New and emerging diagnostic tests

for screening of infections during

pregnancy

March 2009

TheNationalHorizonScanningCentreResearchProgrammeispartofthe
NationalInstituteforHealthResearch

Acknowledgements
TheauthorwouldliketothanktheinternalreviewteamattheNationalHorizonScanningCentrefor
theirinputintoplanningandwritingthereport.Theauthorwouldalsoliketoextendtheirthanksto
theprojectexternaladvisors:ProfessorCatherinePeckham,InstituteofChildHealth,London,Dr
PennyWilson,TechnologyStrategyBoard,andDrJohnMarshall,NationalScreeningCommittee;and
expertsandorganisationscontactedduringthisreview.

TheNationalInstituteforHealthResearchsNationalHorizonScanningCentreResearchProgramme
isfundedbytheDepartmentofHealth.

TheviewsexpressedinthispublicationarethoseoftheauthorandnotnecessarilythoseoftheNHS,
theNIHRortheDepartmentofHealth

Copyright20102011UniversityofBirmingham.

Author: DrSaraTrevitt,SeniorHorizonAnalyst,NationalHorizonScanning
Centre


Customer: UKNationalScreeningCommittee


Reporteffectivefrom: 16thMarch2009

TheNationalHorizonScanningCentre
DepartmentofPublicHealth,EpidemiologyandBiostatistics
UniversityofBirmingham,Edgbaston,BirminghamB152TTEngland
www.nhschealthhorizons.org.uk

Introduction

Inearly2009,theNationalHorizonScanningCentre(NHSC)conductedareviewofnewand
emergingdiagnostictestsforthescreeningofinfectionsduringpregnancy,onbehalfofthe
UnitedKingdomNationalScreeningCommittee(UKNSC).

Currentantenatalscreeningpractice
Around 700,000 women become pregnant in the UK every year1. Under the National
Screening Programme, all women are offered testing for a range of maternal diseases,
includinganumberofinfectiousdiseases.AccordingtocurrentUKpractice,between812
weeksgestation,womenpresentingforantenatalcareareroutinelyofferedscreeningtests
for syphilis, Hepatitis B Virus (HBV), Human Immunodeficiency Virus (HIV) infection and
rubella susceptibility. Samples of blood are taken, generally at antenatal clinic visits, and
sentoffforanalysisatcentralisedlaboratories.Thetestresultscomebacktothepatients
record some days or weeks later, and are provided to the woman at her next clinic visit
(usuallythe20weekscan)ifnoissuesareidentified.Teststhatarepositiveoruncertainat
thisinitialscreeningstageareconfirmedbysubsequentdiagnostictestingandthepatient
recalledifnecessary.

Servicedeliveryissues
The current system of antenatal screening for infections can be inefficient for several
reasons:

a) sampling and testing take place in separate locations (clinic and laboratory
respectively), giving rise to the potential for samples and/or results to become
mislaid;
b) thesamplevolumetakenmaybeinsufficientforanalysis,requiringpatientrecall;
c) samplesmaybestoredincorrectly,invalidatingtheresults;
d) there may be problems with test accuracy (especially the occurrence of false
negativeresults)andqualityassurance(QA);
e) thereisconsiderablegeographicalvariationinpractice.

Pointofcaretesting
Pointofcare(POC)testing(alsoknownasnearpatienttesting),inwhichbothsamplingand
analysistakeplaceinaclinicorprimarycaresettingandtheresultsareavailablethenand
there,couldalleviatesomeoftheseservicedeliveryproblems.Atpresent,onlyahandfulof
POCtests(POCT)areinclinicaluseintheUK,predominantlyinsexuallytransmitteddisease
(STD) clinic and outreach settings. POC testing is not currently part of routine practice in
NHSantenatalclinics.Thisislargelyduetoconcernsovertestaccuracyandreliability,and
wellasresourceissuessuchasextracostsandstafftrainingrequirements,andreluctance
fromcentrallaboratories.

TheUKNSCisinterestedinknowingaboutanynewteststhatmaybecapableofproviding
rapidandaccurateresultsduringasingleroutineantenatalvisit,therebyavoidingtheneed

1
Source:NHSClinicalKnowledgeSummaries
http://www.cks.library.nhs.uk/patient_information_leaflet/antenatal_screeningaccessed12February2009

1
tosendsamplesawayinspaceandtimeforlaboratoryanalysis.Theadoptionofsucha
pointofcarescreeningstrategywithintheNHScouldoffersignificantadvantagesinservice
deliveryandpatientcare.

Clinicalissues
TheuseofrapidantenataltestingisofclinicalsignificanceforHIVandsyphilisinfection,as
measurescanbetakenimmediatelytopreventthebabybecomingaffected.Inthecaseof
HBV infection in the mother, precautions can be taken during delivery and the baby
vaccinatedafterbirth,andincasesofrubellathemothercanbeofferedtheMMRvaccine
after the baby is born to protect any future pregnancies. Although most testing for
infectionstakesplacebytheendofthefirsttrimester,womenathighriskforHIVpresent
for antenatal care as late as 18 weeks on average, and in these cases rapid testing is
particularlyimportant.

