High-sensitivity troponin assays for the early rule-out or diagnosis of acute myocardial infarction in

262 Pages·2015·1.66 MB·English

by  Westwood M

HEALTH TECHNOLOGY ASSESSMENT
VOLUME 19 ISSUE 44 JUNE 2015
ISSN 1366-5278
High-sensitivity troponin assays for the early rule-out
or diagnosis of acute myocardial infarction in people
with acute chest pain: a systematic review and
cost-effectiveness analysis
Marie Westwood, Thea van Asselt, Bram Ramaekers, Penny Whiting,
Praveen Thokala, Manuela Joore, Nigel Armstrong, Janine Ross,
Johan Severens and Jos Kleijnen
DOI 10.3310/hta19440

High-sensitivity troponin assays for the
early rule-out or diagnosis of acute
myocardial infarction in people with acute
chest pain: a systematic review and
cost-effectiveness analysis
Marie Westwood,1* Thea van Asselt,2 Bram Ramaekers,2
Penny Whiting,1 Praveen Thokala,3 Manuela Joore,2
Nigel Armstrong,1 Janine Ross,1 Johan Severens4
and Jos Kleijnen5
1Kleijnen Systematic Reviews Ltd, York, UK
2Department of Clinical Epidemiology and Medical Technology Assessment,
Maastricht University Medical Centre, Maastricht, The Netherlands
3Health Economics and Decision Science Group, School of Health and Related
Research (ScHARR), University of Sheffield, Sheffield, UK
4Institute of Health Policy and Management, Erasmus University Rotterdam,
Rotterdam, The Netherlands
5School for Public Health and Primary Care (CAPHRI), Maastricht University,
Maastricht, The Netherlands
*Corresponding author
Declared competing interests of authors: none
Published June 2015
DOI: 10.3310/hta19440
This reportshould be referenced as follows:
Westwood M, van Asselt T, Ramaekers B, Whiting P, Thokala P, JooreM, et al. High-sensitivity
troponin assaysfor theearly rule-out or diagnosis of acute myocardial infarction in people
withacute chest pain: asystematic reviewand cost-effectiveness analysis.Health Technol Assess
2015;19(44).
HealthTechnology Assessment isindexed and abstracted in IndexMedicus/MEDLINE, Excerpta
Medica/EMBASE, ScienceCitation Index Expanded (SciSearch®) andCurrent Contents®/
Clinical Medicine.

Health Technology Assessment NICETARandDAR
ISSN1366-5278(Print)
ISSN2046-4924(Online)
Impactfactor:5.116
HealthTechnologyAssessmentisindexedinMEDLINE,CINAHL,EMBASE,TheCochraneLibraryandtheISIScienceCitationIndex.
ThisjournalisamemberofandsubscribestotheprinciplesoftheCommitteeonPublicationEthics(COPE)(www.publicationethics.org/).
Editorialcontact:[email protected]
ThefullHTAarchiveisfreelyavailabletoviewonlineatwww.journalslibrary.nihr.ac.uk/hta.Print-on-demandcopiescanbepurchasedfromthe
reportpagesoftheNIHRJournalsLibrarywebsite:www.journalslibrary.nihr.ac.uk
CriteriaforinclusionintheHealthTechnologyAssessmentjournal
ReportsarepublishedinHealthTechnologyAssessment(HTA)if(1)theyhaveresultedfromworkfortheHTAprogramme,and(2)they
areofasufficientlyhighscientificqualityasassessedbythereviewersandeditors.
ReviewsinHealthTechnologyAssessmentaretermed‘systematic’whentheaccountofthesearchappraisalandsynthesismethods(to
minimisebiasesandrandomerrors)would,intheory,permitthereplicationofthereviewbyothers.
HTAprogramme
TheHTAprogramme,partoftheNationalInstituteforHealthResearch(NIHR),wassetupin1993.Itproduceshigh-qualityresearch
informationontheeffectiveness,costsandbroaderimpactofhealthtechnologiesforthosewhouse,manageandprovidecareintheNHS.
‘Healthtechnologies’arebroadlydefinedasallinterventionsusedtopromotehealth,preventandtreatdisease,andimproverehabilitation
andlong-termcare.
ThejournalisindexedinNHSEvidenceviaitsabstractsincludedinMEDLINEanditsTechnologyAssessmentReportsinformNationalInstitute
forHealthandCareExcellence(NICE)guidance.HTAresearchisalsoanimportantsourceofevidenceforNationalScreeningCommittee(NSC)
policydecisions.
