Evaluation of Rapid Screening Methods for Emergency Blood Collections

www.militaryblood.dod.mil UNCLASSIFIEDwww.militaryblood.dod.mil UNCLASSIFIED

Evaluation of Rapid Screening Methods for Emergency

Blood Collections

CPT Robert Gates, USACPT Robert Gates, USAArmed Services Blood Program Update Armed Services Blood Program Update

12 February 200812 February 2008


• Goal and ObjectivesGoal and Objectives• BackgroundBackground• Biokit evaluationBiokit evaluation• ConclusionConclusion• Other Tests-preliminary results (RV 236)Other Tests-preliminary results (RV 236)

Agenda


Goal

Minimize TTD risk related to transfusion of Minimize TTD risk related to transfusion of freshly collected blood products in theatrefreshly collected blood products in theatre


Objectives

• Rigorously evaluate the HCV and HBsAg rapid tests currently in use in theatre

• Assess all other candidate tests for future use


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


Biorapid Evaluation


Biorapid EvaluationKit Insert Data

Biorapid HCV Biorapid 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. 2-25C 2-8CTesting Temp. “Room Temp.” “Room Temp.”

Sample Types S, P, WB S, P

Volume Needed 25µl 125µl


Biorapid Evaluation

Gold Standard EIA

+ -

Biorapid HCV

+ 9 0

- 23 13

32 13

Aggregate data from:WWHV301PHV106PHW804

Sensitivity = .281 (.138-.468)

Negative Likelihood Ratio (LR-) = .719

Specificity = 13/13 = 1.00 (.794-1.00)


Biorapid Evaluation

Gold Standard EIA

+ -

Biorapid HBsAg

+ 8 0

- 43 8

51 8

Aggregate data from:PHA106PHA206PHA808

Sensitivity = .157 (.070-.286)


Specificity = 8/8 = 1.00 (.688-1.00)


HCV HBV


Biorapid Evaluation

Gold Standard EIA

+ -

Biorapid HCV + 42 0

- 8 50

50 50

Aggregate data from:American Red Cross samplesRoberson Donor Centersamples

Sensitivity = .84 (.709-.928)


Specificity = 13/13 = 1.00 (.929-1.00)


Biorapid Evaluation Gold Standard EIA

+ -

Biorapid HBsAg

+ 35 0

- 5 42

40 42

Aggregate data from:

American Red Cross samples

Roberson Donor Center

samples

Sensitivity = .875 (.730-.889)


Specificity = 8/8 = 1.00 (.916-1.00)

* 18 Invalid tests


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


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


0102030405060708090

100

% Sensitivity

OraSure Alfa AT First Axiom CORE MedMira

Rapid test

Observed Sensitivity HCV Test


* Sensitivity statistically superior Compared to Biorapid

0102030405060708090

100

% Sensitivity

OraSure Alfa AT First Axiom CORE MedMira BIORAPID

Rapid Test

Observed Sensitivity

* * *

*


HCV Test Invalid Rate

0102030405060708090

100

% In

valid

Ora

Qu

ick

Alf

a

Axio

m

At

Fir

st

Co

re

Med

mir

a

Rapid Test

Observer 1

Observer 2


EOU Breakdown (HCV)

1

2

3

4

5

Score


Rapid kits

EOU HCV Reading


EOU Breakdown (HCV)

1

2

3

4

5

Score


Rapid kits

EOU HCV Interpreting


EOU Breakdown (HCV)

1

2

3

4

5

Score


Rapid Kits

EOU HCV Learning


EOU Breakdown (HCV)

1

2

3

4

5

Score


Rapid Kits

EOU HCV Overall


DOWN SELECTION TEST DATA (HCV)

Rapid Assay Observed Sensitivity (%), 95% CI *

Thermo stability (C)

Overall Ease of Use

Run Time (Minutes)

OraSure(OraQuick) 100, 94.2-100. Up to 30 5 20

AT FIRST (FIRST VUE) 100, 94.2-100 4-30 4 10

ALFA (Instant View) 100, 94.2-100 15-30 4 10

Axiom (axiom HCV) 98, 89.4-99.9 2-30 4 10

Core (Core HCV) 98, 89.4-99.9 4- 30 3 15

MedMira (MiraWell) 100**, 93.3-100 2-30 2 3

Biokit (Biorapid) 84, 70.9-92.8 2-25C/RT N/A 15

*Sensitivity based on small sample group (n=50),** 7/50 invalids (14%)


0

10

20

30

40

50

60

70

80

90

100

% Sensitivity

At First Axiom CORE Minerva

Rapid Test

Observed Sensitivity HBsAG Test


Observed Sensitivity

0102030405060708090

100

At First Axiom CORE Minerva BIORAPID

Rapid Test

% Sensitivity


HBsAg Test Invalid Rate

0102030405060708090

100

% In

valid

Min

erva

Co

re

Axi

om

At

Fir

st

Rapid Test

Observer 1

Observer 2


EOU Breakdown (HBsAg)

1

2

3

4

5

Score


Rapid Kits

EOU HBsAg Reading



0

1

2

3

4

5

Score


Rapid Kits

EOU HBsAg Interpreting



1

2

3

4

5

Score


Rapid Kits

EOU HBsAg Learning



1

2

3

4

5

Score


Rapid Kits

EOU HBsAg Overall


PRELIMINARY DOWN SELECTION TEST DATA (HBsAg)

Rapid Assay Observed Sensitivity (%), 95% CI *

Thermo stability (C)

Overall Ease of Use

Run Time (Minutes)

AT FIRST (FIRST VUE) 92,80.8-97.8 4-30 5 15

Axiom (Axiom HBsAg) 84**,70.3-92.7 2-30 4 15

Core (Core HBsAg) 90,78.2-96.7 4-30 4 15

MINERVA 98*** ,88.7-99.9 15-34 4 15

Biokit (Biorapid)* 87.5****, 73-88.9 2-8/RT N/A 15

*Sensitivity based on small sample group (n=50),** 1/50 invalid (2%),***3/50 invalid (6%),****18/100 invalid (18% based on n=100)


Questions


0

1

2

3

4

5

OraSure(OraQuick)

Alfa( Instantview)

AT First(FIRST VIEW)

Axiom CORE MedMira (MiraWell)

Test Kits

Ease of use survey (HCV)

QUESTION 4

QUESTION 5

QUESTION 6

QUESTION 9


0

1

2

3

4

5

AT First (FIRST VIEW) Axiom CORE Minerva (Vscan)

Test kits

Ease of use survey (HBsAg)

QUESTION 4QUESTION 5QUESTION 6QUESTION 9

Documents

Evaluation of Rapid Screening Methods for Emergency Blood Collections