Currenttechnology
Rapiddiagnostictestsrelevanttothisreviewarebasedononeofthreeexistingmethods:

1. Particleagglutinationtests:thesearebasedonasimpleonestepantigen/antibody
reactionprocedurethatrequiresnospecialequipment,andtypicallyproduceresults
in1060minutes.

2. Immunoconcentration tests, also known as flow through devices. These typically

produceresultsin515minutes.

3. Immunochromatography assays using lateral flow strips. This is the most recent
technologicaldevelopment,andresultsaregenerallyavailablewithin20minutes.

InordertoselldiagnosticproductsforclinicaluseintheUnitedKingdom,companiesmust
obtain an indicationspecific CE marking2 for each product. HIV and Hepatitis B tests are
subjecttoparticularlystringentlicensingregulations,andforthisreasoncompaniestendto
be less proactive in this area of in vitro diagnostics (IVD)3. Unlike for pharmaceutical
products,thereisnocomprehensivedatabaseofdiagnosticproductsthatareCEmarked,so
informationonCEmarkingstatusmustbeobtaineddirectlyfromthecompanyconcerned.

Aims

The aim of this review is to identify new and emerging diagnostic screening technologies
thatmaybeofinteresttotheUKNSCinitsfutureplanningofantenatalscreeningservices
in the UK. The NHSC had four weeks (extended to six) in which to identify, research and
compileatablecontainingbasicinformationontechnologieswhichmetthereviewcriteria.

2
TheCE(ConformitEuropea)markisthedeclarationmadebythemanufacturerthataproductmeetsthe
requirementsintheIVDMedicalDevicesDirective(98/79/EC),necessaryfortheproducttobesoldlegallyin
theEuropeanUnion(EU).
3
Invitrodiagnostic(IVD)testsarecarriedoutonspecimensamplestakenfromthebody,e.g.blood,urineand
saliva,asopposedtotestingcarriedoutdirectlyonorinsidethebody.

2
Reviewcriteria

Diagnosticscreeningtechnologiesdevelopedbyselectedcompanies4thatare:

Indications for the routine detection of rubella susceptibility, and/or syphilis,

and/orHBVand/orHIVinfectionduringpregnancy.

Timeframe(i)upto18monthspriortoCEmarking,or(ii)CEmarkedbutcurrently
onlyinlimitedresearchuseintheUK(i.e.atonlyafewUKcentres)*.

Speed/efficiencyintendedtoprovideatimefromsamplingtoresults(turnaround
time, or TAT) of 2 hours or less and/or may confer significant improvements in
efficiencytothescreeningprocess,e.g.greatertestreliability.

*InpracticeitproveddifficulttoobtaininformationonhowwidelyusedtestswereintheUK,andas
asurrogateindicator,testswereincludediftheyhadbeenCEmarkedrecently(i.e.withinthelast12
months).

OfparticularinteresttotheUKNSCwasintelligenceonemergingcombinationrapidPOC
testscapableofperformingmultiplextesting(i.e.abletorunrelatedtestsinparallelona
singleintegratedsystem)forsyphilis,HBVandHIVinanantenatalclinicsetting.

Methods

Thecentralstrategyofthereviewwastoidentifycompaniesactiveinthisfieldofinvitro
diagnostics, and to interrogate their websites and contact them directly to obtain
information on their relevant new and emerging products. The review criteria were then
applied to the technologies identified, in order to create a table of those that met the
criteria.Thisprocesswasconductedinfoursteps.

Step1:identificationofactivecompanies
ThefirststepwastocompilealistofrelevantexistingrapidPOCtests,inordertoidentify
those companies that are producing them and may therefore have relevant tests in
development.Thiswasdoneintwoways:

1.1 Intelligence on relevant technologies and companies active in this field was sought
throughdirectcommunicationswith:
a) individualPOCTexperts
b) professionalorganisations,suchastheRoyalCollegeofPathologists
c) IVDtradeassociationsintheUKandEurope.

Emails were sent to enquire if these individuals and organisations were aware of any
relevant tests or could suggest any companies that might be developing such tests.
Experts and organisations that didnot respond werecontacted at least twice more. A

4
FourcompanieswerenotincludedintheNHSCreview:InvernessMedical,Philips,RocheDiagnosticsandGE
Healthcare,sincetheirproductsweretobeinvestigatedbyDrPennyWilsonoftheTechnologyStrategyBoard.

3
 fulllistoforganisationsandindividualexpertsapproached,andtheemailssenttothem,
areatAnnex1.

1.2 Online sources (listed at Annex 2) were searched using predetermined search terms
(listed at Annex 3) to identify relevant tests (both existing and in development) and
activecompanies.Thesesourcesincluded:
a) diagnosticproductlistings
b) technology databases of horizon scanning and health technology assessment
organisations
c) licensingorganisationsoutsidetheEU:listofproductsapprovedbytheUnitedStates
(US)FoodandDrugsAdministration(FDA)
d) clinicaltrialdatabasesofongoingresearchofinvestigationalproducts
e) Medline,CochranelibraryandGoogle.

