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Partners i n Diagnost ics, LLCR eg u latory Consulting to Advance Global H ea lth
Elliot P. Cowan, PhDPrincipal
13817 Congress Drive Rockville, Maryland 20853-2632 USA
Tel: +1 [email protected]
PerformanceArt:DecidingonAcceptableSensitivityand
SpecificityforHIVSelfTests
ElliotP.Cowan,Ph.D.Principal,PartnersinDiagnostics,LLC
STAR“HIVSelfTesting- GoingtoScale”Workshop29March2017
Partners i n Diagnost ics, LLCR eg u latory Consulting to Advance Global H ea lth
Elliot P. Cowan, PhDPrincipal
13817 Congress Drive Rockville, Maryland 20853-2632 USA
Tel: +1 [email protected]
GoalsofthisTalk
2
• TodescribetheevolutionofthinkingthatledtotheapprovalbytheUSFoodandDrugAdministrationofthefirstover-thecounterhome-userapidHIVtest
• Toappreciatetheflexibilitythatcan(should?)beexercisedtomeetacriticalpublichealthneed
Partners i n Diagnost ics, LLCR eg u latory Consulting to Advance Global H ea lth
Elliot P. Cowan, PhDPrincipal
13817 Congress Drive Rockville, Maryland 20853-2632 USA
Tel: +1 [email protected]
AssessingHIVST
3
CONSISTENCY
AS HIGH AS POSSIBLE?
Partners i n Diagnost ics, LLCR eg u latory Consulting to Advance Global H ea lth
Elliot P. Cowan, PhDPrincipal
13817 Congress Drive Rockville, Maryland 20853-2632 USA
Tel: +1 [email protected]
Goal
Recognizingthatnotestis100%and100%specific,demonstratethatitissafeandeffective
foritsintendeduse
4
Partners i n Diagnost ics, LLCR eg u latory Consulting to Advance Global H ea lth
Elliot P. Cowan, PhDPrincipal
13817 Congress Drive Rockville, Maryland 20853-2632 USA
Tel: +1 [email protected]
HOWTHEUSFDAAPPROVEDANHIVST
5
Partners i n Diagnost ics, LLCR eg u latory Consulting to Advance Global H ea lth
Elliot P. Cowan, PhDPrincipal
13817 Congress Drive Rockville, Maryland 20853-2632 USA
Tel: +1 [email protected]
WhyHIVSTfortheUS?
HIV-infectedpeopleintheU.S.whodonotknowtheyareinfected
1in5
NumberofAmericansnewlydiagnosedwithHIVinfectioneachyear
~50,000
NumberofHIV-infectedpeopleintheU.S. 1.2MILLION
Source: US Centers for Disease Control and Prevention
Partners i n Diagnost ics, LLCR eg u latory Consulting to Advance Global H ea lth
Elliot P. Cowan, PhDPrincipal
13817 Congress Drive Rockville, Maryland 20853-2632 USA
Tel: +1 [email protected]
OraQuickÒ In-HomeHIVTestSystem
Partners i n Diagnost ics, LLCR eg u latory Consulting to Advance Global H ea lth
Elliot P. Cowan, PhDPrincipal
13817 Congress Drive Rockville, Maryland 20853-2632 USA
Tel: +1 [email protected]
ExpectedPerformance(FDABloodProductsAdvisoryCommittee)
• Professionalusetest:– Sensitivityandspecificity>98%asthelowerboundofthe95%confidenceinterval
• Selftest:– Sensitivityandspecificity>95%asthelowerboundofthe95%confidenceinterval
• Rationale:– Expecteddecreaseinperformanceinthehandsofnon-professionals
Partners i n Diagnost ics, LLCR eg u latory Consulting to Advance Global H ea lth
Elliot P. Cowan, PhDPrincipal
13817 Congress Drive Rockville, Maryland 20853-2632 USA
Tel: +1 [email protected]
Home-Use TestPerformanceasaMeasureofSafetyandEffectiveness
TEST PERFORMANCE SAFETY ANDEFFECTIVENESS
