1. FDA Workshop “Data and Data Needs to Advance Risk Assessment for Emerging Infectious Diseases for Blood and Blood Products” November 29, 2011, Gaithersburg MD Data Needed and Examples of Application in FDA Risk Assessments of Emerging Transfusion-Transmitted Diseases Hong Yang, Ph. D. Office of Biostatistics and Epidemiology, CBER, FDA

2. Outlines Important data needed for risk assessment (RA) for emerging transfusion-transmitted diseases Case study- vCJD RA Case study- Malaria RA

3. RA Model for Transfusion-Transmitted Infectious Diseases Recipient Risk (Probability infection) Blood Donation: (Probability infectious) Donor Risk (Probability infected) Disease prevalence Donor questionnaire screening Infection rate

4. Data needed for RA of Emerging Transfusion-Transmitted Diseases Disease prevalence – Blood testing for antigens (MSM RA) – Clinical case report (Malaria RA) – Biomarker prevalence (vCJD RA) – Donor characteristics-risk factors (vCJD RA) Efficiency of donor questionnaire screening – Information from existing deferral (vCJD, Malaria RAs) – Screening errors differ by targeted deferral Infection rate – Transfusion Look Back study (T. cruzi RA) – Animal data (vCJD RA) – Assuming 100% infection rate (Malaria RA)

5. Data for Estimation of Disease Prevalence among Donors (1) Blood testing for antigens –Most relevant –Likely unavailable for EID Application in FDA RA: Data on HIV and HBV prevalence in MSM population (MSM RA)

6. Data for Estimation of Disease Prevalence among Donors (2) Clinical case report –Under-estimate prevalence when incubation period of disease is long –Information lag for EID Application in FDA RA: CDC Malaria Surveillances Report (Malaria RA)

7. Data for Estimation of Disease Prevalence among Donors (3) Biomarker prevalence survey –A good surrogate ? Application in FDA RAs: UK tissue surveillance study (vCJD RA) Seroprevalence data (T. cruzi RA) normal brain vCJD florid plaque

8. Data for Estimation of Disease Prevalence among Donors (4) Donor characteristics-risk factors ─Travel survey Data from travel agency have limitation in scale and mode of transportation Donor data more relevant –Behavior survey Application in FDA RAs: Travel survey (vCJD and Malaria RAs) MSM behavior survey (MSM RA)

9. Data needed for RA of Emerging Transfusion-Transmitted Diseases Disease prevalence – Blood testing for antigens (MSM RA) – Clinical case report (Malaria RA) – Biomarker prevalence (vCJD RA) – Donor characteristics-risk factors (vCJD RA) Efficiency of donor questionnaire screening – Information from existing deferral (vCJD, Malaria RAs) – Screening errors differ by targeted deferral Infection rate – Transfusion Look Back study (T. cruzi RA) – Animal data (vCJD RA) – Assuming 100% infection rate (Malaria RA)

10. Data needed for RA of Emerging Transfusion-Transmitted Diseases Disease prevalence – Blood testing for antigens (MSM RA) – Clinical case report (Malaria RA) – Biomarker prevalence (vCJD RA) – Donor characteristics-risk factors (vCJD RA) Efficiency of donor questionnaire screening – Information from existing deferral (vCJD, Malaria RAs) – Screening errors differ by targeted deferral Infection rate – Transfusion Look Back study (T. cruzi RA) – Animal data (vCJD RA) – Assuming 100% infection rate (Malaria RA)

11. Case study 1 vCJD Risk Assessment for Plasma- Derived Blood Clotting Factors

12. Estimate of Donor Risk 12 Donor prevalence Donor’s travels to vCJD regions Donor questionnaire screening UK FranceEUMilitary Bases in EU vCJD prevalence in epidemic regions

13. Model Inputs (1) - Prevalence of vCJD in the UK 1.Epidemiological modeling vCJD clinical cases (LOWER estimate) FDA model estimated UK prevalence in 2002: ~4.5 per million 2.Tonsil/appendix tissue surveillance in UK patients (HIGHER estimate) Hilton, et al. 2004 1 in 4,225 individuals, or 237 per million 13

14. Donor Travel Survey –Blood Donor Travel Survey 1980-1996 (ARC 2000) Number donors traveled, destination, year, duration Efficiency of donor deferral –Assumed a mean 92% based on data for other diseases 14 Model Inputs (2) - Prevalence of vCJD in the US Donors

15. Case study 2 Malaria Risk Assessment

16. Estimate of Donor Risk 16 Number donors who traveled Donor questionnaire screening Donor prevalence Case incidence among travelers Infection prevalence among travelers

17. Input Data - Donor Risk for Malaria Annual number donor who travels to Malaria endemic areas (ARC 2007, personal communication) –Nationwide deferrals projected based on data collected in 6 blood centers Malaria incidence report (CDC 2001-2005) –Imported/acquired in US, US travelers/immigrants, regions of exposure, Plasmodium spp. Probability asymptomatic malaria (CDC 2001-2005) –<10% cases not showing symptoms after 90 days since exposure

18. Summary The most important data needed: disease prevalence, efficiency of donor questionnaire screening and infection rate Data contributed by blood centers and other stake holders has been essential for FDA RA We need more and better data

19. Acknowledgements FDA workshop working group –Anderson, Steven –Forshee, Richard –Gallagher, Lou –Walderhaug, Mark