Step2:researchingcompanyportfolios
Once a list of potentially relevant companies had been drawn up we researched their
product portfolios by examining their websites for technical information and pipeline
intelligence.Anyrelevantinformationontechnologiesthatmayfitanyofthereviewcriteria
wasidentified.

Step3:companyengagement
Those companies who appeared to have relevant products and/or seemed likely to have
active development pipelines were contacted by email to enquire if they had any tests
relevanttothereview.Companiesthatdidnotrespondwerecontactedatleastthreetimes
intotal.

Step4:compilingatechnologytable
Product information obtained from company websites (Step 2) and company
correspondence(Step3)wasusedtoprogressivelypopulateatableoftechnologies.Step2
was an iterative process because most of the companies needed to be contacted several
timestoobtaininformationrequiredforfilteringagainstthereviewcriteria(e.g.theTAT,CE
status/plans,andsuitabilityforPOCdiagnosticscreeninguse).

Step5:filtrationoftechnologies
Thereviewcriteriawereappliedtothetechnologiesidentified.TobeclassifiedasPOC,tests
wereeitherdescribedassuchincompanyliteratureorbeconfirmedasbeingsuchbythe
company through direct correspondence. Some tests could be eliminated with certainty if
oneormoreofthecriteriaweredefinitelynotmet,forexampleifthecompanyconfirmed
that the test was not for POC use, or was intended for blood screening rather than
diagnosticscreening.

Theremainingtechnologiesweredividedintotwogroups.Thosethatfullymetthereview
criteria were placed on an AList. Those that met some but not all of the criteria were
placedonaBList,ifinformationontheunmetcriteriawasunavailable(e.g.thecompany
didnotreplywithrequiredinformation).

4
Results

During the period of the review, three of the six experts approached responded to our
requestforinformation,asdidfouroftheeightprofessionalorganisations,andoneofthe
fivetradeassociations.

We identified 39 potentially active companies (Table 1). Thirtyone responded to our

requestsforinformationandeightdidnot,despitechasing.

Table1.Companiesidentifiedandcontacted

Companyname
AbbottDiagnostics
BeckmanCoulter
BiokitSA
BioLyticalLaboratories
BioRadLaboratories
Bioscience
CalypteBiomedicalCorporation
CambridgeBioScience
ChemBioDiagnosticSystemsInc
ChemtronBiotechInc
CTKBiotechInc
DiaSorinSpA
DiesseDiagnostica
FINDDiagnostics(FoundationforInnovativeNewDiagnostics)
FujirebioDiagnosticsInc(akaFDI)
GenProbeInc
HealthcareProvidersDirectInc
HumanDiagnosticsWorldwide(akaHumanGmBH)
INDDiagnosticsInc(InternationalNewtechDevelopment)
InnoGenetics
InTecProductsInc
IQuumInc
JMitra&CoPvtLtd(EmbeeDiagnostics)
LobeckMedicalLtd
LumiQuick
MedMiraLaboratoriesInc
MPBiomedicalsLLC(subsidiary=GenelabsDiagnosticsLtd)
NovartisVaccinesandDiagnosticsInc
OmegaDiagnosticsLtd
OraSureTechnologiesInc
Orgenics(brandnameofInvernessMedicalInnovations)
OrthoClinicalDiagnostics(J&J)/Veridex
QualproDiagnostics(TulipGroup)
RandoxLaboratoriesLtd
RocheDiagnostics
SiemensHealthcareDiagnostics
SpanDiagnosticsInc
StandardDiagnosticsInc
TrinityBioTechplc

5

Seventyseventechnologieswereidentified,ofwhich34didnotmeetoneormorereview
criteriaandwereeliminated.Theremaining43technologieswerefilteredaccordingtothe
reviewcriteriaintotwogroups:

1. AList:31technologiesthatmetallofthereviewcriteria(Table2)

Disease AListtechnologies (seeTable2 fordetails)

HIV 11
HBV 5
Syphilis 10
Rubella 2
Combined/multiplex 3
Total 31

TheAListincludedthreeemergingcombinationtests(alsoknownasmultiplextests):

a) INST HIV1/2 & Syphilis (60 second) Combo Rapid test from BioLytical Laboratories
(CEmarkingDecember2009)
b) MultiploRapidHBV/HIV/HCVAntibodytestfromMedMiraLaboratories(CEmarking
imminent)
c) QuickProfile Blood Screen Panel (HIV/HBsAg/Syphilis) from LumiQuick (fully
developedbutCEplansundecided).

2. BList: 12 technologies that met most of the review criteria, but for which some key
informationwasnotforthcomingfromthecompany(Table3).

Disease BListtechnologies (seeTable3 fordetails)

HIV 4
HBV 2
Syphilis 3
Rubella 3
Combined/multiplex 0
Total 12

Table 4 shows three further technologies that did not meet the review criteria but might
nonethelessbeofinteresttotheNSC.

