Systematic review and meta-analysis of the growth and rupture rates of small abdominal aortic

136 Pages·2013·3.58 MB·English

HEALTH TECHNOLOGY ASSESSMENT
VOLUME 17 ISSUE 41 SEPTEMBER 2013
ISSN 1366-5278
Systematic review and meta-analysis of the
growth and rupture rates of small abdominal
aortic aneurysms: implications for surveillance
intervals and their cost-effectiveness
SG Thompson, LC Brown, MJ Sweeting, MJ Bown, LG Kim,
MJ Glover, MJ Buxton, JT Powell and the RESCAN collaborators
DOI 10.3310/hta17410

Systematic review and meta-analysis of
the growth and rupture rates of small
abdominal aortic aneurysms:
implications for surveillance intervals
and their cost-effectiveness
SG Thompson,1,** LC Brown,2 MJ Sweeting,3 MJ Bown,4
LG Kim,5 MJ Glover,6 MJ Buxton,6 JT Powell7
†
and the RESCAN collaborators
1Department of Public Health and Primary Care, University of Cambridge,
Cambridge, UK
2Medical Research Council Clinical Trials Unit, London, UK
3Medical Research Council Biostatistics Unit, Cambridge, UK
4Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
5Department of Medical Statistics, London School of Hygiene and Tropical
Medicine, London, UK
6Health Economics Research Group, Brunel University, Uxbridge, UK
7Vascular Surgery Research Group, Imperial College London, London, UK
*Corresponding author
†RESCAN collaborators listed in Acknowledgements
Declared competing interests of authors: none
Published September 2013
DOI: 10.3310/hta17410
This report should be referenced as follows:
ThompsonSG,BrownLC,SweetingMJ,BownMJ,KimLG,GloverMJ,etal.Systematicreviewand
meta-analysisofthegrowthandruptureratesofsmallabdominalaorticaneurysms:implicationsfor
surveillance intervals and their cost-effectiveness. Health Technol Assess 2013;17(41).
Health Technology Assessment is indexed and abstracted in Index Medicus/MEDLINE, Excerpta
Medica/EMBASE, Science Citation Index Expanded (SciSearch®) and Current Contents®/
Clinical Medicine.

Health Technology Assessment HTA/HTATAR
ISSN1366-5278(Print)
ISSN2046-4924(Online)
Five-yearimpactfactor:5.804
HealthTechnologyAssessmentisindexedinMEDLINE,CINAHL,EMBASE,TheCochraneLibraryandtheISIScienceCitationIndexandis
assessedforinclusionintheDatabaseofAbstractsofReviewsofEffects.
ThisjournalisamemberofandsubscribestotheprinciplesoftheCommitteeonPublicationEthics(COPE)(www.publicationethics.org/).
Editorialcontact:[email protected]
ThefullHTAarchiveisfreelyavailabletoviewonlineatwww.journalslibrary.nihr.ac.uk/hta.Print-on-demandcopiescanbepurchasedfromthe
reportpagesoftheNIHRJournalsLibrarywebsite:www.journalslibrary.nihr.ac.uk
Criteriaforinclusion in theHealthTechnologyAssessmentjournal
ReportsarepublishedinHealthTechnologyAssessment(HTA)if(1)theyhaveresultedfromworkfortheHTAprogramme,and(2)they
areofasufficientlyhighscientificqualityasassessedbythereviewersandeditors.
ReviewsinHealthTechnologyAssessmentaretermed‘systematic’whentheaccountofthesearchappraisalandsynthesismethods(to
minimisebiasesandrandomerrors)would,intheory,permitthereplicationofthereviewbyothers.
HTA programme
TheHTAprogramme,partoftheNationalInstituteforHealthResearch(NIHR),wassetupin1993.Itproduceshigh-qualityresearch
informationontheeffectiveness,costsandbroaderimpactofhealthtechnologiesforthosewhouse,manageandprovidecareintheNHS.
‘Healthtechnologies’arebroadlydefinedasallinterventionsusedtopromotehealth,preventandtreatdisease,andimproverehabilitation
andlong-termcare.
