Antiviral drugs for the treatment of influenza: a systematic review and economic evaluation

306 Pages·2009·3.25 MB·English

by  Burch J

Health Technology Assessment 2009; Vol. 13: No. 58
Antiviral drugs for the treatment of
influenza: a systematic review and
economic evaluation
J Burch, M Paulden, S Conti, C Stock,
M Corbett, NJ Welton, AE Ades,
A Sutton, N Cooper, AJ Elliot,
K Nicholson, S Duffy, C McKenna,
L Stewart, M Westwood, S Palmer
November 2009
DOI: 10.3310/hta13580
Health Technology Assessment
NIHR HTA programme
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AbstractR e...f.e..r.e..n..c..e..s. .............................................................................................i.i.i........147
List of abAbprpeveinadtiioxn 1s ........................................... vii
Antiviral drugs for the treatment of
Literature search strategies ........................157
Executive summary ............................................ ix
influenza: a systematic review and
Appendix 2
Chapter 1 Details of included studies ..........................173
economic evaluation
Background ................................................. 1
DescArippptieonnd.oixf. h3 ealth.problem..................... 1
SurveillaEnxccel.u...d..e..d.. .c.l.i.n..i.c..a..l. .e..f.f.e..c.t..i.v..e.n...e.s..s. .s..t.u..d..ies4 with
Managemraetniot.noaf.led is.e..a..s.e.......................................................................5.........211
J Burch,1* M Paulden,2 S Conti,2 C Stock,1
Chapter A2p pendix 4
DefinitioPnr ooft othcoe ld cehcaisnigoen p...r..o..b..l.e..m... ................................9.........213
M Corbett, 1 NJ Welton,3 AE Ades,3
Decision.problem.......................................... 9
OverAalpl.paeimndsi.xa n5d .objectives.of.the.assessment... 9 A Sutton,4 N Cooper,4 AJ Elliot,5
Quality assessment ......................................215
Chapter 3 K Nicholson,6 S Duffy,1 C McKenna,2
AsseAsspmpeenntd ioxf 6c linical effectiveness ............ 11
L Stewart,1 M Westwood,1 S Palmer2
MethodsF.foorre.rsetv pielowtisn g....c..l.i.n..i.c..a..l...e..f.f.e..c.t..i.v.e..n..e..s..s..................21311
Results.of.review.of.clinical.effectiveness...... 13
Appendix 7 1Centre for Reviews and Dissemination, University of York, UK
Chapter 4 Bayesian multi-parameter evidence synthesis with
2Centre for Health Economics, University of York, UK
Bayesiani nmduirleticpta croammpeaterris oenvisd e..n..c..e.. .s..y.n..t..h..e..s.i.s.. .o..f. .s.y..m...p2t5o1m
3Academic Unit of Primary Health Care, Department of Community Based
data with indirect comparisons .................. 67
Medicine, University of Bristol, UK
IntroAdpupcetinodni.x.. .8.. ............................................ 67
MethodsL.i..t.e..r..a..t.u..r..e.. .r.e..v..i.e..w.. .o..f.. .u..t.i.l.i.t.y.. .s.c..o..r..e..s. .f.or6 8influenza . 4Department of Health Sciences, University of Leicester, UK
Results.......................................................................................................................6..9..257 5Birmingham Research Unit of the Royal College of General Practitioners, UK
Discussion..................................................... 73 6Department of Infection, Immunity and Inflammation, University of
Appendix 9
Leicester, UK
Chapter 5 Detailed economic model inputs ................261
Assessment of cost-effectiveness evidence . . 75
*Corresponding author
SysteAmpapteicn.rdeixvi e1w0 . of.existing.cost-effectiveness.evidence..
...........w..i.n..b..u..g..s. .m....o..d..e..l. .t.o.. .e..s.t..i.m...a..t.e.. .t..h..e.. .p7r5obability that an
York.EcoInLoI mis iicn.Aflusseenszsma e..n...t.......................................................1..0..3.........265
Declaration of competing interests: AJ Elliot has received funding from the
Chapter H6 e alth Technology Assessment reports published to pharmaceutical industry to attend an influenza-related conference. No other authors declare
Discussiodna t.e.. ..................................................................................................1..3..9.........267 any competing interests.
Statement.of.principal.findings....................139
StrenHgethalst.han Tde.clihmniotlaotgioyn As.sosfe.tshsme.aesnste s sment.. . 141
Uncertaipnrtoiegsr.a..m...m...e.. ..........................................................................1..4..2.........287
Conclusions...................................................142 Published November 2009
DOI: 10.3310/hta13580
Acknowledgements ...........................................145
Contribution.of.authors................................145
This report should be referenced as follows:
Burch J, Paulden M, Conti S, Stock C, Corbett M, Welton NJ, et al. Antiviral drugs for the
treatment of influenza: a systematic review and economic evaluation. Health Technol Assess
2009;13(58).