6
Table2.AListtechnologies(commerciallysensitiveinformationhasbeenremoved)

Disease Testname Company Descriptionandcost Settingforuse Sampletype Timeto CEmarking/
results availability

HIV INSTIHIV BioLyticalLaboratories Rapidinvitroqualitativeflow Pointofcare, Wholeblood(50 60seconds CEmarked(2006)
1/HIV2 http://www.biolytical.c throughtestforthedetectionof inc.antenatal gcapillary andavailable,butnot
AntibodyTest om antibodiestoHIVType1and2 clinic.Canbe blood),serumor yetinroutineusein
performedbya plasma theUK
Cost:inEuropeUSD$710pertest nurse/trained
personnel Researchongoing5
HIV MiraCareRapid MedMiraLaboratories Flowthroughdevice.Singleuse Pointofcareor 1dropofwhole 3minutes CEmarkedand
HIVAntibody http://www.medmira.c qualitativeimmunoassaytodetect nearpatient blood,serumand availableinpartsof
Test. om antibodiestoHIVtype1and2. settings plasma theEU:Spain,
Portugal,Germany,
Romania+Greece.
Notyetbeingsoldin
theUK
HIV CapillusHIV TrinityBioTechplc Rapidqualitativeassaybasedon Initialscreening Wholeblood, 37minutes Availablebutnot
1/HIV2 http://www.trinitybiot latexaggregation,forthe inlowvolume plasmaand (aftersome widelyusedintheUK
ech.com detectionofantibodiestoHIV1 testingfacilities serum manual
and2.Somemanualpreparation andin preparatory
andadditionalequipmentrequired emergency steps)
situations
HIV HexagonHIV HumanDiagnostics Immunochromatographicrapid Pointofcare Wholeblood, 520 RecentlyCEmarked
Worldwide testforantibodiesagainstHIV1 serum,plasma minutes andavailable
http://www.human.de and2(3rdgeneration)
HIV SDBiolineHIV StandardDiagnostics Immunochromatographicrapid Wholeblood(20 520 CEmarkedOct2008
1/23.0 Inc testforthequalitativedetectionof g),plasmaand minutes andavailable
http://www.standardia anitbodiestoallisotopesspecific serum(both10
.com toHIV1and2. gneeded)
HIV SignalHIVtest SpanDiagnosticsLtd Rapidscreeningtest,basedon Pointofcare Serumand 10minutes

5
PhaseIIItrialintheUnitedStatesstartedJuly2007(n=2,500),comparingreliabilityandaccuracywithexistingstandard.Seehttp://clinical
trials.gov/ct2/show/record/NCT00514605fordetails

7
 http://www.span.co.in lateralflowimmunochromato plasma (aftersome
graphy,fortheearlyqualitative manual
detectionofantibodiestoHIV1 preparatory
and2 steps)
HIV OneStepHIV ChemtronBio Lateralflow, Pointofcare,inc Wholeblood, 10minutes Indevelopment
test http://www.chemtron. immunochromatographictest clinics: plasmaorserum
bio.com Cost:inEurope0.60(approx) performedby
doctor,nurse,or
technician
HIV DualPath ChemBioDiagnostic Rapidchromatographiclateral Pointofcare Wholeblood, 20minutes Indevelopment
Platform SystemsInc flowimmunoassay. serum,plasma
Technology http://www.chembio.c oralfluid
(DPP)HIV12 om Companysaysthatthisdualpath
rapidtest platformsystemcanachieve
greatersensitivitythan
conventionalsinglepathlateral
flowassays
HIV OraQuick OraSureTechnologies Singleusequalitative Pointofcare, Oralfluid,plasma, 20minutes CEmarkedJune2007
ADVANCE Inc immunoassaytodetectantibodies e.g.outreach wholeblood andavailable,butnot
HIV1/2 http://www.orasure.co toHIV1/2.Manuallyperformed programmeand (fingerstickand widelyusedand
AntibodyTest m andvisuallyread mobiletesting venipuncture) researchisongoing6
clinics
Tradename:
'Advance
Awareness'
HIV OnSiteHIV1+ CTKBiotechInc Twolinelateralflowrapidtest Pointofcare Wholeblood, 20minutes NotyetCEmarked
2AbCombo http://www.ctkbiotech serumand butavailable
RapidTest .com plasma elsewhere
HIV LiatHIVAssay IQuumInc Viralloadtesttodetermine Pointofcare, 200lplasma. <1hour Indevelopment
http://www.iquum.co diseaseprognosisandmonitor e.g.emergency Theuseofwhole (marketresearch
m antiretroviraltherapy.Fully room,AIDS bloodiscurrently beingconducted)
automated,sensitiveandfast clinic.Useby under
quantitativeHIVassayfornear doctor,nurse development Studiesofclinical

6
PilotobservationalstudyofuseinUnitedStatesemergencydepartmentsstarted2007.Seehttp://clinicaltrials.gov/ct2/show/record/NCT00548041fordetails(last
updatedNovember2007)

8
 patientapplication.Isperformed technician utilityplanned
onIQuum'sLabinatube'(Liat)
system