ThejournalisindexedinNHSEvidenceviaitsabstractsincludedinMEDLINEanditsTechnologyAssessmentReportsinformNationalInstitute
forHealthandCareExcellence(NICE)guidance.HTAresearchisalsoanimportantsourceofevidenceforNationalScreeningCommittee(NSC)
policydecisions.
FormoreinformationabouttheHTAprogrammepleasevisitthewebsite:www.hta.ac.uk/
This report
TheresearchreportedinthisissueofthejournalwasfundedbytheHTAprogrammeasprojectnumber08/30/02.Thecontractualstartdatewas
inNovember2009.ThedraftreportbeganeditorialreviewinJuly2012andwasacceptedforpublicationinNovember2012.Theauthorshave
beenwhollyresponsibleforalldatacollection,analysisandinterpretation,andforwritinguptheirwork.TheHTAeditorsandpublisherhavetried
toensuretheaccuracyoftheauthors'reportandwouldliketothankthereviewersfortheirconstructivecommentsonthedraftdocument.
However,theydonotacceptliabilityfordamagesorlossesarisingfrommaterialpublishedinthisreport.
ThisreportpresentsindependentresearchfundedbytheNationalInstituteforHealthResearch(NIHR).Theviewsandopinionsexpressedby
authorsinthispublicationarethoseoftheauthorsanddonotnecessarilyreflectthoseoftheNHS,theNIHR,NETSCC,theHTAprogrammeor
theDepartmentofHealth.Ifthereareverbatimquotationsincludedinthispublicationtheviewsandopinionsexpressedbytheinterviewees
arethoseoftheintervieweesanddonotnecessarilyreflectthoseoftheauthors,thoseoftheNHS,theNIHR,NETSCC,theHTAprogrammeor
theDepartmentofHealth.
©Queen'sPrinterandControllerofHMSO2013.ThisworkwasproducedbyThompsonetal.underthetermsofacommissioning
contractissuedbytheSecretaryofStateforHealth.Thisissuemaybefreelyreproducedforthepurposesofprivateresearchand
studyandextracts(orindeed,thefullreport)maybeincludedinprofessionaljournalsprovidedthatsuitableacknowledgementis
madeandthereproductionisnotassociatedwithanyformofadvertising.Applicationsforcommercialreproductionshouldbe
addressedto:NIHRJournalsLibrary,NationalInstituteforHealthResearch,Evaluation,TrialsandStudiesCoordinatingCentre,
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 Health Sciences, 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
Dr Tom Marshall Reader in Primary Care, School of Health and Population Sciences, University of Birmingham, 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 Honorary Professor, Business School, Winchester University and Medical School,
University of Warwick, UK
Professor Jane Norman Professor of Maternal and Fetal Health, University of Edinburgh, UK
Professor John Powell Consultant Clinical Adviser, 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 Professorial Research Associate, University College London, 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/hta17410 HEALTHTECHNOLOGYASSESSMENT2013 VOL. 17 NO.41
Abstract
Systematic review and meta-analysis of the growth
and rupture rates of small abdominal aortic aneurysms:
implications for surveillance intervals and their
cost-effectiveness
SG Thompson,1* LC Brown,2 MJ Sweeting,3 MJ Bown,4 LG Kim,5
MJ Glover,6 MJ Buxton,6 JT Powell7 and the RESCAN collaborators†
1Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
2Medical Research Council Clinical Trials Unit, London, UK
3Medical Research Council Biostatistics Unit, Cambridge, UK
4Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
5Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK
6Health Economics Research Group, Brunel University, Uxbridge, UK
7Vascular Surgery Research Group, Imperial College London, London, UK
*Corresponding author
†RESCAN collaborators listed in Acknowledgements
Background: Small abdominal aortic aneurysms (AAAs; 3.0–5.4cm in diameter) are usually asymptomatic
andmanagedbyregularultrasoundsurveillanceuntiltheygrowtoadiameterthreshold(commonly5.5cm)
at which surgical intervention is considered. The choice of appropriate surveillance intervals is governed
by the growth and rupture rates of small AAAs, as well as their relative cost-effectiveness.
Objectives: The aim of this series of studies was to inform the evidence base for small AAA surveillance
strategies. This was achieved by literature review, collation and analysis of individual patient data, a focus
group and health economic modelling.