Partners i n Diagnost ics, LLCR eg u latory Consulting to Advance Global H ea lth
Elliot P. Cowan, PhDPrincipal
13817 Congress Drive Rockville, Maryland 20853-2632 USA
Tel: +1 [email protected]
ProfessionalTestPerformance(OraQuickADVANCE® HIV-1/2AntibodyTestwithOralFluidSpecimens:
PackageInsert)
Performance of the OraQuick ADVANCE® Rapid
HIV-1/2 Antibody Test(2-sided 95% CI)
BPAC Minimum Recommended Performance
Specificity 99. 8%(99.6 – 99.9%)
98% (lower bound of the 95% CI)
Sensitivity 99.3%(98.4 - 99.7%)
98% (lower bound of the 95% CI)
Partners i n Diagnost ics, LLCR eg u latory Consulting to Advance Global H ea lth
Elliot P. Cowan, PhDPrincipal
13817 Congress Drive Rockville, Maryland 20853-2632 USA
Tel: +1 [email protected]
Home-UseTestPerformance(OraQuick® In-HomeHIVTestforOralFluidSpecimens:Datashownat
BloodProductsAdvisoryCommittee,May2012)
Performance of the OraQuick® In-Home HIV Test Kit (2-sided 95% CI)
BPAC Minimum Recommended Performance
Specificity 99.98%(99.90 – 100%)
95% (lower bound of the 95% CI)
Sensitivity 92.98%(86.64 – 96.92%)
95% (lower bound of the 95% CI)
Partners i n Diagnost ics, LLCR eg u latory Consulting to Advance Global H ea lth
Elliot P. Cowan, PhDPrincipal
13817 Congress Drive Rockville, Maryland 20853-2632 USA
Tel: +1 [email protected]
Home-Use TestPerformanceasaMeasureofSafetyandEffectiveness
TEST PERFORMANCE SAFETY ANDEFFECTIVENESS
?
PUBLIC AND INDIVIDUALHEALTH IMPLICATIONS
RISKANALYSIS
Partners i n Diagnost ics, LLCR eg u latory Consulting to Advance Global H ea lth
Elliot P. Cowan, PhDPrincipal
13817 Congress Drive Rockville, Maryland 20853-2632 USA
Tel: +1 [email protected]
VeryHighLevelViewofFDA RiskAnalysis
• Estimatedtestresultsfornumbersofindividualsprojectedtobetestedannuallywhowouldnototherwisebetestedinthe1st year• Truepositive,falsenegative
• Truenegative,falsepositive
• Estimatednettransmissionsavertedinthe1st year
• Impactofswitchingfromprofessionaltestingtoself-testing
• Impactofwhowillusethetest
• Publichealthimplicationsandindividualhealthimplications
RISK MODEL
Partners i n Diagnost ics, LLCR eg u latory Consulting to Advance Global H ea lth
Elliot P. Cowan, PhDPrincipal
13817 Congress Drive Rockville, Maryland 20853-2632 USA
Tel: +1 [email protected]
FDA Projected Outcomes of Testing with the OraQuick® In-Home HIV Test in the 1st Year
(Based on sensitivity and specificity at the 95% confidence interval lower bound)
6 TP : 1 FN
770 TN :1 FP
True PositiveFalse Negative
True NegativeFalse Positive
42,0007,000
2,700,0003,600
(vs. 249:1)
(vs. 62:1)
Professional use test
From FDA presentation at Blood Products Advisory Committee, May 2012
Partners i n Diagnost ics, LLCR eg u latory Consulting to Advance Global H ea lth
Elliot P. Cowan, PhDPrincipal
13817 Congress Drive Rockville, Maryland 20853-2632 USA
Tel: +1 [email protected]
ProjectedNetTransmissionsAverted(CombinedProfessionalandHomeTesting)
44 7344 23
43 4 1
4 17 5
1 0
2 5
5 0
1 0 0
% S
wit
ch
ing
to
Ho
me
-Us
e T
es
tin
g
20 0 0 30 0 0 4 0 00 5 00 0 60 0 0 7 00 0Pred icte d Ne t Ave rted H IV Tra nsm ission s
5 th to 9 5 th Pe rce ntile M e an Tra nsm ission s Ave rte d
