1. Identification and Deferral of Tissue Donors for Possible BSE/vCJ-D Exposure: Estimating the Impact Alan E. Williams, Ph.D. Director, Division of Blood Applications OBRR/CBER/FDA Presentation to FDA TSE Advisory Committee June 26, 2002

2. Overview Blood Donor Experience with vCJD Deferral Policy u Surveys of donor travel among geographically and demographically representative blood donor samples supported estimates of national impact (with many assumptions) u Estimates included: –Donor loss @ different “exposure” levels –Estimation of overall risk burden and portion of risk removed by different policy options

3. Residual vCJD Risk (Theoretical) vs. Percent of Blood Supply Lost

4. The 1999 Blood Donor Travel Survey: Methods u Random sample from 12/98 or 1/99 donors at twelve blood center sites u 19,067 anonymous OPSCAN surveys - single mailing + cover letter u 9,541 responses (~ 50%) u Travel, sex, age (5 strata), FT/Rpt, education (7 strata)

5. Advantages of surveys u In the setting of a well-defined sampling frame and experienced field sites, surveys are a well- established, reproducible data collection tool for blood donor populations u Blood donors generally provide favorable response rates. Anonymity factor is important u Wide scope of information (including demographics) can be collected simultaneously

6. Limitations of surveys u Findings reproducible, but difficult to validate u Some important sample subsets may be under- represented in the response u OMB approval necessary for data collection using Federal $$ u Matrix of multiple countries x multiple travel time frames = survey complexity

7. The 1999 Blood Donor Travel Survey: Travel Questions Did you live in the United Kingdom (England, Scotland, Wales, N. Ireland, Isle of Man, Channel Islands) or the Republic of Ireland between 1980-89/1990-96 ? If 30 days or less 1-3 days, 4-10 days, 11-30 days If less than one year 1-4 months, 5-8 months, 9-11 months If one year or more 1-2 years, 3-5 years, more than 5 years

8. Characteristics of the Tissue Donor Pool u Epidemiological characteristics are not well- defined compared to blood donors u Sites are generally not experienced in research data collection u Unless otherwise known, need to assume general population demographics (DMV data on organ donation relevant to tissue?)

9. Tissue Donor Populations - NOW………… -Musculoskeletal and skin n=20,000 (750,000 tissues) - Ocular (c ornea) n = 47,000 (includes 5,000 non-US) - FUTURE ….. -cord and peripheral stem cells, dura mater,semen, oocytes (Donor pool sizes/demographics unknown, except known age restrictions for semen and oocyte donors)

10. UK Travel Deferral Impact u Self deferral before blood drive (??) (media, letters to donors, recruitment screening, telephone inquiries) u Self-deferral at blood drive(??) (Donor educational material, Self-admin Qx) u Interview-based deferral * u Failure to appropriately defer ?? (False negative responses, incl. post-donation information)

11. UK Travel Deferral Impact u Self deferral before collection (??) (media, letters to donors, recruitment screening, telephone inquiries) u Self-deferral at collection(??) (Donor educational material, Self-admin Qx) u 2 o (or 1 o) Interview-based qualification –May need to address “don’t know” factor u Failure to identify disqualifying factor (False negative responses, may result in use of ineligible donor or result in post-donation information)

12. UK Travel Prevalence by Education among Blood Donors Education UK Travel <8 th grade0.9% 9-110.6% 12th0.5% HS grad5.4% Some college20.0% College grad37.2% Post grad36.3% Overall22.8% *Confounded by age. Education data not available for most blood/tissue donors

13. UK Travel Prevalence by Age among Blood Donors Age* UK Travel 17 - 2916.4% 30-3924.8% 40-5521.7% 56-6526.8% >6530.8% All ages22.8% *Confounded by other demographic variables

14. UK Travel Prevalence by Sex and FT/Repeat Status among Blood Donors Sex* UK Travel Male 23.4% Female 22.5% Overall 22.8% *Confounded by other demographic variables FT/Repeat*UK Travel FT 13.8% Repeat 23.0%

15. Assessment of Travel Deferral Impact among Tissue and Cell Donors u Survey mechanism to assess tissue donor loss may not be viable u Travel deferrals for FT blood donors at local blood center (with age adjustment) may reasonably predict travel characteristics of local tissue and cell donors (Alternately, the initial impact of vCJD deferral at local blood center may be used.)

16. Assessment of Travel Deferral Impact among Tissue and Cell Donors (cont.) u Well-designed pilot implementation programs can be used to identify both operational difficulties as well as predict tissue donor loss. u Innovative programs are being developed to “replace” donors lost to travel deferrals.

17. Rapid Response Blood Donor Data Network (Modified REDS Study Design) u 10-12 representative blood center sites u Capable donor/donation data systems (Blood collection,inventory,distribution) u Rapidly responsive to HHS data needs Rapid survey capability (OMB exemption, established IRBs, experienced staffing) u Private sector cost-sharing as needed to facilitate data collection (?)