1. The Role of the RAC in the Peer Review of CVM’s Risk Assessments Barry Hooberman, Ph.D., MPH Center for Veterinary Medicine Office of New Animal Drug Evaluation Rockville, MD 20855 September 30, 2003

2. 2 Risk Assessments at CVM Antimicrobial Resistance Human Food Safety Drug Residues Drug Residues Animal Feeds BSE BSE Contaminants (e.g., Dioxin) Contaminants (e.g., Dioxin)

3. 3 CVM’s Needs for Peer Review Common to all Risk Assessments Independent Review Independent Review Reviewers relationship with Agency Access to sufficient data/information Access to sufficient data/information Assess scientific reliability of data Assess scientific reliability of data Transparency/Openness Transparency/Openness Much in common with CFSAN and FSIS

4. 4 CVM’s Needs for Peer Review Distinct from CFSAN and FSIS Organization OrganizationSizeStructure Mission Mission New Drug Approvals Past Drug Approvals Subject Matter Subject Matter Antimicrobial Resistance Risk Assessment (ARRA) vs. Microbial Risk Assessment (MRA)

5. 5 Organization of RA Activities CFSAN:CVM: Risk Analysis Team Risk Analysis Team In the process of defining the boundaries between the assessors, managers, and communicators In the process of defining the boundaries between the assessors, managers, and communicators

6. 6 Risk Assessments and CVM’s Mission New drug approvals Guidance 152 Guidance 152 Review of past drug approvals Confidentiality restrictions may limit external peer review ARRA rely on publicly available information

7. 7 ARRA: Different from Microbial Risk Assessment Microbial and Antimicrobial Resistance Risk Assessments for food safety overlap extensively in terms of Microbiological properties of the hazard Microbiological properties of the hazard Exposure pathways – follow the movement of bacteria in the food chain Exposure pathways – follow the movement of bacteria in the food chain Consequences – e.g., human infections Consequences – e.g., human infections Key differences: The hazardous agents are resistance determinants The hazardous agents are resistance determinants Exposure – follow the movement of resistance determinants Exposure – follow the movement of resistance determinants Two separate pathways – direct and indirect Consequences - generally requires a human intervention to translate into adverse health risks. Consequences - generally requires a human intervention to translate into adverse health risks.

8. 8 Effects on RA Peer Review Relatively limited resources Efficient Allocation of resources for RA review Efficient Allocation of resources for RA review Regulatory considerations Use and availability of data for external review Use and availability of data for external review Use of risk assessment in the Center Use of risk assessment in the Center Different complexity of risk problem Less publicly available information on risk models Less publicly available information on risk models

9. 9 Options for Peer Review Internal review Not independent Not independent Sufficient access to data Sufficient access to data Skills available to assess scientific reliability Skills available to assess scientific reliability Not transparent Not transparent

10. 10 Options for Peer Review Inter-Agency review The Interagency Risk Assessment Consortium (RAC) The Interagency Risk Assessment Consortium (RAC) Semi-independent Semi-independent Potential for sufficient access to data/information Potential for sufficient access to data/information Able to assess scientific reliability Able to assess scientific reliability Not transparent, but has potential for transparency (Food Risk Clearinghouse) Not transparent, but has potential for transparency (Food Risk Clearinghouse)

11. 11 Options for Peer Review Public Meetings/Drafts of RA Independent Independent Sufficient access to data/information Sufficient access to data/information Range of skills in assessing scientific reliability of data Range of skills in assessing scientific reliability of data Transparent Transparent

12. 12 Options for Peer Review Outside Experts Range of independence Range of independence Used in planning, execution, and review of RAs Used solely for review Sufficient access to data/information Sufficient access to data/information Able to assess scientific reliability of data Able to assess scientific reliability of data Range of transparency Range of transparency

13. 13 Options for Peer Review Other The Courts The CourtsIndependent Sufficient access to data/information Varying skills to assess scientific reliability of data Transparent The problem of dueling experts! Resource intensive

14. 14 CVM’s Experiences with Peer Review Internal Review Limited capabilities Limited capabilities Inter-Agency Review RAC a very useful tool in the planning and execution of RAs RAC a very useful tool in the planning and execution of RAs RAC participation in CVM Public Meetings RAC participation in CVM Public Meetings RAC project: Practice of Microbiological Risk Assessment by U.S. Government Agencies RAC project: Practice of Microbiological Risk Assessment by U.S. Government Agencies EPA/OW funded Incorporates Agency experience that will be useful to RA peer reviewers of future microbial risk assessments

15. 15 CVM’s Experiences with Peer Review Public Meetings/Drafts Extensively used Extensively used Wide range of comments on all aspects of risk assessment and beyond Wide range of comments on all aspects of risk assessment and beyond Consultants/Outside experts Consultants/Outside experts Consultants/Outside experts Used in all phases in risk assessments Used in all phases in risk assessments Resource-driven Resource-driven Provide independent viewpoint Provide independent viewpoint

16. 16 CVM’s Experiences with Peer Review Lessons Learned Peer review is an important process that should be ongoing throughout the risk assessment Peer review is an important process that should be ongoing throughout the risk assessment A contentious risk assessment is independent of good peer review procedures A contentious risk assessment is independent of good peer review procedures

17. 17 Observations/Questions Resource allocation The consumption of peer review resources is inversely proportional to the level of risk (chasing zero risk). The consumption of peer review resources is inversely proportional to the level of risk (chasing zero risk). If the risk assessment finds the risk is from zero to very- nearly-zero, should we limit/control/attenuate scarce risk management resources on extensive peer reviews? The consumption of peer review resources is proportional to the uncertainty in the estimate of risk The consumption of peer review resources is proportional to the uncertainty in the estimate of risk A highly uncertain, high risk estimate report consumes fewer peer review resources than an equivalently uncertain low risk estimate report If contentiousness and length of reviews are driven by uncertainty, then these extremes in reported risk estimates should get the same level of peer review resources

18. 18 Observations/Questions Boundaries for determining level of Peer Review Based on magnitude (significance) of health effects, costs/benefits of risk management actions? Based on magnitude (significance) of health effects, costs/benefits of risk management actions? Use of outside experts in RA and peer review Questions of independence Questions of independence Relationship to Agency and regulated industry

19. 19 Acknowledgements H. Gregg Claycamp Mary Bartholomew