Pred icted Net A ve rte d H IV T ra ns m issio nsby P ercen t S w itch ing to Ho m e-us e Te sts
About300fewertransmissionsavertedifallcurrentusersofprofessionaltestsswitchtohomeusetests
FromFDApresentationatBloodProductsAdvisoryCommittee,May2012
Partners i n Diagnost ics, LLCR eg u latory Consulting to Advance Global H ea lth
Elliot P. Cowan, PhDPrincipal
13817 Congress Drive Rockville, Maryland 20853-2632 USA
Tel: +1 [email protected]
SummaryofFDAAssessment
• Basedonariskassessmentmodel,FDAprojectedanetpublichealthbenefittotheOraQuick® In-HomeHIVTest– NetincreaseinnumberofHIVinfectionsnewlyidentifiedinthefirstyear
– Nettransmissionsaverted• Individualriskremainsintheformofincreasednumbersoffalsenegativeresults
Partners i n Diagnost ics, LLCR eg u latory Consulting to Advance Global H ea lth
Elliot P. Cowan, PhDPrincipal
13817 Congress Drive Rockville, Maryland 20853-2632 USA
Tel: +1 [email protected]
MessagestoMitigateRisk• Apositiveresultwiththistestdoesnotmeanthatyou
aredefinitelyinfectedwithHIV,butratherthatadditionaltestingshouldbedoneinamedicalsetting.
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• AnegativeresultwiththistestdoesnotmeanthatyouaredefinitelynotinfectedwithHIV,particularlywhenexposuremayhavebeenwithinthepreviousthreemonths.
• RetestingisrecommendedifyoutestnegativeandcontinuetoengageinbehaviorthatputsyouatriskforHIVinfection.
• AnegativeresultdoesnotmeanitissafetoengageinriskbehaviorforHIVinfection.
Partners i n Diagnost ics, LLCR eg u latory Consulting to Advance Global H ea lth
Elliot P. Cowan, PhDPrincipal
13817 Congress Drive Rockville, Maryland 20853-2632 USA
Tel: +1 [email protected]
GeneralizingtheApproach:PracticalConsiderationsforSTAR
• TheresultsoftheriskmodelingdonefortheUSpopulationdonotnecessarilycarryovertoSTAR
• Requiresitsownsetofinputs
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Partners i n Diagnost ics, LLCR eg u latory Consulting to Advance Global H ea lth
Elliot P. Cowan, PhDPrincipal
13817 Congress Drive Rockville, Maryland 20853-2632 USA
Tel: +1 [email protected]
Challenges
• Wheredoyoudrawthelinebetweenacceptableandnotacceptable?
• Monitoringtodetermineiftherightchoicesweremade
Partners i n Diagnost ics, LLCR eg u latory Consulting to Advance Global H ea lth
Elliot P. Cowan, PhDPrincipal
13817 Congress Drive Rockville, Maryland 20853-2632 USA
Tel: +1 [email protected]
PotentialPitfalls
Partners i n Diagnost ics, LLCR eg u latory Consulting to Advance Global H ea lth
Elliot P. Cowan, PhDPrincipal
13817 Congress Drive Rockville, Maryland 20853-2632 USA
Tel: +1 [email protected]
ConcludingMessages
• Beflexibletomeetthedefinedpublichealthneed.
• Berationalinyourdecision-making.• Consideringbenefitsandrisksmaytakeyouindirectionsyoudon’texpect,butsometimeswhat’snotexpectedisagoodthing.
• Bewillingtoacceptrisks,butalsoacknowledgethemandmitigatethemasmuchaspossible.
Partners i n Diagnost ics, LLCR eg u latory Consulting to Advance Global H ea lth
Elliot P. Cowan, PhDPrincipal
13817 Congress Drive Rockville, Maryland 20853-2632 USA
Tel: +1 [email protected]
THANKYOU!
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