Beyond Science and Decisions: From Problem Formulation to Dose-Response Assessment

 

Complete List of Case Studies


Workshop 9

Date: June 9-10, 2015
Location: University of Cincinnati, Cincinnati, Ohio

 

Overview

The workshop seeks to advance the recommendations of the NAS (2009) and subsequent framework of ARA (Meek et al., 2013) on problem formulation and dose-response analysis, through review of illustrative case studies for further development of risk methods.  This was the ninth workshop in an ongoing series hosted by the Alliance for Risk Assessment, engaging risk scientists from federal and state governments, industry, academia, consultative, and non-profit organizations.  Several talks and case studies were presented and reviewed by a panel of risk scientists, with a focus on adverse outcome pathways and a framework for evaluating risk from exposures to flame retardants.  Methods approved by the Science Panel will be integrated within the Dose-Response Framework, found at www.chemicalriskassessment.org.



Expand Workshop VIII - May 21-22, 2014, Austin, TX, Webinar
Expand Workshop VI - May 28-29, 2013, Arlington, VA, U.S. Environmental Protection Agency

May 28, 29, 30, 2013
Potomac Yard - Arlington, VA
In person & web participation available

Expand Workshop V - November 2, 2012, Webinar
Expand Workshop III - May 4, 5, & 6, 2011, Falls Church, Virginia; Noblis
Expand Workshop II - October 11-13, 2010, Crystal City, Virginia (In tandem with the Federal & State Risk Assessment & Toxicology Committee)
Expand Workshop I - March 16-18, 2010, Austin, Texas; Texas Commission on Environmental Quality



Background & Purpose:

The workshop series is continuing and expanding upon the discussion set forth by Science and Decisions: Advancement of Risk Assessment (NAS, 2009).  These meetings are conducted under the aegis of the Alliance for Risk Assessment (ARA), a broad-based non-profit, government and NGO coalition. The first phase of the workshop series was three workshops over the course of about a year.  The first workshop was held at the Texas Commission on Environmental Quality (TCEQ), Austin, Texas, and focused on brainstorming and selection of case studies illustrating various dose-response methods for different problem formulations.  A broad range of case studies proposed at the first workshop was then developed by workshop participants and discussed by the Science Panel at the second workshop, held in Crystal City, Virginia.  In considering the case studies, the Science Panel members provided input on the utility of the case study methods to address specific problem formulations, and identified areas for additional development.   The Science Panel and interested workshop participants developed an interactive framework (http://chemicalriskassessment.org/methods/)  for organizing case study methods, and the Panel used the framework to identify additional case studies that address important gaps in methodology; the third workshop (held at the Noblis facilities in Falls Church, Virginia) focused on these case studies and associated issues.  The framework references specific risk assessment methods, illustrated by case studies, and is intended for use by risk assessors and managers in a variety of settings (e.g., federal, state, and local agencies, industry).  It is based on the fundamental premise that the appropriate methodology for dose-response assessment is necessarily based on objectives specific to that application, including varying levels of analysis.  The framework has been revised since the initial development, and is currently available as a beta version of Framework 2.0.  A manuscript describing the framework and workshop process was published in 2013 and is available via open access .

The workshop series has transitioned to an “evergreen” approach, including a standing panel that reviews methods and issues on a semi-annual basis, leading to updating of the framework.  The standing panel was constituted in February 2012.  Core panel members serve for 2-3 years; members may be added to the standing panel to ensure expertise on specific topics.  Panel members were selected by the ARA Steering Committee to reflect a diversity of affiliations and areas of expertise, particularly biology/toxicology, risk assessment, and statistical/modeling. Under this evergreen approach, the workshop series is funded by organizations that desire technical feedback on the methods underlying case studies that might fit within the developing framework, from small grants to continue the development of the framework, and by donated time and in-kind resources.  In addition, the funding is anticipated to cover a limited number of case studies and/or methods papers on broader topics chosen by the science panel.  Panel members provide input on the utility of the case study methods to address specific problem formulations, and identify areas for additional development of the case study and/or method.  Inclusion of a method or case study in the framework as an illustration of a useful technique does not imply panel acceptance of the chemical-specific outcome.


Meek, M.E., M. Bolger, J.S. Bus, J. Christopher, R.B. Conolly, R.J. Lewis, G. Paoli, R. Schoeny, L.T. Haber, A.B. Rosenstein, M.L. Dourson. 2013.  A Framework for Fit-for-Purpose Dose Response Assessment. Regul. Toxicol. Pharmacol. 66(2):234-40.  Doi:  10.1016/j.yrtph.2013.03.012  Available at http://www.sciencedirect.com/science/article/pii/S0273230013000500

 

General Workshop Objectives:

  • Additionally develop the content of the NAS (2009) report on improving the risk assessment process to develop a compendium of practical, problem-driven approaches for “fit for purpose” risk assessments.  The compendium links methods with specific problem formulations (e.g., prioritization, screening, and in-depth assessment) for use by risk managers in a variety of types of organizations (e.g., local, regional and federal governments, private sector).   
  • Implement a multi-stakeholder approach to share information, ideas and techniques in support of developing practical problem-driven risk assessment methods compendium.

Specific Workshop Objectives:
  • Identify useful dose-response techniques for specific issues, including consideration of relevant data, 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 identified issue.
     
  • 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, as appropriate for the relevant risk assessment context.
     
  • Identify methods for calculating the probability of response for noncancer endpoints, as appropriate for the relevant risk assessment context.