HBV INSTIHepB(60 BioLyticalLaboratories Rapidinvitroqualitativeflow Pointofcare, Wholeblood 60seconds Indevelopment
sec)Surface http://www.biolytical.c throughtestforthedetectionof inc.antenatal (fingerstick),
AntigenRapid om antibodiestoHBV clinic.Canbe plasmaorserum
AntibodyTest performedbya
Cost:estimatedcostinEuropeUSD nurse/trained
$810pertest personnel
HBV CrystalHBsAg SpanDiagnostics Onestepflowthrough Pointofcare Plasmaorserum 15minutes
test(deviceor http://www.spandiag.c immunochromatographicvisual
dipstick) om qualitativetestforthedetectionof
HepatitisBSurfaceAntigen.
Availableinadeviceordipstick
format
HBV OnSiteHBsAb CTKBiotechInc Lateralflowchromatographic Pointofcare Plasmaand 15minutes Indevelopment
RapidTest http://www.ctkbiotech immunoassayforthequalitative serum
.com detectionofantibodiesincluding
IgG,IgMandIgAtoHepatitisB
SurfaceAntigen.Intendedfor
screeningpurposes
HBV SDBioline StandardDiagnostics Onestepimmunochromato Pointofcare Serumand 20minutes Availablebutnot
Hepatitistests Inc graphicassays plasma,and widelyusedintheUK
(HBsAg, http://www.standardia blood(onlyfor
AntiHBs, .com HBsAG)
HBeAg/HBsAg)
HBV OneStep ChemtronBio Lateralflow, Pointofcare,inc Wholeblood, 20minutes Indevelopment
HBsAgtest http://www.chemtron. immunochromatographictest clinics: plasmaand
bio.com Cost:inEurope0.32(approx) performedby serum
doctor,nurse,or
technician

Syphilis INSTISyphilis BioLyticalLaboratories Rapidinvitroqualitativeflow Pointofcare, Wholeblood 60seconds Indevelopment
(60sec)Rapid http://www.biolytical.c throughtestforthedetectionof inc.antenatal (fingerstick),
AntibodyTest om antibodiestoTreponemapallidum clinic.Canbe plasmaorserum

9
 performedbya
Cost:estimatedcostinEuropeUSD nurse/trained
$810pertest personnel
Syphilis SignalTP SpanDiagnostics Flowthrough Pointofcare Serumorplasma 10minutes CEmarkedrecently
device http://www.spandiag.c immunochromatographictestfor (2008)
om thequalitativedetectionof
antibodiestoTreponemapallidum
Syphilis SDBioline StandardDiagnostics Onestepqualitative Pointofcare Wholeblood, 520 CEmarkedbutnot
Syphilis3.0 Inc immunochromatographic plasmaand minutes widelyusedintheUK
http://www.standardia screeningassayforthedetection serum EvaluatedbyWHO
.com ofantibodiestoallisotopesagainst SDI:excellent
Treponemapallidum(IgG,IgMand performance
IgA).Lateralflowtest,cassette
mounted(extrasuppliedneeded)
Syphilis SyphCheck HealthcareProviders Immunochromatographiccolloidal Pointofcare 2dropsofwhole 1015 CEmarkedand
POC(also DirectInc goldantiIgG/IgA/IgMconjugate (clinicorGPs blood(finger minutes available,butnot
knownas http://www.healthcare andusingrecombinantcapture surgery). stick),or1drop widelyusedand
SyphPoc) providersdirect.com antigens. Company ofeitherserum, researchisongoing7
intendstoseek plasma
Benefits:companycommentsthat anFDACLIA
recombinantantigensmakethe waiverso
testhighlyspecific,anddetection untrained
ofIgGandIgMallowsfordetection personnelcan
ofallstagesofinfection. performthetest
Syphilis SyphicheckWB QualproDiagnostics ModifiedTPHAforthedetectionof Pointofcare Wholeblood, 15minutes CEmarkedrecently
http://www.tulipgroup TreponemaspecificIgGandIgM serumand (2008)
.com antibodies,selfperforming,double plasma
antigensandwichimmunoassay.
Cassettemountedlateralflow
device(noextrasuppliedneeded)
Syphilis ESPLINETP FujirebioDiagnostics Manualcassettemountedrapid Antenatalclinic. Serumorplasma 15minutes Availablebutnotyet

7
Thecompanyhasinformedusofaclinicalstudy(n=1,200)juststartedat3centres,thatisduetocompleteMay/June2009.Preliminaryresultson>200patientsamples
testedbyRPR,TPPA,TPHAandFTAyieldedacollectivesensitivityof97.6%andspecificityof98.3%versustreponemaltests.Searchingonlinetrialdatabasesfoundastudy
ofvalidity:sensitivityandspecificityinprogress(n=600),startedOct08,completingJune2009.Seehttp://clinicaltrials.gov/ct2/show/record/NCT00732355fordetails.This
maybethesamestudy.