FormoreinformationabouttheHTAprogrammepleasevisitthewebsite:http://www.nets.nihr.ac.uk/programmes/hta
Thisreport
TheresearchreportedinthisissueofthejournalwascommissionedandfundedbytheHTAprogrammeonbehalfofNICEasprojectnumber
13/51/01.TheprotocolwasagreedinSeptember2013.TheassessmentreportbeganeditorialreviewinApril2014andwasacceptedfor
publicationinOctober2014.Theauthorshavebeenwhollyresponsibleforalldatacollection,analysisandinterpretation,andforwritingup
theirwork.TheHTAeditorsandpublisherhavetriedtoensuretheaccuracyoftheauthors’reportandwouldliketothankthereviewersfor
theirconstructivecommentsonthedraftdocument.However,theydonotacceptliabilityfordamagesorlossesarisingfrommaterial
publishedinthisreport.
ThisreportpresentsindependentresearchfundedbytheNationalInstituteforHealthResearch(NIHR).Theviewsandopinionsexpressedby
authorsinthispublicationarethoseoftheauthorsanddonotnecessarilyreflectthoseoftheNHS,theNIHR,NETSCC,theHTAprogramme
ortheDepartmentofHealth.Ifthereareverbatimquotationsincludedinthispublicationtheviewsandopinionsexpressedbythe
intervieweesarethoseoftheintervieweesanddonotnecessarilyreflectthoseoftheauthors,thoseoftheNHS,theNIHR,NETSCC,theHTA
programmeortheDepartmentofHealth.
©Queen’sPrinterandControllerofHMSO2015.ThisworkwasproducedbyWestwoodetal.underthetermsofa
commissioningcontractissuedbytheSecretaryofStateforHealth.Thisissuemaybefreelyreproducedforthepurposesof
privateresearchandstudyandextracts(orindeed,thefullreport)maybeincludedinprofessionaljournalsprovidedthat
suitableacknowledgementismadeandthereproductionisnotassociatedwithanyformofadvertising.Applicationsfor
commercialreproductionshouldbeaddressedto:NIHRJournalsLibrary,NationalInstituteforHealthResearch,Evaluation,Trials
andStudiesCoordinatingCentre,AlphaHouse,UniversityofSouthamptonSciencePark,SouthamptonSO167NS,UK.
PublishedbytheNIHRJournalsLibrary(www.journalslibrary.nihr.ac.uk),producedbyPrepressProjectsLtd,Perth,Scotland
(www.prepress-projects.co.uk).
Editor-in-Chief of Health Technology Assessment and NIHR
Journals Library
Professor Tom Walley Director, NIHR Evaluation, Trials and Studies and Director of the HTA Programme, UK
NIHR Journals Library Editors
Professor Ken Stein Chair of HTA Editorial Board and Professor of Public Health, University of Exeter Medical
School, UK
Professor Andree Le May Chair of NIHR Journals Library Editorial Group (EME, HS&DR, PGfAR, PHR journals)
Dr Martin Ashton-Key Consultant in Public Health Medicine/Consultant Advisor, NETSCC, UK
Professor Matthias Beck Chair in Public Sector Management and Subject Leader (Management Group),
Queen’s University Management School, Queen’s University Belfast, UK
Professor Aileen Clarke Professor of Public Health and Health Services Research, Warwick Medical School,
University of Warwick, UK
Dr Tessa Crilly Director, Crystal Blue Consulting Ltd, UK
Dr Peter Davidson Director of NETSCC, HTA, UK
Ms Tara Lamont Scientific Advisor, NETSCC, UK
Professor Elaine McColl Director, Newcastle Clinical Trials Unit, Institute of Health and Society,
Newcastle University, UK
Professor William McGuire Professor of Child Health, Hull York Medical School, University of York, UK
Professor Geoffrey Meads Professor of Health Sciences Research, Faculty of Education, University of Winchester, UK
Professor John Powell Consultant Clinical Adviser, National Institute for Health and Care Excellence (NICE), UK
Professor James Raftery Professor of Health Technology Assessment, Wessex Institute, Faculty of Medicine,
University of Southampton, UK
Dr Rob Riemsma Reviews Manager, Kleijnen Systematic Reviews Ltd, UK
Professor Helen Roberts Professor of Child Health Research, UCL Institute of Child Health, UK
Professor Helen Snooks Professor of Health Services Research, Institute of Life Science, College of Medicine,
Swansea University, UK
Please visit the website for a list of members of the NIHR Journals Library Board:
www.journalslibrary.nihr.ac.uk/about/editors
Editorial contact: [email protected]
NIHRJournalsLibrary www.journalslibrary.nihr.ac.uk
DOI:10.3310/hta19440 HEALTHTECHNOLOGYASSESSMENT2015 VOL.19 NO.44
Abstract
High-sensitivity troponin assays for the early rule-out
or diagnosis of acute myocardial infarction in people
with acute chest pain: a systematic review and
