Health benefits of antiviral therapy for mild chronic hepatitis C

132 Pages·2006·0.61 MB·English

H Health Technology Assessment 2006;Vol. 10: No. 21
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July 2006
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Health benefits of antiviral therapy
for mild chronic hepatitis C:
randomised controlled trial and
economic evaluation
1 2 2 1
M Wright, R Grieve, J Roberts, J Main and
1*
HC Thomas on behalf of the UK Mild Hepatitis C
Trial Investigators
1 Department of Medicine, St Mary’s Hospital, London, UK
2 Collaborative Centre for Economics of Infectious Disease, Health Services
Research Unit, Department of Public Health and Policy, London School of
Hygiene and Tropical Medicine, UK
* Corresponding author
Declared competing interests of authors:none
Published July 2006
This report should be referenced as follows:
Wright M, Grieve R, Roberts J, Main J, Thomas HC on behalf of the UK Mild Hepatitis C
Trial Investigators. Health benefits of antiviral therapy for mild chronic hepatitis C:
randomised controlled trial and economic evaluation. Health Technol Assess2006;10(21).
Health Technology Assessmentis indexed and abstracted in Index Medicus/MEDLINE,
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Health Technology Assessment2006; Vol. 10: No. 21
Abstract
Health benefits of antiviral therapy for mild chronic hepatitis C:
randomised controlled trial and economic evaluation
M Wright,1 R Grieve,2 J Roberts,2 J Main1 and HC Thomas1* on behalf of the
UK Mild Hepatitis C Trial Investigators
1Department of Medicine, St Mary’s Hospital, London, UK
2Collaborative Centre for Economics of Infectious Disease, Health Services Research Unit, Department of Public
Health and Policy, London School of Hygiene and Tropical Medicine, UK
* Corresponding author
Objectives: To determine whether combined therapy at 12 weeks achieved an SVR. HRQoL fell during
with interferon-(cid:2)and ribavirin was more effective and treatment and rose with treatment cessation. For
cost-effective than no treatment for patients with mild patients having an SVR there were modest
chronic hepatitis C. improvements in HRQoL at 6 months post-treatment.
Design: A multicentre, randomised, controlled, non- The mean cost per QALY gained was £4535 for 40-
blinded trial assessed the efficacy of combination year-old patients with genotype non-1 and £25,188 for
therapy. A Markov model used these efficacy data patients with genotype 1. For patients with genotype 1
combined with data on transition probabilities, costs aged 65, providing interferon-(cid:2)and ribavirin for mild
and health-related quality of life (HRQoL) to assess the disease led to fewer QALYs gained, and a mean cost
lifetime cost-effectiveness of the intervention. per QALY of £53,017. The model using efficacy
Setting: A multicentre NHS setting. estimates from the literature, showed that the cost per
Participants: Treatment-naive, adult patients with QALY gained from providing pegylated interferon (cid:2)-2b
histologically mild chronic hepatitis C (Ishak and ribavirin at a mild stage rather than a moderate
necroinflammatory scores <4 and fibrosis scores <3 stage was £7821 for patients with genotype non-1 and
on liver biopsy). £28,409 for patients with genotype 1.
Interventions: Patients were randomised to receive Conclusions: Based on the evidence collected in this
interferon-(cid:2)and ribavirin for 48 weeks or no study, interferon-(cid:2)and ribavirin treatment for mild
treatment (control). chronic hepatitis C patients is in general cost-effective
Main outcome measures: The primary outcome at the £30,000 per QALY threshold previously used by
measure was the proportion of patients having a policy-makers in the NHS. For patients with chronic
sustained virological response (SVR), measured at hepatitis C aged 65 or over with genotype 1, antiviral
6 months after cessation of therapy. Secondary treatment at a mild stage does not appear cost-
outcome measures were: the ability of early phase effective. Further research is required on the cost-
kinetics to predict the eventual outcome of treating effectiveness of pegylated interferon and ribavirin, in
mild disease; HRQoL measured using the Short Form particular the intervention’s long-term impact on
36 and EuroQol (5 Dimensions) questionnaires, and the HRQoL and health service costs requires further
cost per quality-adjusted life-year (QALY) of interferon- evaluation. Further research is also needed to develop
(cid:2)and ribavirin for mild disease compared with no predictive tests, based on pharmacogenomics, that can
treatment. identify those cases most likely to respond to antiviral
Results: In the treatment group, 32 out of 98 patients therapy. Liver biopsy before treatment no longer
(33%) achieved an SVR. Patients infected with appears justified apart from for older patients (aged 65
genotype 1 had a lower SVR than those infected with or over) with genotype 1. However, further research
genotype non-1 (18% versus 49%, p= 0.02). No should monitor the impact this strategy would have on
patients who failed to achieve a 2-log drop in viral load costs and outcomes.