Datasources:WeundertooksystematicliteraturereviewsofgrowthratesandruptureratesofsmallAAAs.
The databases MEDLINE, EMBASE on OvidSP, Cochrane Central Register of Controlled Trials 2009 Issue 4,
ClinicalTrials.gov, and controlled-trials.com were searched from inception up until the end of 2009. We
also obtained individual data on 15,475 patients from 18 surveillance studies.
Review methods: Systematic reviews of publications identified 15 studies providing small AAA growth
rates, and 14 studies with small AAA rupture rates, up to December 2009 (later updated to September
2012). We developed statistical methods to analyse individual surveillance data, including the effects of
patient characteristics, to inform the choice of surveillance intervals and provide inputs for health economic
modelling. We updated an existing health economic model of AAA screening to address the
cost-effectiveness of different surveillance intervals.
Results: In the literature reviews, the mean growth rate was 2.3mm/year and the reported rupture rates
varied between 0 and 1.6 ruptures per 100 person-years. Growth rates increased markedly with aneurysm
diameter,butinsufficientdetailwasavailabletoguidesurveillanceintervals.Basedonindividualsurveillance
data, for each 0.5-cm increase in AAA diameter, growth rates increased by about 0.5mm/year and
rupture rates doubled. To control the risk of exceeding 5.5cm to below 10% in men, on average a 7-year
surveillance interval is sufficient for a 3.0-cm aneurysm, whereas an 8-month interval is necessary for a
©Queen'sPrinterandControllerofHMSO2013.ThisworkwasproducedbyThompsonetal.underthetermsofacommissioningcontractissuedbytheSecretaryofStatefor
Health.Thisissuemaybefreelyreproducedforthepurposesofprivateresearchandstudyandextracts(orindeed,thefullreport)maybeincludedinprofessionaljournals v
providedthatsuitableacknowledgementismadeandthereproductionisnotassociatedwithanyformofadvertising.Applicationsforcommercialreproductionshouldbeaddressed
to:NIHRJournalsLibrary,NationalInstituteforHealthResearch,Evaluation,TrialsandStudiesCoordinatingCentre,AlphaHouse,UniversityofSouthamptonSciencePark,
SouthamptonSO167NS,UK.
ABSTRACT
5.0-cm aneurysm. To control the risk of rupture to below 1%, the corresponding estimated surveillance
intervals are 9 years and 17 months. Average growth rates were higher in smokers (by 0.35mm/year) and
lowerinpatientswithdiabetes(by0.51mm/year).Rupturerateswerealmostfourfoldhigherinwomenthan
men, doubled in current smokers and increased with higher blood pressure. Increasing the surveillance
interval from 1 to 2 years for the smallest aneurysms (3.0–4.4cm) decreased costs and led to a positive net
benefit. For the larger aneurysms (4.5–5.4cm), increasing surveillance intervals from 3 to 6 months led to
equivalent cost-effectiveness.
Limitations: There were no clear reasons why the growth rates varied substantially between studies.
Uniform diagnostic criteria for rupture were not available. The long-term cost-effectiveness results may be
susceptible to the modelling assumptions made.
Conclusions:SurveillanceintervalsofseveralyearsareclinicallyacceptableformenwithAAAsintherange
3.0–4.0cm. Intervals of around 1 year are suitable for 4.0–4.9-cm AAAs, whereas intervals of 6 months
would be acceptable for 5.0–5.4-cm AAAs. These intervals are longer than those currently employed in the
UK AAA screening programmes. Lengthening surveillance intervals for the smallest aneurysms was also
shown to be cost-effective. Future work should focus on optimising surveillance intervals for women,
studying whether or not the threshold for surgery should depend on patient characteristics, evaluating the
usefulness of surveillance for those with aortic diameters of 2.5–2.9cm, and developing interventions that
may reduce the growth or rupture rates of small AAAs.
