1. www.militaryblood.dod.milUNCLASSIFIEDwww.militaryblood.dod.milUNCLASSIFIED Evaluation of Rapid Screening Methods for Emergency Blood Collections CPT Robert Gates, USA Armed Services Blood Program Update 12 February 2008

2. www.militaryblood.dod.milUNCLASSIFIEDwww.militaryblood.dod.milUNCLASSIFIED Goal and Objectives Goal and Objectives Background Background Biokit evaluation Biokit evaluation Conclusion Conclusion Other Tests-preliminary results (RV 236) Other Tests-preliminary results (RV 236) Agenda

3. www.militaryblood.dod.milUNCLASSIFIEDwww.militaryblood.dod.milUNCLASSIFIED Goal Minimize TTD risk related to transfusion of freshly collected blood products in theatre

4. www.militaryblood.dod.milUNCLASSIFIEDwww.militaryblood.dod.milUNCLASSIFIED Objectives Rigorously evaluate the HCV and HBsAg rapid tests currently in use in theatre Assess all other candidate tests for future use

5. www.militaryblood.dod.milUNCLASSIFIEDwww.militaryblood.dod.milUNCLASSIFIED Background >250 freshly collected blood products are transfused into patients at US medical installations in OIF/OEF monthly Questionnaires and screening are either not performed or conducted in substandard fashion HIV, HCV, and HBV are rare but present in donors Rapid testing offers opportunity to mitigate risk

6. www.militaryblood.dod.milUNCLASSIFIEDwww.militaryblood.dod.milUNCLASSIFIED Biorapid Evaluation

7. www.militaryblood.dod.milUNCLASSIFIEDwww.militaryblood.dod.milUNCLASSIFIED Biorapid Evaluation Kit Insert Data Biorapid HCVBiorapid HBsAg Sensitivity.994 (.969-.999) (N=176) “able to detect HBsAg concentrations of 5IU/ml or higher” Specificity.987 (.973-.995) (N=472) “>98% in studies with blood donors’ samples” Storage Temp. 2-25  C2-8  C Testing Temp.“Room Temp.” Sample TypesS, P, WBS, P Volume Needed25µl125µl

8. www.militaryblood.dod.milUNCLASSIFIEDwww.militaryblood.dod.milUNCLASSIFIED Biorapid Evaluation Gold Standard EIA +- Biorapid HCV +90 -2313 3213 Aggregate data from: WWHV301 PHV106 PHW804 Sensitivity =.281 (.138-.468) Negative Likelihood Ratio (LR-) =.719 Specificity = 13/13 = 1.00 (.794-1.00)

9. www.militaryblood.dod.milUNCLASSIFIEDwww.militaryblood.dod.milUNCLASSIFIED Biorapid Evaluation Gold Standard EIA +- Biorapid HBsAg +80 -438 518 Aggregate data from: PHA106 PHA206 PHA808 Sensitivity =.157 (.070-.286) Negative Likelihood Ratio (LR - ) =.843 Specificity = 8/8 = 1.00 (.688-1.00)

10. www.militaryblood.dod.milUNCLASSIFIEDwww.militaryblood.dod.milUNCLASSIFIED HCV HBV

11. www.militaryblood.dod.milUNCLASSIFIEDwww.militaryblood.dod.milUNCLASSIFIED Biorapid Evaluation Gold Standard EIA +- Biorapid HCV+420 -850 Aggregate data from: American Red Cross samples Roberson Donor Center samples Sensitivity =.84 (.709-.928) Negative Likelihood Ratio (LR-) =.16 Specificity = 13/13 = 1.00 (.929-1.00)

12. www.militaryblood.dod.milUNCLASSIFIEDwww.militaryblood.dod.milUNCLASSIFIED Biorapid Evaluation Gold Standard EIA +- Biorapid HBsAg +350 -542 4042 Aggregate data from: American Red Cross samples Roberson Donor Center samples Sensitivity =.875 (.730-.889) Negative Likelihood Ratio (LR - ) =.125 Specificity = 8/8 = 1.00 (.916-1.00) * 18 Invalid tests

13. www.militaryblood.dod.milUNCLASSIFIEDwww.militaryblood.dod.milUNCLASSIFIED Conclusions Biorapid Evaluation Biorapid preformed poorly against panel specimens, but had no invalid results Also poor against clinical samples (84% sensitivity for HCV, 87.5% sensitivity for HBsAg) and had an 18% invalid rate with the HBsAg test Conclusion: Biorapid hepatitis rapid tests should be replaced by tests that perform better