cost-effectiveness analysis
Marie Westwood,1* Thea van Asselt,2 Bram Ramaekers,2
Penny Whiting,1 Praveen Thokala,3 Manuela Joore,2
Nigel Armstrong,1 Janine Ross,1 Johan Severens4 and Jos Kleijnen5
1Kleijnen Systematic Reviews Ltd, York, UK
2Department of Clinical Epidemiology andMedical Technology Assessment,
Maastricht University Medical Centre,Maastricht, The Netherlands
3Health Economics and Decision ScienceGroup, School of Healthand Related Research (ScHARR),
University ofSheffield, Sheffield, UK
4Institute of HealthPolicy and Management, Erasmus University Rotterdam, Rotterdam,
TheNetherlands
5School forPublic Healthand Primary Care(CAPHRI), Maastricht University, Maastricht,
TheNetherlands
*Corresponding author [email protected]
Background: Early diagnosis of acute myocardial infarction (AMI) can ensure quickand effective treatment
but only20% of adults with emergencyadmissions for chest painhave an AMI. High-sensitivity cardiac
troponin (hs-cTn) assaysmay allow rapid rule-out of AMI and avoidance of unnecessary hospital admissions
and anxiety.
Objective: To assess theclinical effectiveness and cost-effectiveness of hs-cTn assaysfor the early (within
4hours of presentation) rule-out of AMI in adults with acute chest pain.
Methods: Sixteen databases, including MEDLINE and EMBASE, research registers and conference
proceedings, were searched to October2013. Study quality was assessed usingQUADAS-2. Thebivariate
model was used to estimate summary sensitivity and specificity for meta-analyses involving fouror more
studies, otherwise random-effects logistic regression was used. Thehealth-economic analysis considered
the long-term costs and quality-adjusted life-years (QALYs) associated with different troponin (Tn) testing
methods. The denovo modelconsisted of a decision tree and Markov model. Alifetime time horizon
(60 years) was used.
Results: Eighteen studies were included in the clinical effectiveness review. The optimum strategy, based
on theRoche assay, used alimit of blank (LoB) threshold in apresentation sample to rule out AMI
[negative likelihood ratio (LR–)0.10, 95% confidence interval (CI)0.05 to 0.18]. Patients testing positive
could then have afurther test at 2hours; aresult abovethe99th centile on either sample and adelta (Δ)
of≥20% hassome potential for ruling in anAMI [positive likelihood ratio(LR+) 8.42, 95% CI 6.11 to
11.60], whereas aresult belowthe 99th centile onboth samples and a Δof <20% can beused to rule
out anAMI (LR–0.04, 95% CI 0.02 to 0.10). The optimum strategy, based on theAbbott assay, used a
limit of detection (LoD) threshold in apresentation sample to rule out AMI (LR– 0.01,95% CI 0.00 to
0.08). Patients testing positive could then have afurther test at 3hours; aresult abovethe 99th centile on
©Queen’sPrinterandControllerofHMSO2015.ThisworkwasproducedbyWestwoodetal.underthetermsofacommissioningcontractissuedbytheSecretaryofStatefor
Health.Thisissuemaybefreelyreproducedforthepurposesofprivateresearchandstudyandextracts(orindeed,thefullreport)maybeincludedinprofessionaljournals v
providedthatsuitableacknowledgementismadeandthereproductionisnotassociatedwithanyformofadvertising.Applicationsforcommercialreproductionshouldbe
addressedto:NIHRJournalsLibrary,NationalInstituteforHealthResearch,Evaluation,TrialsandStudiesCoordinatingCentre,AlphaHouse,UniversityofSouthamptonScience
Park,SouthamptonSO167NS,UK.
ABSTRACT
this sample hassome potential for ruling inan AMI (LR+10.16, 95% CI 8.38 to 12.31), whereas aresult
below the99th centile can beused to rule out an AMI (LR–0.02, 95% CI 0.01 to 0.05). In the base-case
analysis, standard Tn testing was both most effective and most costly. Strategies considered cost-effective
depending upon incremental cost-effectiveness ratio thresholds were Abbott 99th centile (thresholds
of <£6597), Beckman 99th centile (thresholds between £6597 and£30,042), Abbott optimal strategy
(LoD threshold at presentation, followed by99th centile threshold at 3hours) (thresholds between
£30,042 and £103,194) and the standard Tntest (thresholds over £103,194). TheRoche 99th centile and
the Rocheoptimal strategy [LoB threshold at presentation followed by99th centile threshold and/or Δ20%
(compared with presentation test) at 1–3 hours] were extendedly dominated in this analysis.