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Health Technology Assessment2006; Vol. 10: No. 21
Contents
List of abbreviations .................................. vii 6 HRQoL for different stages of
hepatitis C .................................................. 55
Executive summary .................................... ix Introduction ............................................... 55
Methods ...................................................... 55
1 Introduction ............................................... 1 Results ........................................................ 56
The scale of the hepatitis C virus Discussion ................................................... 60
epidemic ..................................................... 1
Clinical perspective .................................... 2 7 Results of the cost-effectiveness
Currently available antiviral therapies ....... 2 analysis ....................................................... 63
Aims of the study ....................................... 5 Introduction ............................................... 63
Base-case cost-effectiveness:
2 Design of the RCT ..................................... 7 definition and analytical method ............... 63
Introduction ............................................... 7 Base-case cost-effectiveness
Study population ........................................ 7 results ......................................................... 64
Treatment of the study group .................... 8 Parameter uncertainty due to different
Management of adverse events .................. 10 patient characteristics ................................. 65
Study medication ....................................... 11 Uncertainty surrounding methodological
Health-related quality of life ...................... 11 assumptions ................................................ 68
(cid:2)
Virology ...................................................... 12 Pegylated interferon- and
Statistical plan and methods ...................... 12 ribavirin ...................................................... 69
Summary of findings .................................. 71
3 Results of the RCT ..................................... 15
Patient numbers and characteristics at trial 8 Discussion ................................................... 73
baseline ....................................................... 15 Introduction ............................................... 73
Virological end-points ................................ 18 Methodological and management issues
Early viral kinetics and treatment encountered in the trial ............................. 73
outcome ...................................................... 18 Results of the RCT ..................................... 74
Effect of antiviral treatment on HRQoL ... 22 HRQoL ....................................................... 76
Adverse events and dose modifications ..... 25 Adverse events ............................................ 78
Histopathology ........................................... 78
4 Cost-effectiveness model for mild The cost-effectiveness model ..................... 78
hepatitis C: structure and transition
probabilities ............................................... 27 9 Conclusions ................................................ 83
Introduction ............................................... 27 Recommendations for further
Cost-effectiveness analyses in research ...................................................... 83
hepatitis C .................................................. 27
Overview of the methodology for the Acknowledgements .................................... 87
CEA ............................................................ 28
Model structure .......................................... 29 References .................................................. 89
Early transition probabilities ...................... 30
Other transition probabilities .................... 35 Appendix 1 HRQoL data .......................... 95
Discussion ................................................... 36
Appendix 2 Quantitative virology ............. 103
5 The costs of different stages of
hepatitis C .................................................. 39 Appendix 3 Statistical methods for
Introduction ............................................... 39 estimation of transition rates ..................... 107
Costing methodology ................................. 39
Results ........................................................ 44 Appendix 4 Unit costs used in the cost
Discussion and conclusions ........................ 50 analysis ....................................................... 109
v
Contents
Appendix 5 Parameters for probabilistic Health Technology Assessment
model ......................................................... 113 Programme ................................................ 127
Health Technology Assessment reports
published to date ....................................... 115
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Health Technology Assessment2006; Vol. 10: No. 21
List of abbreviations
ALT alanine aminotransferase M male
ANA antinuclear antibodies MCS mental component summary
score
ANCOVA analysis of covariance
MCV mean corpuscular volume
ANOVA analysis of variance
MRC Medical Research Council
AUC area under the curve
MREC multicentre research ethics
BNF British National Formulary
committee
CEA cost-effectiveness analyses
MRI magnetic resonance imaging
CEAC cost-effectiveness acceptability
NA not applicable
curve
NB net benefit
CI confidence interval
NICE National Institute for Health and
CRF case-report form
Clinical Excellence
CT computed tomography
ns not significant
DGH district general hospital
OLS ordinary least squares
EOTR end of treatment response
OR odds ratio
EQ-5D EuroQol 5 Dimensions
PCR polymerase chain reaction
F female
PCS physical component summary
(cid:3)
GGT -glutamyltransferase score
HAI Histological Activity Index PPV positive predictive value
Hb haemoglobin QALY quality-adjusted life-year
HbA1c glycosylated haemoglobin RBC red blood cell
HBsAg serum hepatitis B surface antigen RCS Royal College of Surgeons
HCC hepatocellular carcinoma RCT randomised controlled trial
HCV hepatitis C virus RFLP restriction fragment length
polymorphism
HDU high-dependency unit
ROC receiver operating characteristic
HRQoL health-related quality of life
SD standard deviation
ICER incremental cost-effectiveness
ratio SF-36 Short Form 36
INR international normalised ratio SVR sustained virological response
IPA Inflammation, Parenchymal TIPPS transjugular intrahepatic
damage, Architecture portosystemic shunt
ITT intention to treat TSH thyroid-stimulating hormone
IVDU intravenous drug use ULN upper limit of normal
LREC local research ethics committee WBC white blood cell
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 at the end of the table.
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