10
 Syphilistest Inc membranelateralflowtest(extra Canbe widelyusedintheUK
http://www.fujirebio.c suppliesmaybeneeded) performedby
o.jp doctor/nurse/te
chnician
Syphilis OnSiteSyphilis CTKBiotechInc Lateralflowchromatographic Pointofcare Wholeblood, 15minutes CEmarkedandnew
AbCombo http://www.ctkbiotech immunoassayforthequalitative plasmaand
RapidTest .com detectionofantibodiesincluding serum
IgG,IgMandIgAforTreponema
pallidum.Intendedforscreening
purposes
Syphilis QuickView LumiQuick Immunochromatographiclateral Hospital,clinical 120150l(3 20minutes Indevelopment
Syphilis http://www.lumiquick. flowrapidtestdeviceforthe laboratory, drops)ofwhole
AntibodyTest com detectionofantibodiesto bloodstation blood,serumor
Treponemapallidum plasma
Syphilis SerodiaTP.PA FujirebioDiagnostics Rapidmanualqualitativegelatin Antenatalclinic. Serumand 2hours Availablebutnotyet
Syphilistest Inc particleagglutinationassayforthe Requiresa plasma widelyusedintheUK
http://www.fujirebio.c detectionofantibodiesto technicianto
o.jp Treponemapallidum performit
Syphilis Hexagon HumanDiagnostics Immunochromatographicrapid Pointofcare Wholeblood, 520 RecentlyCEmarked
Syphilis(3rd Worldwide(Human lateralflowtestforTreponema serumand minutes andavailable
generation) GmbH) pallidumIgG,IgM,IgAantibodies plasma
http://www.human.de
http://www.human
de.com

Rubella QuickView LumiQuick Immunochromatography,lateral Pointofcare, Wholeblood, 20minutes Indevelopment
RubellaIgG http://www.lumiquick. flowtest.Coplantocombinethe professionaluse plasmaand
test com QuickViewRubellaIgGandIgM serum Clinicaltrialsongoing
testsinonesingledevice
Rubella QuickView LumiQuick Immunochromatography,lateral Pointofcare, Wholeblood, 20minutes Indevelopment
RubellaIgM http://www.lumiquick. flowtest.Coplantocombine professionaluse plasmaand
test com QuickViewRubellaIgGandIgM serum Clinicaltrialsongoing
testsinonesingledevice

Combi INSTIHIV1/2& BioLyticalLaboratories Rapidinvitroqualitativeflow Pointofcare, Wholeblood(50 60seconds Indevelopment
HIV/ Syphilis(60 http://www.biolytical.c throughtestforthesimultaneous e.g.antenatal gcapillary),

11
Syphilis sec)Combo om detectionofantibodiestoHIV1/2 clinic.Canbe plasmaand
RapidTest andTreponemapallidum performed serum
nurse/trained
Cost:estimatedcostinEuropeUSD personnel
$1215pertest
Combi MultiPloRapid MedMiraLaboratories Flowthroughtechnology Pointofcareor Wholeblood, 3minutes Fullydeveloped;
HBV/HI HBV/HIV/HCV http://www.medmira.c nearpatient plasmaand availableinRussia
V/HCV AntibodyTest. om settings serum
Combi QuickProfile LumiQuick Immunochromatographiclateral Pointofcare, Wholeblood, 20minutes Indevelopment
HIV/HB BloodScreen http://www.lumiquick. flowthroughtest performedby plasmaand (evaluationphase).
sAg/Syp Panel com technicianor serum CEmarkingplans
hilis nurse undecided

12
Table3.BListtechnologies(maymeetthereviewcriteria,butinformationincomplete)

Disease Testname Company Descriptionandcost Settingforuse Sampletype Timeto CEmarking/
results availability
HIV RapidAntiHIV InTecProductsInc Colloidalgoldenhanced,rapid Pointofcare Wholeblood, 15minutes Detailsrequested
(1&2)Test http://www.intecasi.co immunochromatographicassayfor plasmaorserum
m thequalitativedetectionof
antibodiestoHIV.Intendedfor
screeningpurposes
HIV Advanced InTecProductsInc Colloidalgoldenhanced,rapid Pointofcare Urine 15minutes Detailsrequested
QualityRapid http://www.intecasi.co immunochromatographicassayfor
AntiHIV(1&2) m thequalitativedetectionof
Test antibodiestoHIV.Intendedfor
screeningpurposes
HIV BiorapidHIV BioLyticalLaboratories Immunochromatographic Details Wholeblood, 20minutes CEmarkedand
1&2 http://www.biolytical.c screeningtestforthedetectionof requested serum,plasma available
om antibodiestoHIVtype1/2
HIV AwareHIV1/2 CalypteBiomedical Singleuse qualitative,visually Pointofcare Oralfluid,plasma, 20minutes Detailsrequested
OMT Corporation readinvitroimmunoassayforthe use:doctors wholeblood
http://www.calypte.co detectionofantibodiestoHIV office,test (fingerstick+
m type1andtype2inoralfluid centres venipuncture)
specimens(oralmucosal
transudate).

