Title: GambroFenwal PASSPORT Post Marketing Study 7 Day Platelets Blood Products Advisory Committee Rockvil
1Gambro/Fenwal PASSPORT Post Marketing Study 7
Day Platelets Blood Products Advisory
CommitteeRockville, MDMay 1, 2008
- Larry J. Dumont, MBA, PhD
- Dartmouth-Hitchcock Medical Center
- Lebanon, New Hampshire
2Conflicts of Interest
- Consultant
- Gambro BCT
- bioMérieux
- BCSI
- Verax Biomedical
- Research support DHMC
- Cerus
- Fenwal
- Gambro BCT
- Haemonetics
- Immunetics
- Navigant Biotechnologies
- Verax Biomedical
- Travel Support
- FDA
3Important Facts!
- 7-day platelets are 510(k) cleared by FDA
- Gambro BCT, Inc.
- Fenwal, Inc.
- PASSPORT The post-marketing surveillance of
7-day platelets (a.k.a., Phase IV trial) - Not IND or IDE study as a prerequisite for
clearance - PASSPORT has
- An explicitly stated primary hypothesis with a
written analysis plan which was reviewed and
accepted by FDA - The planned analysis has not been conducted and
the primary hypothesis has not been tested
4Important Facts!
- Assumptions
- True contamination rate
- 178/M (1/5618) to 349/M (1/2865), based on one
bottle testing - The Release Test would detect at least 50
- Therefore, residual risk 100/M (1/10,000)
- This lead to the SAMPLE size calculation
- ? 4 positive out of 50K surveillance tests
- Upper 95 CL of no more than 1/5K (200/M)
residual risk - NB These risks are NOT weighted for the clinical
risk that may be presented by organism or day the
organism may be detectable.
5Important Facts!
- Assumptions
- True contamination rate
- 178/M (1/5618) to 349/M (1/2865), based on one
bottle testing - The Release Test would detect at least 50
- Therefore, residual risk 100/M (1/10,000)
- This lead to the SAMPLE size calculations
- ? 4 positive out of 50K surveillance tests
- Upper 95 CL of no more than 1/5K (200/M)
residual risk - NB These risks are NOT weighted for the clinical
risk that may be presented by organism or day the
organism may be detectable.
6SEPT 2003 7-day platelet function OK
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87-Day Platelet Release Test
- Sampling 24 - 36 h post apheresis collection
- 4-5 mL aliquots of SDP in both
- one aerobic and one anaerobic culture bottles
- Release if no growth indicated after 24 h on test
- Culture bottles remain on test until positive or
SDP expiry - Standard practices indicated for microbiology and
clinical follow-up for any positive cultures.
9PASSPORT - Post Marketing Surveillance
7-Day Apheresis Platelets
Tier 2
D1
Surveillance Test 2 bottle N 50,000
Release Test 2 bottle
Incubate
Incubate 7d
Data Analysis
10PRIMARY HYPOTHESIS
- 7 Day SDP when tested using the BTA Device and
Methods as described (i.e., at 24-36 hours post
collection, aerobic and anaerobic bottles) will
not present a greater risk of a detectable
bacterially contaminated platelet unit than 5 Day
SDP untested for bacterial contamination.
New endpoint for a modified study design
estimate residual bacterial risk for a 7 day old
platelet unit tested for bacteria on day 1.
Approve 7 day platelet storage if the bacterial
risk at day 7 is lower than the current bacterial
risk of untested platelet products. FDAs
Current Thinking on Bacterial Detection in
Platelets. ACBSA. August 27, 2004
11SPECIFIC AIMS
- Determine the Specificity, Sensitivity, Negative
Predictive Value, and Positive Predictive Value
of the 2-bottle Release Test. - Determine prevalence of bacterial contamination
for untested and for 2 bottle BTA tested SDP. - Determine performance contribution of the
anaerobic bottle to the BTA and assess the need
for anaerobic culturing in this application.
127 Day Platelet Adoption in the US
March
2008
33 organizations (51 centers) Participating
Nationwide
(5)
Implemented 7DP
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14Surveillance through 11 Feb 2008
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16Release Test
- Double product day 6 transfusions one
patient with fever CNS blood and unit - Double product day 4 transfusions STR 6-8h
post both pts staph aureus
AABB Bulletin 04-07, Oct 2004
17Surveillance Test
- 4369 tested after day 7
- 3 True Positives
- 686/M (95CI 142 2005)
- Unit 1 Staph Aureus, BPA 3.7h BPN 7.2h,
confirmed - Unit 2 Split donation Staph epi BPA 7.2h BPN
4.3h Second bag transfused on day 4 with no
adverse reaction reported - Unit 3 Strep veridans BPA 30.8h BPN 9.6h
confirmatory test diphtheroid like gram positive
rods
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193 / 4369
7 / 8282
6 / 6438
202-Bottle Results
based on clinical reports
21True Positive Both Bottles
22True Positive One Bottle Only
typically obligate anaerobe
23Clinical Outcomes
- 13 true positive, 202 indeterminate transfused
- No deaths Reported
- 14 transfusion reactions related to bacterial
contamination - 44/M (24-73)
24Clinical Outcomes - 1
25Clinical Outcomes - 2
26Clinical Outcomes - 3
27Summary
- 2-bottle Release Test
- True Positive 234/M (184-293)
- True Pos Indeterminate 1003/M (897-1118)
- Generally consistent with other reports
- 256 collections not interdicted prior to
transfusion - Surveillance
- 686/M (95CI 142 2005)
- Generally consistent with other reports
- No deaths reported
- Ness et al. 15/M
- 14 transfusion reactions
- 44/M (24-73)
- Ness et al. 70/M donations (49-105)
28Thank you!