Health Canada TDIs or RIVM TOCs.ADIs, Health Canada TDIs or RIVM TOCs.
To the contrary,To the contrary, ARA ARA shares resources to avoid duplication shares resources to avoid duplication because:because: It does not replace individual regulatory It does not replace individual regulatory
processes; processes; ARAARA users tap in as appropriate. users tap in as appropriate. Many risk values/issues will never be worked by Many risk values/issues will never be worked by
federal groups.federal groups. Current federal approaches have resource Current federal approaches have resource
limitations; thus, new chemicals addressed limitations; thus, new chemicals addressed without duplicate effort.without duplicate effort.
Update of older values can benefit federal groups Update of older values can benefit federal groups as one technical input to internal deliberations.as one technical input to internal deliberations.
ARAARA goes beyond risk values/issues – it is also a goes beyond risk values/issues – it is also a shared resource for training and data shared resource for training and data communication.communication.
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ARAARA Supports Existing Supports Existing Risk ValuesRisk Values
Provides guidance Provides guidance for sources of for sources of toxicity information toxicity information that may be used in that may be used in performing human performing human health risk health risk assessmentsassessments
ITERITER can can supplement existing supplement existing toxicity datatoxicity data
ARAARA can provide can provide Tier III valuesTier III values
EPA OSWER Directive 9285.7-53
32www.allianceforrisk.org
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SummarySummary
We are all committed to protecting We are all committed to protecting public health, although the issues are public health, although the issues are frequently complex they can often be frequently complex they can often be solved through collaborative solved through collaborative approaches (we’ll get farther faster).approaches (we’ll get farther faster).
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Collaboration is PowerfulCollaboration is Powerful
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Questions?Questions?