14. www.militaryblood.dod.milUNCLASSIFIEDwww.militaryblood.dod.milUNCLASSIFIED RV 236 Seeks to identify best rapid assays for HCV and HBsAg Tests selected based on published material, paring down from 30 HBsAg, and 29 HCV to 6 HCV and 4 HBsAg Positive plasma down selection (N=50 per test) complete Selected tests will be challenged in three stages: -commercial panels (N = 54) -clinical samples (N = 672) -whole blood spiked with reactive plasma (N = 168) Ease of Use Survey

15. www.militaryblood.dod.milUNCLASSIFIEDwww.militaryblood.dod.milUNCLASSIFIED

16. www.militaryblood.dod.milUNCLASSIFIEDwww.militaryblood.dod.milUNCLASSIFIED * Sensitivity statistically superior Compared to Biorapid * * * *

17. www.militaryblood.dod.milUNCLASSIFIEDwww.militaryblood.dod.milUNCLASSIFIED HCV Test Invalid Rate

18. www.militaryblood.dod.milUNCLASSIFIEDwww.militaryblood.dod.milUNCLASSIFIED EOU Breakdown (HCV)

19. www.militaryblood.dod.milUNCLASSIFIEDwww.militaryblood.dod.milUNCLASSIFIED EOU Breakdown (HCV)

20. www.militaryblood.dod.milUNCLASSIFIEDwww.militaryblood.dod.milUNCLASSIFIED EOU Breakdown (HCV)

21. www.militaryblood.dod.milUNCLASSIFIEDwww.militaryblood.dod.milUNCLASSIFIED EOU Breakdown (HCV)

22. www.militaryblood.dod.milUNCLASSIFIEDwww.militaryblood.dod.milUNCLASSIFIED DOWN SELECTION TEST DATA (HCV) Rapid AssayObserved Sensitivity (%), 95% CI * Thermo stability (  C) Overall Ease of Use Run Time (Minutes) OraSure(OraQuick)100, 94.2-100.Up to 30520 AT FIRST (FIRST VUE)100, 94.2-1004-30410 ALFA (Instant View)100, 94.2-10015-30410 Axiom (axiom HCV)98, 89.4-99.92-30410 Core (Core HCV)98, 89.4-99.94- 30315 MedMira (MiraWell)100**, 93.3-1002-3023 Biokit (Biorapid)84, 70.9-92.8 2-25  C/RT N/A15 *Sensitivity based on small sample group (n=50),** 7/50 invalids (14%)

23. www.militaryblood.dod.milUNCLASSIFIEDwww.militaryblood.dod.milUNCLASSIFIED

24. www.militaryblood.dod.milUNCLASSIFIEDwww.militaryblood.dod.milUNCLASSIFIED

25. www.militaryblood.dod.milUNCLASSIFIEDwww.militaryblood.dod.milUNCLASSIFIED HBsAg Test Invalid Rate

26. www.militaryblood.dod.milUNCLASSIFIEDwww.militaryblood.dod.milUNCLASSIFIED EOU Breakdown (HBsAg)

27. www.militaryblood.dod.milUNCLASSIFIEDwww.militaryblood.dod.milUNCLASSIFIED EOU Breakdown (HBsAg)

28. www.militaryblood.dod.milUNCLASSIFIEDwww.militaryblood.dod.milUNCLASSIFIED EOU Breakdown (HBsAg)

29. www.militaryblood.dod.milUNCLASSIFIEDwww.militaryblood.dod.milUNCLASSIFIED EOU Breakdown (HBsAg)

30. www.militaryblood.dod.milUNCLASSIFIEDwww.militaryblood.dod.milUNCLASSIFIED PRELIMINARY DOWN SELECTION TEST DATA (HBsAg) Rapid AssayObserved Sensitivity (%), 95% CI * Thermo stability (  C) Overall Ease of Use Run Time (Minutes) AT FIRST (FIRST VUE)92,80.8-97.84-30515 Axiom (Axiom HBsAg)84**,70.3-92.72-30415 Core (Core HBsAg)90,78.2-96.74-30415 MINERVA98***,88.7-99.915-34415 Biokit (Biorapid)*87.5****, 73-88.92-8/RTN/A15 *Sensitivity based on small sample group (n=50),** 1/50 invalid (2%),***3/50 invalid (6%),****18/100 invalid (18% based on n=100)

31. www.militaryblood.dod.milUNCLASSIFIEDwww.militaryblood.dod.milUNCLASSIFIED Questions

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