  • Develop a risk methods compendium that will serve as a resource for regulators and scientists on key considerations for applying selected dose-response techniques for various problem formulations, with suggested techniques and resources.  
Roles

Steering Committee

The Alliance for Risk Assessment Steering Committee (ARA SC) provides oversight of the workshop series. The Steering Committee advises the DRAC on charge questions and has the final decision on members of the Science Panel after a review of all nominations.This project has been vetted by the Alliance for Risk Assessment (ARA) Steering Committee, which has representatives from tribal, state and federal government, academia and nonprofit (http://www.allianceforrisk.org/ARA_Steering_Committee.htm).


 

Science Panel & Nominations

The Panel provides input on case study methods being proposed to enhance the risk framework.   Panel members provide input on the utility of the case study methods to address specific problem formulations, and identify areas for additional development of the case study and/or method.  Inclusion of a method or case study in the framework as an illustration of a useful technique does not imply panel acceptance of the chemical-specific outcome. Core panel members will serve for 2-3 years; members may be added to the standing panel to ensure expertise on specific topics. Panel members are selected from a diversity of affiliations and areas of expertise, particularly biology/toxicology, risk assessment, and statistical/modeling.

Science Panel

Dose Response Advisory Committee (DRAC)

The workshop sponsors include state, federal, industry, and NGO representatives. The Dose-Response Advisory Committee has members of non-profit, state and federal government, including U.S. EPA, and industry.  The DRAC represents the various sponsors and has final decision in the development of workshop structure and charge questions, and the recruitment of presenters, after consultation with the ARA Steering Committee and Science Panel.

Link to sponsor organizations

Funding

The "Beyond Science and Decisions: From Problem Formulation to Dose Response" Alliance for Risk Assessment (ARA) project is funded through donations of money for travel, meeting expenses and contractor time, and by donated time. The distribution of donated money for the first 3 meetings in this series was 53%, 32%, and 14%, for industry, government and NGO groups, respectively; the distribution of donated time was roughly 33% for each sector. The distributions of time and money were different because many government and NGO groups were able to donate time, but not money.

The continuation of this project through the development of a standing science panel in meetings 4 and onward is envisioned to be based on donated money and time, as before. These resources are anticipated to come from different organizations that desire technical feedback on case studies that might fit within the developing framework, and from small grants to continue the development of the framework. In addition, this funding is anticipated to cover a limited number of case studies and/or methods papers on broader topics chosen by the science panel. In 2012, the distribution of grant money is anticipated to be 40%, 48%, and 13%, for industry, government and NGO groups, respectively. The distribution of donated time is anticipated to be similar across sectors.

Beyond Science & Decisions In the News

Ginsberg et al.  The NRC Silver Book: The Case for Improving Non-Cancer Risk Assessment. Guest Perspective.  Risk Policy Report 17 (37) Sept. 14, 2010 link

Hegstad M. Two Years On, Assessors Urge NAS to Clarify Advice on Linear Risk Method.  Guest Perspective.  Risk Policy Report 17(43). October 26, 2010. link

Hegstad M. Alliance Plans Panel To Address Key Scientific Issues In Risk Assessment. Risk Policy Report 18, (29). July 19, 2011 link

Hegstad M. EPA Framework Emphasizes Risk Management Options In Assessments Risk Policy Report 18(22). May 31, 2011. link

Meek B, Dourson M. Integrating Cancer and Non-Cancer Dose Response Assessment Approaches to Risk Assessment: The Role of Mode of Action. Risk Policy Report 17(39) September, 28, 2010 link

RASS August 2011 link

RSESS Winter 2011 link

RSESS Winter 2012 link

 

References

International Programme for Chemical Safety (2005) IPCS Framework for Analyzing the Relevance of a Cancer Mode of Action for Humans. http://www.who.int/ipcs/methods/harmonization/areas/cancer/en/index.html

National Academy of Sciences (2009). Science and Decisions: Advancing Risk Assessment (NAS Final Report). http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=202175

United States (2005). Guidelines for Carcinogen Risk Assessment. link

 

Scientific Society Presentations

Society for Risk Analysis 2010 Annual Meeting Presentations from the symposium on “Beyond Science and Decisions

2011 Society for Risk Analysis Symposium: Improving Problem Formulation and Dose-Response Beyond Science and Decisions

Sponsored by: Dose-Response Specialty Group
Co-Chairs: Julie Fitzpatrick, Rick Becker

Tox Forum 2012

Society of Toxicology 2012

Society for Risk Analysis - New England Chapter

Presentation at Society for Risk Analysis 2012

Presentation at Society for Risk Analysis 2014

 

*Fit for purpose: Consistent with the NRC (2009) report, this workshop defines “fit for purpose” as recognizing that the nature and extent of the assessment needs to be considered in the problem formulation stage, with level and complexity to be no greater than that needed to identify the best choice among risk management options. In practice, the workshop recognizes that this is accomplished by having a variety of available tools (e.g., tools for acute vs. chronic exposures) and using tiered approaches, proceeding down the tiering only as far as necessary to set an issue, exposure or chemical aside (as not of concern) or to target it for further assessment and/or management. 

Adapted from:  Meek, M.E., M. Bolger, J.S. Bus, J. Christopher, R.B. Conolly, R.J. Lewis, G. Paoli, R. Schoeny, L.T. Haber, A.B. Rosenstein, M.L. Dourson. 2013.  A Framework for Fit-for-Purpose Dose Response Assessment.  Manuscript in review

 

For more information, please contact Oliver Kroner.

 

 

 

Workshop Collaborators

SOT

Texas Commission on Environmental Quality

2

TERA


7

3

Noblis Logo

4    

IDEM Logo

6

5

Georgia
                                           
8

New Zealand Ministry of Health (Manatu Hauora)

9      
10

11

12


1

2

3

4

mpca-horiz-left

FDA, U S Food and Drug Administration

2

Department of Health

5

1

Ohio EPA logo

1

Texas Chem Council

NIPERA

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nctr

Summit

Environ

EPRI

ARASP

AICL