The future for diagnostic tests of acute kidney injury in critical care

308 Pages·2017·2.6 MB·English

HEALTH TECHNOLOGY ASSESSMENT
VOLUME 22 ISSUE 32 MAY 2018
ISSN 1366-5278
The future for diagnostic tests of acute kidney injury
in critical care: evidence synthesis, care pathway
analysis and research prioritisation
Peter S Hall, Elizabeth D Mitchell, Alison F Smith, David A Cairns,
Michael Messenger, Michelle Hutchinson, Judy Wright, Karen Vinall-Collier,
Claire Corps, Patrick Hamilton, David Meads and Andrew Lewington
DOI 10.3310/hta22320

The future for diagnostic tests of acute
kidney injury in critical care: evidence
synthesis, care pathway analysis and
research prioritisation
Peter S Hall,1* Elizabeth D Mitchell,2
Alison F Smith,2,3 David A Cairns,4
Michael Messenger,3 Michelle Hutchinson,4
Judy Wright,2 Karen Vinall-Collier,2 Claire Corps,5
Patrick Hamilton,6 David Meads2 and
Andrew Lewington5
1Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, UK
2Academy of Primary Care, Hull York Medical School, Hull, UK
3National Institute for Health Research (NIHR) Diagnostic Evidence Co-operative
Leeds, Leeds, UK
4Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK
5Leeds Teaching Hospitals NHS Trust, Leeds, UK
6Manchester Institute of Nephrology and Transplantation, Central Manchester
University Hospitals NHS Foundation Trust, Manchester, UK
*Corresponding author
Declared competing interests of authors: Andrew Lewington hasreceived honoraria from Alere, Inc.
David Meads isamember of theHealth Technology Assessment programme Emergency and Hospital Care
panel. Patrick Hamilton hasreceived funding from ChemoCentryx, Inc., outside thiswork.
Published May 2018
DOI: 10.3310/hta22320
This reportshould be referenced as follows:
Hall PS,MitchellED,SmithAF,CairnsDA,MessengerM,HutchinsonM,etal.Thefuturefor
diagnostictestsofacutekidneyinjuryincriticalcare:evidencesynthesis,carepathwayanalysisand
researchprioritisation.HealthTechnolAssess2018;22(32).
HealthTechnology Assessment isindexed and abstracted in IndexMedicus/MEDLINE, Excerpta
Medica/EMBASE, ScienceCitation Index Expanded (SciSearch®) andCurrent Contents®/
Clinical Medicine.