HBV Hexagon HumanDiagnostics Immunochromatographic1step Pointofcare. Serumand 2030 NotyetCEmarked.
HBsAg1Step Worldwide(akaHuman lateralflowtestforHepatitisB Canbe plasma minutes
GmbH) surfaceantigen(HBsAg) performedbya
http://www.human.de doctor,nurseor
and technician
http://www.human
de.com
HBV MiraWellHBV MedMiraLaboratories Rapiddiagnostictestforthe Pointofcare, Wholeblood, 3minutes NotyetCEmarked.
RapidTest, http://www.medmira.c detectionofHepatitisBcore e.g.clinical plasmaorserum
PointofCare om antibody laboratories,
Format mobiletesting

13
 clinics

Syphilis AssureSyphilis MPBiomedicals Rapidchromatographicmembrane Pointofcare Serumorplasma 10minutes CEmarkedand
rapidtest (subsidiary=Genelabs basedimmunoassayforthe available
Diagnostics) qualitativedetectionofantibodies
http://www.mpbio.com (IgGandIgM)toTreponema
pallidum
Syphilis OneStep INDDiagnosticsInc Qualitativeimmunoassayfor Details Wholeblood, 1020 Available
SyphilisTest http://www.ind.ca detectingantibodiesspecificto requested serumorplasma minutes
Treponemapallidumantigens

Syphilis LIAISON DiaSorinSpA Fullyautomated Details Serumorplasma 40minutes Detailsrequested
Treponema http://www.diasorin.co chemiluminescentbasedtest requested
screen m


Rubella LIAISON DiaSorin Fullyautomatedquantitative Details Serumorplasma 35minutes FDAapprovedQ4
RubellaIgG http://www.diasorin.co chemiluminescenttestforthe requested 2008.
m determinationofIgG

Rubella LIAISON DiaSorin Fullyautomatedquantitative Details Serumorplasma 45minutes FDAapprovedQ4
RubellaIgM http://www.diasorin.co chemiluminescenttestforthe requested 2008.
m determinationofIgM

Rubella OnSiteRubella CTKBiotechInc Lateralflowchromatographic Pointofcare Detailsrequested Details Indevelopment.
RapidTest http://www.ctkbiotech. immunoassay,intendedfor requested
com screeningpurposes

14
Table4.Technologiesnotwithinremitbutthatmaybeofinterest

Disease Testname Company Description Setting Sample Timeto CE Comment
foruse type results marking/
availability
Syphilis Multiplextest Randox PCRbaseddetection Blood, 46 Indevelop
(combi indevelopment http://www.ra array.Singlemultiplex urine, hours ment
with thatincludes ndox.com biochip,runsontheir swab (enteringa
other Syphilis(also Multitstatplatform. validation
STDs) herpessimplex AutomatedDNA studies)
I/II,chlamydia extractionfollowedby CEexpected
trachomatis, singletubePCRandan within18
Neisseria automatedbiochipassay months
gonorrhoea,
Trichomonas
vaginalis)
HIV DetermineHIV InvernessMedical Available Expertsays:thisisthemostpopular
1/2Ag/Ab testintheUK,andquitewidelyusedin
Combotest outreachtestingvenues.A4th
generationiscomingoutthatshould
improvesensitivityatthetimeof
primaryinfection
Rubella Rapidrubella InvernessMedical Available
test

15
Discussion

APOCTisdefinedasananalyticaltestundertakenbyamemberofthehealthcareteamor
by a nonmedical individual in a setting distinct from a normal hospital laboratory (Royal
College of Pathologists, 2004). This term encompasses tests requiring varying degrees of
manual versus automated processing, but what we were looking for primarily were fully
automatedblackboxsystems,whichrequirejusttheadditionofthesampleandaresult
reading a specific time later. However, it was often unclear from company literature
whether tests were suitable for this kind of minimalhandling POC use, or what kind of
personnelwereintendedtoperformthem.Teststhatrunonplasmaorserumsampleswere
included,althoughtheyrequiresomeprocessingofwholeblood.

Achieving company engagement in the first instance proved problematic in several cases.
Eight of the 39 companies approached did not respond, despite repeated requests for
information. Of the 31 companies that did communicate with us, several requests were
neededtoobtainasmuchoftherequiredinformationaspossible.TheBListtechnologies
couldnotbeeliminatedortransferredtotheAListbecausekeyinformationcouldnotbe
obtained from the company. This was partly due to a lack of time, but not entirely. For
example, one question that many companies were unable to answer was whether an
existing test was widely used in the UK or not. Several tests remain on the BList for this
reason,andmoretimewouldnothavehelped.Instead,consultingaUKpathologyexpert/s
mightresolvethequestion.

Methodsused
Thisreportprovidesasummaryoftheintelligencegatheredduringthereview.Thereview
acted as a pilot and some useful methodological findings emerged from the process,
including:

Thecentralstrategydevelopedinthisreviewofidentifyingactivecompaniesandthen
engagingwiththemdirectlywaseffectiveandconsideredtoprovidethebestmeansof
obtaininggoodqualitycurrentintelligence.

The most useful information sources for the initial identification of active companies
wereonlineproductlistings.

ConsultingPOCTexpertswasvaluable.

Approachingtradeassociationsandprofessionalorganisationsforadvicedidnotprove
tobeveryuseful.