Funding: The National Institute for Health Research Health Technology Assessment programme.
vi
NIHRJournalsLibrary www.journalslibrary.nihr.ac.uk
DOI:10.3310/hta17410 HEALTHTECHNOLOGYASSESSMENT2013 VOL. 17 NO.41
Contents
. . . . . . . . . . . . . .List of abbreviations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix
Scientific summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi
Chapter 1 Background 1
Abdominal aortic aneurysm screening 1
Surveillance for small abdominal aortic aneurysms 1
Growth rates of small abdominal aortic aneurysms 2
Rupture rates of small abdominal aortic aneurysms 3
Need for systematic review and individual patient data analysis 3
Costs and cost-effectiveness 3
Overall aim of the project 3
Chapter 2 Research objectives 5
Aims and objectives 5
Structure of the report 5
Chapter 3 Methods for systematic reviews of growth and rupture rates 7
Systematic literature review of small abdominal aortic aneurysm growth rates 7
Systematic literature review of small abdominal aortic aneurysm rupture rates 8
Chapter 4 Results of systematic reviews of growth and rupture rates 11
Systematic review and meta-analysis of small abdominal aortic aneurysm growth rates 11
Systematic review and meta-analysis of small abdominal aortic aneurysm rupture rates 17
Chapter 5 Methods for individual patient data analysis of existing
surveillance data 29
Data collection 29
Focus group 30
Statistical methods 31
Chapter 6 Results of individual patient data analysis of existing
surveillance data 33
Study characteristics 33
Small abdominal aortic aneurysm growth rates in men 33
Small abdominal aortic aneurysm rupture rates in men 39
Small abdominal aortic aneurysm growth and rupture rates in women 40
Predictors of small abdominal aortic aneurysm growth rates 44
Predictors of small abdominal aortic aneurysm rupture rates 46
Inputs to health economic modelling 48
Chapter 7 Methods for cost-effectiveness analysis of alternative
surveillance policies 51
Introduction 51
The initial model 52
Validation and recalibration of the previously published model to better reflect the 10-year
follow-up data from the Multi-centre Aneurysm Screening Study 52
©Queen'sPrinterandControllerofHMSO2013.ThisworkwasproducedbyThompsonetal.underthetermsofacommissioningcontractissuedbytheSecretaryofStatefor
Health.Thisissuemaybefreelyreproducedforthepurposesofprivateresearchandstudyandextracts(orindeed,thefullreport)maybeincludedinprofessionaljournals vii
providedthatsuitableacknowledgementismadeandthereproductionisnotassociatedwithanyformofadvertising.Applicationsforcommercialreproductionshouldbeaddressed
to:NIHRJournalsLibrary,NationalInstituteforHealthResearch,Evaluation,TrialsandStudiesCoordinatingCentre,AlphaHouse,UniversityofSouthamptonSciencePark,
SouthamptonSO167NS,UK.
CONTENTS
Adapting the model structure to fully incorporate unobserved ‘tunnel’ states 54
Re-estimation of current unit costs for screening interventions, and elective and
emergency surgery 59
Incorporating data from the NHS Abdominal Aortic Aneurysm Screening Programme 63
Incorporating size-specific growth and rupture rates from the RESCAN analyses 63
Analysis of cost-effectiveness using the adapted and updated model 65
Chapter 8 Results of cost-effectiveness analysis of alternative
surveillance policies 67
Alternative surveillance strategies 67
Uncertainty and sensitivity 69
Discussion and conclusions 69
Chapter 9 Discussion 73
Systematic review of small abdominal aortic aneurysm growth rates 73
Systematic review of small abdominal aortic aneurysm rupture rates 74
Analysis of individual patient data surveillance data sets 75
Factors influencing growth and rupture rates 76
Chapter 10 Conclusions 79
Clinical and policy conclusions 79
Research implications 80
Acknowledgements 83
References 87
Appendix 1 Protocol, search strategy and list of excluded studies for
systematic review of growth of small abdominal aortic aneurysms 95
Appendix 2 Protocol, search strategy and list of excluded studies for
systematic review of rupture of small abdominal aortic aneurysms 105
Appendix 3 Statistical methods and excluded studies for individual patient
data meta-analysis 113
Appendix 4 Statistical methods for cost-effectiveness analysis 117
viii
NIHRJournalsLibrary www.journalslibrary.nihr.ac.uk