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DOI:10.3310/hta22320 HEALTHTECHNOLOGYASSESSMENT2018 VOL.22 NO.32
Abstract
The future for diagnostic tests of acute kidney injury in
critical care: evidence synthesis, care pathway analysis
and research prioritisation
Peter S Hall,1* Elizabeth D Mitchell,2 Alison F Smith,2,3 David A Cairns,4
Michael Messenger,3 Michelle Hutchinson,4 Judy Wright,2
Karen Vinall-Collier,2 Claire Corps,5 Patrick Hamilton,6 David Meads2
and Andrew Lewington5
1Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, UK
2Academy ofPrimary Care, Hull YorkMedical School, Hull, UK
3National Institute for HealthResearch (NIHR) Diagnostic Evidence Co-operative Leeds, Leeds, UK
4Leeds Institute ofClinical Trials Research, University ofLeeds, Leeds, UK
5Leeds TeachingHospitals NHS Trust,Leeds, UK
6Manchester Institute ofNephrology and Transplantation, Central ManchesterUniversity
Hospitals NHS FoundationTrust, Manchester, UK
*Corresponding author [email protected]
Background: Acute kidney injury (AKI) is highly prevalent in hospital inpatient populations, leading to
significant mortality and morbidity, reduced quality of life and high short- andlong-term health-care costs
for the NHS. New diagnostictests may offer an earlier diagnosis or improved care, butevidence of benefit
to patients and of value to theNHS isrequired before national adoption.
Objectives: To evaluate thepotential for AKI invitro diagnostic tests to enhancethe NHS care of patients
admitted to the intensive careunit (ICU) and identify anefficient supporting research strategy.
Data sources:WesearchedClinicalTrials.gov,TheCochraneLibrarydatabases,Embase,HealthManagement
InformationConsortium,InternationalClinicalTrialsRegistryPlatform,MEDLINE,metaRegisterofCurrent
ControlledTrials,PubMedandWebofSciencedatabasesfromtheirinceptiondatesuntilSeptember2014
(review1),November2015(review2)andJuly2015(economicmodel).Detailsofdatabasesusedforeach
reviewandcoveragedatesarelistedinthemainreport.
Review methods: The AKI-Diagnostics project included horizon scanning, systematic reviewing,
meta-analysis of sensitivity and specificity, appraisal of analytical validity, carepathway analysis,
model-based lifetime economic evaluation from aUK NHS perspective and value of information
(VOI) analysis.
Results: Thehorizon-scanningsearchidentified152potentialtestsandbiomarkers.Threetests,Nephrocheck®
(AstuteMedical,Inc.,SanDiego,CA,USA),NGALandcystatinC,weresubjectedtodetailedreview.The
meta-analysiswaslimitedbyvariablereportingstandards,studyqualityandheterogeneity,butsensitivitywas
between0.54and0.92andspecificitywasbetween0.49and0.95dependingonthetest.Abespokecritical
appraisalframeworkdemonstratedthatanalyticalvaliditywasalsopoorlyreportedinmanyinstances.Inthe
economicmodeltheincrementalcost-effectivenessratiosrangedfrom£11,476to£19,324perquality-adjusted
life-year(QALY),withaprobabilityofcost-effectivenessbetween48%and54%whentestswerecompared
withcurrentstandardcare.
©Queen’sPrinterandControllerofHMSO2018.ThisworkwasproducedbyHalletal.underthetermsofacommissioningcontractissuedbytheSecretaryofStateforHealth
andSocialCare.Thisissuemaybefreelyreproducedforthepurposesofprivateresearchandstudyandextracts(orindeed,thefullreport)maybeincludedinprofessional v
journalsprovidedthatsuitableacknowledgementismadeandthereproductionisnotassociatedwithanyformofadvertising.Applicationsforcommercialreproductionshould
beaddressedto:NIHRJournalsLibrary,NationalInstituteforHealthResearch,Evaluation,TrialsandStudiesCoordinatingCentre,AlphaHouse,UniversityofSouthamptonScience
Park,SouthamptonSO167NS,UK.
ABSTRACT
Limitations: The major limitation in the evidence on tests was theheterogeneity between studies inthe
definitions of AKIand the timing of testing.
Conclusions: Diagnostic tests for AKIin the ICUoffer thepotential to improve patient care and add
value to theNHS, but cost-effectiveness remains highly uncertain. Further research should focus onthe
mechanisms by which anew test might change current careprocesses in the ICUand the subsequent cost
and QALY implications. TheVOI analysis suggested that further observational research to better define the
prevalence of AKI developingin theICU would beworthwhile. A formal randomised controlled trial of
biomarker use linked to astandardised AKIcare pathway is necessary to provide definitive evidence on
whether or not adoption of tests bythe NHS would beof value.
Study registration: The systematic review within thisstudy is registered as PROSPERO CRD42014013919.
Funding: TheNational Institute for Health Research HealthTechnology Assessment programme.
vi
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DOI:10.3310/hta22320 HEALTHTECHNOLOGYASSESSMENT2018 VOL.22 NO.32
Contents
List oftables xi
List offigures xv
List ofboxes xix
List ofabbreviations xxi
PlainEnglish summary xxiii
Scientific summary xxv
Chapter 1Background and introduction 1
Introduction 1
Theclinical problem 1
Theneed for research 1
Existing research 2
Adoptionof diagnostic tests in theNHS 3
TheNational Institute for Health Research Diagnostic Evidence Co-operatives 3
Technicalbackground for the methodological approach 3
Project objectives 4
Outlineof theproject components 5
Phase 1: systematic review 5
Phase 2: evidence synthesis and meta-analysis 5
Phase 3: care pathway analysis 5
Phase 4: decision-analytic model 5
Phase 5: sensitivity analysis andvalue of information analysis 5
Patient and public engagement in the study 6
Chapter 2Systematic review 7
Aim 7
Search 1: horizon scanning 7
Objective 7
Identification of studies 7
Selection of studies 8
Literature yield 8
Identification of candidate biomarkers 9
Search 2: identification of evidence for candidate tests 10
Objective 10
Identification of studies 10
Selection of studies 11
Data extraction 11
Quality assessment 12
Results of thesystematic review 12
Location and setting 14
Population 14
Biomarkers and outcome areas 16
©Queen’sPrinterandControllerofHMSO2018.ThisworkwasproducedbyHalletal.underthetermsofacommissioningcontractissuedbytheSecretaryofStateforHealth
andSocialCare.Thisissuemaybefreelyreproducedforthepurposesofprivateresearchandstudyandextracts(orindeed,thefullreport)maybeincludedinprofessional vii
journalsprovidedthatsuitableacknowledgementismadeandthereproductionisnotassociatedwithanyformofadvertising.Applicationsforcommercialreproductionshould
beaddressedto:NIHRJournalsLibrary,NationalInstituteforHealthResearch,Evaluation,TrialsandStudiesCoordinatingCentre,AlphaHouse,UniversityofSouthamptonScience
Park,SouthamptonSO167NS,UK.
CONTENTS
Quality assessment 16
Risk of bias amongstudies included in the evidence synthesis 17
Discussion 19
Chapter 3Meta-analysis of diagnostic tests for acutekidney injury 21
Introduction 21
Methods 21
Primary objective 21
Identification of studies 21
Study methods 21
Outcome measurements 21
Diagnostic and staging systems for acutekidney injury 22
Key data extracted 23
Study exclusion 23
Data analysis 23
Results 25
Nephrocheck 25
Neutrophil gelatinase-associated lipocalin 28
Cystatin C 42
Limitations 54
Summary 57
Chapter 4Measurement performance: aframework for the Quality Assessment
ofMeasurement Procedures using in vitro diagnostic medical devices in clinical
research 59
Introduction 59
Development of aframework for the Quality Assessment of Measurement Procedures 61
Testingthe Quality Assessment of Measurement Proceduresframework using
Nephrocheck as acasestudy 62
Discussion 65
Chapter 5Economic evaluation 71
Introduction 71
Overview of theeconomic evaluation 71
Methods 71
Population andperspective 71
Testing strategies 72
Costs and health outcomes 72
Literature review of acute kidney injury economic models 72
Focus group 76
Model structure 77
Initial decision tree model 77
Main Markov model 77
Impact of thetests 80
Modelparameter literature review 81
Primary searches 81
Additional searches 83
Acute kidney injury registry data 109
Modelparameters 113
Hospital period parameters 113
Follow-up period parameters 117
Test parameters 118
Post-cardiac surgery subgroup population parameters 121
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