Use of Quantitative Risk Assessments in Blood Safety Regulation

1. Use of Quantitative Risk Assessments in Blood Safety Regulation Jay S. Epstein, M.D. Director, OBRR, CBER FDA Workshop on Data and Data Needs to Advance Risk Assessment for Emerging Infectious Diseases for Blood and Blood Products November 29, 2011 Gaithersburg, MD

2. Workshop Issue and Objectives • Issue: • To improve & expedite data generation and collection for conducting quantitative risk assessment of EIDs that could affect US blood safety • Objectives: • To gain insight and seek cooperation on • Development and execution of targeted donor questionnaires for emerging infectious diseases • Conducting and coordinating seroprevalence surveys for emerging infectious diseases

3. Concepts of Emerging and Reemerging Infectious Diseases (EIDs) - I Emerging infectious diseases are outbreaks of • Previously unknown diseases (e.g. AIDS, vCJD) • Known diseases whose incidence in humans has significantly increased in the past two decades (e.g. West Nile virus, babesiosis) • Prevalent diseases whose potential significance is newly recognized (e.g. Hepatitis C)

4. Concepts of Emerging and Reemerging Infectious Diseases (EIDs) - II Reemerging diseases are outbreaks of known diseases that have reappeared after a significant decline in incidence (e.g. dengue ) Deliberately emerging diseases are those that are intentionally introduced through acts of terrorism (e.g. anthrax) • Newly emerging, re-emerging, and deliberately emerging diseases are all treated in much the same way from a scientific and public health standpoint.

5. Emerging Infectious Diseases May Threaten Blood Safety - I • Numerous EIDs in the last three decades have raised sufficient blood safety concerns to warrant investigations and sometimes interventions (HIV, HCV, HHV-8, SARS, Lyme disease, monkey pox, simian foamy virus, WNV, babesiosis, dengue, chikungunya, pandemic influenza, Chagas disease, malaria, human parvovirus B19)

6. Emerging Infectious Diseases May Threaten Blood Safety - II • With each EID, core questions are asked relevant to blood safety: • Is the agent disease associated? • Is the agent infectious by the IV route of exposure? • Is it present in the blood of asymptomatic persons (either acutely or chronically)? • Does the agent survive in stored blood components? • What is the prevalence in blood donors? • Has the disease been observed in transfusion recipients? • Is it transmitted by transfusion (and with what efficiency)? • What is the disease attack rate in susceptible blood recipients? • Is there a feasible intervention (history screen or lab test)? • How serious is the disease? • Can the disease be diagnosed and treated? • In general safety decisions are made based on assessments of risk, often before definitive answers

7. Risk-Based Decision Making for EIDs - I • Risk based decision making for EIDs follows generally applicable principles of good policy making: • Decisions based on scientific, medical and epidemiological evidence • Consideration of economic, ethical and social dimensions • Efficacy and cost-effectiveness • Partnership and active participation by relevant stakeholders • Transparency • Effective Communication

8. Risk-Based Decision Making for EIDs - II Risk-based decision making for EIDs follows a structured process: • Situation analysis, definition of problem and risk identification • Identification of policy alternatives • Risk assessment and analysis • Identification of preferred policy option and policy formulation • Policy implementation • Monitoring and evaluation • Risk management Within this general framework the most critical elements are risk assessment and risk analysis

9. Risk-Based Decision Making for EIDs - III • Quantitative risk assessments (QRAs) enable FDA to estimate the risks and benefits of candidate blood safety interventions recognizing and including estimates of uncertainty. For this reason, QRAs have been used increasingly as part of FDA decision making for EIDs. • Recent examples have included: • Geographic deferrals for vCJD risk in Europe, • Risk of vCJD from plasma derived Factor VIII, • Uuniversal versus selective antibody testing for T. cruzi infection, • Policy considerations for malaria deferral related to exposures in Mexico and for geographically selective babesia testing • In most if not all cases, FDA has relied on critical data inputs from outside sources

10. Estimated risk of transmitting vCJD to US recipient of US plasma-derived factor VIII to recipient with severe Hemophilia A(probabilistic model: H Yang & S Anderson OBE with OBRR staff, CBER)

11. Benefit - Risk Analysis of Malaria Deferrals for Donors with Recent Travel to Mexico Numbers in parentheses are 5% to 95% confidence intervals. * Risk based on data from the REDS II and BSRI studies. ** Based on the annual collection of ~15 million blood units

12. FDA Model Predicted Average TTB cases in each State Based on Reporting of Babesiosis Cases in a CMS Dataset Model Assumptions - Asymptomatic carriers cause all TTB cases - Asymptomatic prevalence is fixed ratio to symptomatic incidence - One to one ratio of infected units to asymptomatic donors Conclusions - Model shows concordance (not identity) with observed data - 95% of all predicted TTB cases: NY, CT, MA, CA, NJ, MD, VA, FL, PA, RI, TX, MI, MN, WI, CO, NC, AZ, MO and GA - 95% of actual TTB cases are: RI, NY, CT, NJ, WI, MN, MA, IN, CA, MD, PA, FL, TX, OH, NH, VA and ME

13. Summary • QRAs play a central role in FDA decision making for blood safety, especially for threats from EIDs • FDA depends on outside sources to obtain critical data elements needed to construct meaningful QRAs • Identification of data sources and cooperation with outside parties are crucial • Estimates for exposure risk from transfusion often depend on donor histories (e.g. travel surveys) and prevalence studies • Your help is needed to assure good decision making for blood safety in the face of EIDs!