In vitro diagnostics is a fast moving field. Product lines are constantly evolving and
technical specifications and evaluative data therefore become rapidly out of date. For
this reason general internet searching (e.g. Google) should be concentrated on
informationthatislessthanoneyearold.

16
 Searchingtheclinicaltrialdatabaseswastimeconsumingandnotproductive:onlythree
technologieswerefound,andthesehadalreadybeenmorereadilyidentifiedfromother
sources.

Searching databases of published primary and tertiary research such as Medline and
Cochrane reviews was attempted, but the volume of information generated was too
greattoprocessproductivelyandtheinformationwasofteninsufficientlycurrent.

Thereviewwasconductedoversixweeks,bytheequivalentofonefulltimeNHSCHorizon
Scanner. The original deadline of four weeks was unrealistic in view of the extensive
company engagement involved, and was extended to six weeks. However, in view of the
time lags inherent in communications with companies, a longer timescale such as 36
monthswouldhavebeenmoreproductive.

Conclusion

ThirtyonenewandemergingrapidtestsforthepointofcarediagnosticscreeningofHIV,
HepatitisB,andorsyphilisinfectionand/orrubellasusceptibilitywereidentified,including
three combination tests. These may provide future options for national POC antenatal
screening for infectious diseases. Twelve further technologies that may also be relevant
wereidentified,butfurtherinformationfromthecompaniesisrequired.

17
Annexes

Annex1 Expertsandorganisationscontacted
Annex2 Onlinesources
Annex3 Searchterms

Annex1 Expertsandorganisationscontacted

Expertscontacted
ProfessorJohnParry,HealthProtectionAgency(HPA).Microbiologistwithexpertiseinthe
evaluationofrapidtestsforHIV
DrKeithPerry,DirectoroftheHPAMicrobiologicalDiagnosticAssessmentService(MiDAS)
DrLauravanDommelen.Expertonevaluatingrapidsyphilistests
DrTimWreghitt,VicePresidentoftheCollegeofPathologists,andavirologist
DrStephenGillespie,ChairofMicrobiologySAC,RoyalCollegeofPathologists
DrRosannaPeeling.HeadofWHO/TDRSTDDiagnosticsInitiative(SDI)
DrCathyIson,HPAexpertonsyphilistests

Professionalorganisationscontacted
MicrobiologicalDiagnosticAssessmentService,MiDAS(HealthProtectionAgency)
RoyalCollegeofPathologists,RCPath
InfectiousDiseaseResearchNetwork,IDRN
AssociationofClinicalBiochemists,ACB(consultedviatheironlinechatroombyDrPenny
Wilson)
EuropeanCentreforDiseasePreventionandControl,ECDC
InternationalFederationofClinicalChemistryandLaboratoryMedicine,IFCC
WorldAssociationofSocietiesofPathologyandLaboratoryMedicine,WASPaLM
AmericanAssociationofClinicalBiochemists,AACC

TradeAssociationscontacted
EuropeanDiagnosticManufacturersAssociation,EDMA
GermanIVDtradeassociation,VDGH
IrishMedicalDevicesAssociation,IMDA
IrishMedical&SurgicalTradeAssociation,IMSTA
NetherlandsIVDtradeassociation,Diagned

18
Annex2 Onlinesources

2.1 Diagnosticproductlistings

RDTInfo,http://www.http://www.rapiddiagnostics.org
PointofCare.net,http://www.pointofcare.net
WHOwebsite,http://www.who.int/std_diagnostics
LabTestsOnline,http://www.labtestsonline.org
Biokits,http://www.biokits.com/listDiagnostics

2.2 HorizonScanningandHealthTechnologyAssessmentorganisationtechnologydatabases

NHSCinhousetechnologydatabase
HTAProgramme,http://www.ncchta.org
InternationalNetworkAssociationforHealthTechnologyAssessment(INAHTA),
http://www.york.ac.uk
ECRI,http://www.ecri.org
Euroscan,http://www.euroscan.bham.ac.uk
CADTH,Canada,http://www.cadth.ca
AustraliaandNewZealandHorizonScanningNetwork(ANZHSN),http://www.horizon
scanning.gov.au
Medica,http://www.medica.de
IVDTechnology,http://www.devicelink.com

2.3 LicensingorganisationoutsideoftheEU

FDAOfficeofInVitroDiagnosticDeviceevaluationandsafety(OIVD),
http://www.fda.gov/CDRH/oivd

2.4 Clinicaltrialdatabases

WHOInternationalClinicalTrialsRegistry,http://www.who.int/trialsearch
CurrentControlledTrials,http://www.controlledtrials.com
ClinicalTrials.gov,http://www.clinicaltrials.gov
UKCRNPortfolioDatabase,http://www.public.ukcrn.org.uk/search

19
Annex3 Searchterms

Testterms Diseaseterms
Pointofcare HIV
Pointofcare Syphilis
POCT pallidum
POC Rubella
Rapidtest Germanmeasles
Rapid HepatitisB
Investigational HepB
Newtest HBV
New HBsAg

The test and disease terms were combined using and/or instructions to build up search
queries.

20
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