Conclusions: There is someevidence to suggest that hs-CTn testing may provide aneffective and
cost-effective approach to early rule-out of AMI. Further research is neededto clarify optimal diagnostic
thresholds and testing strategies.
Study registration: This study isregistered as PROSPERO CRD42013005939.
Funding: TheNational Institute for Health Research HealthTechnology Assessment programme.
vi
NIHRJournalsLibrary www.journalslibrary.nihr.ac.uk
DOI:10.3310/hta19440 HEALTHTECHNOLOGYASSESSMENT2015 VOL.19 NO.44
Contents
List oftables xi
List offigures xiii
Glossary xv
List ofabbreviations xvii
PlainEnglish summary xix
Scientific summary xxi
Chapter 1Objective 1
Chapter 2Background and definition ofthe decision problem(s) 3
Population 3
Intervention technologies 4
Abbott ARCHITECT high-sensitivity troponin I assay 4
AccuTnI+3 troponin Iassay (Beckman Coulter) 4
Roche Elecsys high-sensitivity troponin Tassay 5
Comparator 6
Carepathway 6
Diagnostic assessment 6
Management/treatment 7
Chapter 3Assessment of clinical effectiveness 9
Systematic review methods 9
Search strategy 9
Inclusion andexclusion criteria 10
Inclusion screening and dataextraction 10
Quality assessment 11
Methods of analysis/synthesis 11
Results of the assessment of clinical effectiveness assessment 12
Overview of included studies 13
Study quality 14
Diagnostic accuracy of theRoche Elecsys high-sensitivity cardiac troponin Tassay 16
Diagnostic accuracy of theAbbott ARCHITECT high-sensitivity cardiac troponin Iassay 26
DiagnosticaccuracyoftheBeckmanCoulterAccesshigh-sensitivitycardiactroponinIassay 30
ComparativediagnosticaccuracyoftheRocheElecsyshigh-sensitivitytroponinTassay,
theAbbottARCHITECThigh-sensitivitytroponinIassayandtheBeckmanCoulter
Accesshigh-sensitivitytroponinIassay 30
Selection of diagnostic strategies for inclusion in cost-effectiveness modelling 30
©Queen’sPrinterandControllerofHMSO2015.ThisworkwasproducedbyWestwoodetal.underthetermsofacommissioningcontractissuedbytheSecretaryofStatefor
Health.Thisissuemaybefreelyreproducedforthepurposesofprivateresearchandstudyandextracts(orindeed,thefullreport)maybeincludedinprofessionaljournals vii
providedthatsuitableacknowledgementismadeandthereproductionisnotassociatedwithanyformofadvertising.Applicationsforcommercialreproductionshouldbe
addressedto:NIHRJournalsLibrary,NationalInstituteforHealthResearch,Evaluation,TrialsandStudiesCoordinatingCentre,AlphaHouse,UniversityofSouthamptonScience
Park,SouthamptonSO167NS,UK.
CONTENTS
Chapter 4Assessment of cost-effectiveness 33
Review of economic analysesof high-sensitivity cardiac troponin assays 33
Search strategy 33
Inclusion criteria 33
Quality assessment 33
Results 33
Modelstructure and methodology 45
Troponin tests considered in the model 45
Model structure 47
Model parameters 48
Overview of main modelassumptions 53
Modelanalyses 54
Secondary analysis 54
Sensitivity analysis 54
Subgroup analysis 55
Results of cost-effectiveness analyses 56
Base-case analysis 56
Secondary analysis 59
Sensitivity analysis 62
Subgroup analysis 63
Chapter 5Discussion 65
Statement of principal findings 65
Clinical effectiveness 65
Cost-effectiveness 66
Strengths and limitations of assessment 68
Clinical effectiveness 68
Cost-effectiveness 70
Uncertainties 71
Clinical effectiveness 71
Cost-effectiveness 73
Chapter 6Conclusions 75
Implications for service provision 75
Suggested research priorities 75
Acknowledgements 77
References 79
Appendix 1Literature search strategies 105
Appendix 2Data extraction tables 121
Appendix 3QUADAS-2 assessments 143
Appendix 4Table ofexcluded studies with rationale 167
Appendix 5Sensitivity analyses (base case) 175
Appendix 6Sensitivity analyses (secondaryanalysis) 195
Appendix 7Subgroup analyses(base case) 215
viii
NIHRJournalsLibrary www.journalslibrary.nihr.ac.uk