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DOI: 10.3310/hta13580 Health Technology Assessment 2009; Vol. 13: No. 58
Abstract
Antiviral drugs for the treatment of influenza: a
systematic review and economic evaluation
J Burch,1* M Paulden,2 S Conti,2 C Stock,1 M Corbett,1 NJ Welton,3
AE Ades,3 A Sutton,4 N Cooper,4 AJ Elliot,5 K Nicholson,6 S Duffy,1 C
McKenna,2 L Stewart,1 M Westwood,1 S Palmer2
1Centre for Reviews and Dissemination, University of York, UK
2Centre for Health Economics, University of York, UK
3Academic Unit of Primary Health Care, Department of Community Based Medicine, University of
Bristol, UK
4Department of Health Sciences, University of Leicester, UK
5Birmingham Research Unit of the Royal College of General Practitioners, UK
6Department of Infection, Immunity and Inflammation, University of Leicester, UK
*Corresponding author
Objectives: To evaluate the clinical effectiveness Results: Amantadine was excluded at an early stage,
(including adverse events) and cost-effectiveness owing to a lack of any new trials that met the inclusion
of antivirals for the treatment of naturally acquired criteria and the limitations of the existing evidence.
influenza for ‘at-risk’ and otherwise healthy populations. The review therefore focused on the neuraminidase
Data sources: Eleven electronic databases (MEDLINE, inhibitors (NIs) oseltamivir and zanamivir, both of
EMBASE, Cumulative Index to Nursing and Allied which were found to be effective in reducing symptom
Health Literature, Pascal, Science Citation Index, duration (zanamavir by 0.5–1.0 days and oseltamivir
BIOSIS, Latin American and Caribbean Health Sciences, by 0.5–1.5 days). However, the effect sizes were often
Cochrane Database of Systematic Reviews, Cochrane small and unlikely to be clinically significant in many
Central Register of Controlled Trials, Database of cases, particularly in healthy adults. For the at-risk
Abstracts of Reviews of Effects, and Health Technology subgroups, effect sizes for differences in symptom
Assessment Database) were searched from October duration were generally larger, and potentially more
2001 to November 2007. A supplementary search was clinically significant, than those seen in healthy adults
undertaken in June 2008 for information relating to drug (median duration of symptoms reduced by 1–2 days
resistance during the 2007–8 influenza season. with zanamivir and 0.50–0.75 days with oseltamivir).
Review methods: Systematic reviews of the evidence However, there was greater uncertainty around
on the clinical effectiveness and cost-effectiveness these results, with estimates often failing to reach
of antivirals for the treatment of influenza were statistical significance. The most consistent data and
undertaken. Twenty-nine randomised controlled trials strongest evidence related to antibiotic use, with
comparing antivirals with each other, placebo, or best both zanamivir and oseltamivir resulting in statistically
symptomatic care were included in the evaluation of significant reductions in antibiotic use. In general, the
clinical effectiveness in patients presenting with an estimates from the cost-effectiveness model were
influenza-like illness (ILI). Primary outcomes were more favourable in at-risk populations (including
measures of symptom duration (median time to adults and children with comorbid conditions and the
alleviation of symptoms and median time to return to elderly) compared with otherwise healthy populations.
normal activity). Incidence of complications, mortality, Zanamivir was the optimal NI treatment in each of
hospitalisations, antibiotic use (as a surrogate for the at-risk populations considered, and oseltamivir
complications) and adverse events was also assessed. In was optimal for healthy populations (both adults and
addition, an independent decision model was developed children).
to evaluate the cost-effectiveness of antiviral treatment Conclusions: The clinical effectiveness data
from the perspective of the UK NHS. for population subgroups used to inform the
iii
© 2009 Queen’s Printer and Controller of HMSO. All rights reserved.
Abstract
multiparameter evidence synthesis and cost- some concerns, the use of NIs in at-risk populations
effectiveness modelling were, in places, limited and appeared to be a cost-effective approach for the
this should be borne in mind when interpreting the treatment of influenza. Well-designed observational
findings of this review. Trials were often not designed to studies might also be considered to evaluate the
determine clinical effectiveness in population subgroups clinical course of influenza in terms of complications,
and hence, although the direction of effect was clear, hospitalisation, mortality and quality of life, as well as the
estimates of differences in symptom duration tended to impact of NIs.
be subject to greater uncertainty in subgroups. Despite
iv
DOI: 10.3310/hta13580 Health Technology Assessment 2009; Vol. 13: No. 58
Contents
List of abbreviations .................................... vii Acknowledgements .....................................145
Executive summary ..................................... ix References ...................................................147
1 Background ................................................. 1 Appendix 1 Literature.search.strategies .....157
Description.of.health.problem .................... 1
Surveillance .................................................. 4 Appendix 2 Details.of.included.studies ......173
Management.of.disease ............................... 5
Appendix 3 Excluded.clinical.effectiveness.
2 Definition of the decision problem ............. 9 studies.with.rationale ...................................211
Decision.problem ......................................... 9
Overall.aims.and.objectives.of.the. Appendix 4 Protocol.change .......................213
assessment ............................................... 9
Appendix 5 Quality.assessment ..................215
3 Assessment of clinical effectiveness ............ 11
Methods.for.reviewing.clinical. Appendix 6 Forest.plots ..............................231
effectiveness ............................................. 11
Results.of.review.of.clinical.effectiveness ..... 13 Appendix 7 Bayesian.multi-parameter.
evidence.synthesis.with.indirect.
