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

Outlines

• Important data needed for risk assessment (RA) for emerging transfusion-transmitted diseases

• Case study- vCJD RA

• Case study- Malaria RA

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

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)

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)

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)

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

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)

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)

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)

Case study 1

vCJD Risk Assessment for Plasma-Derived Blood Clotting Factors

Estimate of Donor Risk

12

Donorprevalence

Donor’s travels to

vCJD regions

Donor questionnaire

screening

UK

France EU Military Bases in EU

vCJD prevalence in epidemic regions

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

• 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

Case study 2

Malaria Risk Assessment

Estimate of Donor Risk

16

Number donors who traveled

Donor questionnaire

screening

Donor prevalence

Case incidence among travelers

Infection prevalence among travelers

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

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

Acknowledgements

• FDA workshop working group– Anderson, Steven– Forshee, Richard– Gallagher, Lou– Walderhaug, Mark