4 Bayesian multiparameter evidence comparisons .................................................251
synthesis of symptom data with indirect
comparisons ................................................. 67 Appendix 8 Literature.review.of.utility
Introduction ................................................. 67 scores.for.influenza ......................................257
Methods ....................................................... 68
Results .......................................................... 69 Appendix 9 Detailed.economic.model
Discussion .................................................... 73 inputs ...........................................................261
5 Assessment of cost-effectiveness Appendix 10 winbugs.model.to.estimate.the.
evidence ....................................................... 75 probability.that.an.ILI.is.influenza ..............265
Systematic.review.of.existing.
cost-effectiveness.evidence ...................... 75 Health Technology Assessment reports
York.Economic.Assessment ..........................103 published to date .........................................267
6 Discussion ....................................................139 Health Technology Assessment
Statement.of.principal.findings ...................139 programme ..................................................287
Strengths.and.limitations.of.the.
assessment ...............................................141
Uncertainties ...............................................142
Conclusions ..................................................142
v
© 2009 Queen’s Printer and Controller of HMSO. All rights reserved.

DOI: 10.3310/hta13580 Health Technology Assessment 2009; Vol. 13: No. 58
List of abbreviations
BNF British National Formulary EQ-5D EuroQoL.5-dimension.
measure.of.health-related.
CDC Centers.for.Disease.Control. quality.of.life
and.Prevention
FDA Food.and.Drug.Administration
CDSC Communicable.Disease.
Surveillance.Centre GCP good.clinical.practice
CEAC cost-effectiveness.acceptability. GI gastrointestinal
curve
GPRD General.Practice.Research.
CENTRAL. Cochrane.Central.Register.of. Database
Controlled.Trials
H1,.2.or.3 haemagglutinin.subtype.1,.2.
CHE Centre.for.Health.Economics or.3
CI confidence.interval HES hospital.episodes.statistics
CNS central.nervous.system HPA Health.Protection.Agency
COAD chronic.obstructive.airways. HRG Healthcare.Resource.Group
disease
HRQoL health-related.quality.of.life
CRD. Centre.for.Reviews.and.
Dissemination HTA. Health.Technology.Assessment
CrI credibility.interval HUI-3 Health.Utilities.Index.Mark.3
DARE. Database.of.Abstracts.of. ICER incremental.cost-effectiveness.
Reviews.of.Effects ratio
DH Department.of.Health ICU intensive.care.unit
DRG diagnosis-related.group ILI influenza-like.illness
ECDC European.Centre.for.Disease. ITT intention.to.treat
Prevention.and.Control
ITTI intention.to.treat,.infected.
ED extendedly.dominated (those.with.confirmed.
influenza)
EISS European.Influenza.
Surveillance.Scheme ITU intensive.therapy.unit
ELISA enzyme-linked.immunosorbent. MCMC Markov.Chain.Monte.Carlo
assay
MeSH medical.subject.headings.in.
the.MEDLINE.thesaurus
continued vii
© 2009 Queen’s Printer and Controller of HMSO. All rights reserved.
List of abbreviations
MOSA Medical.Officers.of.Schools. QALY quality-adjusted.life-year
Association
QoL quality.of.life
MVH Measurement.and.Valuation.of.
Health.study QWB quality.of.well-being
N1.or.2 neuraminidase.subtype.1.or.2 RCGP Royal.College.of.General.
Practitioners
N/A not.available
RCT randomised.controlled.trial
NAMCS National.Ambulatory.Medical.
Care.Survey RNA ribonucleic.acid
NI neuraminidase.inhibitor RSV respiratory.syncytial.virus
NIC National.Influenza.Centre RTI respiratory.tract.infection
NICE. National.Institute.for.Health. SARS severe.acute.respiratory.
and.Clinical.Excellence syndrome
NIVEL Netherlands.Institute.of. SAVE Simulating.Anti-influenza.
Primary.Health.Care Value.and.Effectiveness.model
NPHS National.Public.Health.Service ScHARR University.of.Sheffield.
School.of.Health.and.Related.
NRR. National.Research.Register Research
OR odds.ratio SPC summary.of.product.
characteristics
Os. oseltamivir
TA58 Technology.Assessment.No..58
OTC over-the-counter
TPR true-positive.rate
PCR polymerase.chain.reaction
TTO time.trade-off
Pl. placebo
VAS visual.analogue.scale
PSS Personal.Social.Services
WHO World.Health.Organization
PPV positive.predictive.value
WMD weighted.median.difference
QALD quality-adjusted.life-day
WRS weekly.returns.service
QALE quality-adjusted.life.expectancy
w.r.t. with.respect.to
All.abbreviations.that.have.been.used.in.this.report.are.listed.here.unless.the.abbreviation.is.well.
known.(e.g..NHS),.or.it.has.been.used.only.once,.or.it.is.a.non-standard.abbreviation.used.only.in.
figures/tables/appendices,.in.which.case.the.abbreviation.is.defined.in.the.figure.legend.or.in.the.
notes.at.the.end.of.the.table.
viii