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Shortened peginterferon and ribavirin treatment for chronic hepatitis C |
Hartwell D, Jones J, Baxter L, Shepherd J |
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Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. CRD summary The objective was to assess the cost-effectiveness of shortened versus standard pegylated interferon-alpha and ribavirin treatment, for chronic hepatitis C virus, in patients who were eligible for shortened treatment. The authors concluded that shortened treatment could be viable. The methods were good, and the results were generally well reported. Given the scope of the analysis, the authors’ conclusions appear to be appropriate. Type of economic evaluation Study objective Standard treatment with pegylated interferon-alpha and ribavirin (or monotherapy for those unable to tolerate ribavirin) was compared with shorter treatment, for patients with chronic hepatitis C. Interventions Patients who achieved a rapid response after four weeks of pegylated interferon-alpha, with or without ribavirin, were eligible for shorter treatment. Those with genotype one received 24 weeks of treatment, and those with genotypes two or three received 16 weeks of treatment. This was compared with the usual length of treatment, which was 48 weeks for genotype one, and 24 weeks for genotypes two or three. Methods Analytical approach:A published Markov model was adapted to estimate the cost-effectiveness of the two options (Shepherd, et al. 2007, see Other Publications of Related Interest). The time horizon was the lifetime of the patient. The authors reported that the UK NHS and personal social services (PSS) perspective was adopted. Effectiveness data:The clinical and effectiveness data were from published studies, conferences and symposia, industry submissions, or clinical experts. The published studies were identified by a systematic search of the literature from 2000 to October 2009, in fourteen databases, including The Cochrane Library, MEDLINE and EMBASE. Randomised controlled trials evaluating the two options were included. The quality of the trials was assessed by two reviewers independently. The data were synthesised in a narrative and not meta-analysed due to variation in the data. The main measures of effectiveness were the virologic response, relapse rate, and adverse events. Monetary benefit and utility valuations:The utility estimates were identified by the literature review, and were from one randomised controlled trial, which used the EQ-5D to elicit them. Measure of benefit:Quality-adjusted life-years (QALYs) were the benefit measure. Future benefits were discounted at an annual rate of 3.5%. Cost data:The direct costs were those of the drugs; monitoring; patient management whilst on antiviral treatment; liver transplantation; and the health states of relapse, chronic hepatitis C, cirrhosis, and hepatocellular carcinoma. The drug unit costs were from the 2009 British National Formulary. The costs of monitoring and management were from a published economic evaluation. The health state costs were from an observational study conducted alongside a trial. The liver transplantation costs were from a UK study. All costs were reported in UK £, at 2007 to 2008 prices. Future costs were discounted at an annual rate of 3.5%. Analysis of uncertainty:One-way sensitivity analyses were undertaken to assess the areas that were most uncertain and had the most impact on the results. A probabilistic sensitivity analysis was conducted to assess parameter uncertainty, with distributions assigned to the main estimates. The details of the probabilistic analysis were reported in Hartwell, et al. (2011, see Other Publications of Related Interest). Results Depending on the source trial, for patients with genotype one, the QALYs ranged from 15.68 to 19.74 for standard treatment, and from 15.54 to 20.03 for short treatment. The costs ranged from £14,206 to £26,169 for standard treatment, and from £8,994 to £17,173 for short treatment. Compared with standard pegylated interferon-alpha-2a and ribavirin for 48 weeks, short 24-week treatment had an incremental cost per QALY gained of £34,510 or £64,880. Compared with standard pegylated interferon-alpha-2b and ribavirin, short treatment was dominant, as it was cheaper and more effective. For genotypes two or three, the QALYs were 15.31 or 15.64 for standard treatment, and 15.54 or 15.72 for short treatment. The costs were £7,834 or £10,089 for standard treatment, and £5,728 or £6,943 for short treatment. Compared with standard pegylated interferon-alpha-2a and ribavirin for 24 weeks, short 16-week treatment was dominant, using either set of data. The probabilistic sensitivity analysis showed that for genotype one, short treatment with pegylated interferon-alpha-2a was cost-effective in at least 83% of simulations, at a willingness-to-pay threshold of £20,000 and 59% of simulations at a threshold of £30,000 per QALY gained. For genotypes two or three, short treatment was cost-effective in 100% of simulations. Authors' conclusions The authors concluded that shortened pegylated interferon and ribavirin therapy could be a viable treatment. CRD commentary Interventions:The interventions were reported clearly. Their selection was appropriate as they were relevant options for patients with chronic hepatitis C in the UK. Effectiveness/benefits:The methods used to obtain the clinical and effectiveness estimates were reported in detail. A thorough literature review was conducted in 14 databases, and all studies were assessed by two independent reviewers; it is likely that all relevant information was included. The inclusion and exclusion criteria were reported, and unpublished trials were sought, including in industry submissions and conference or symposia abstracts. QALYs were appropriately used as the summary benefit measure; they capture the global impact of the interventions on patient health and allow comparisons with the benefits of other health care interventions. The methods used to derive the utility weights and their values were reported. Costs:The perspective was explicitly reported to be that of the NHS and PSS. For this perspective, it seems that all the relevant major costs were included. The sources for these costs were reported. The individual cost items were not listed, and the resource quantities were not given separately from their unit costs, which would have made it easier to replicate the analysis. The price year, time horizon and discount rate were all reported. Analysis and results:The authors adapted a published Markov model to synthesise the cost and outcome information. The details of the model structure were reported, but no diagram was provided. The impact of uncertainty on the results was adequately tested in one-way and probabilistic sensitivity analyses. As the main limitation to their study, the authors reported that some of the effectiveness data were from very small clinical trials. Concluding remarks:The methods were good, and the results were generally well reported. Given the scope of the analysis, the authors’ conclusions appear to be appropriate. Funding Funding received from the UK NIHR Health Technology Assessment programme. Bibliographic details Hartwell D, Jones J, Baxter L, Shepherd J. Shortened peginterferon and ribavirin treatment for chronic hepatitis C. International Journal of Technology Assessment in Health Care 2012; 28(4): 398-406 Other publications of related interest Shepherd J, Jones J, Hartwell D, et al. Interferon alfa (pegylated and non-pegylated) and ribavirin for the treatment of mild chronic hepatitis C: a systematic review and economic evaluation. Health Technology Assessment 2007; 11: 1-205. Hartwell D, Jones J, Baxter L, Shepherd J. Peginterferon alfa and ribavirin for chronic hepatitis C in patients eligible for shortened treatment, re-treatment or in HCV/HIV co-infection: a systematic review and economic evaluation. Health Technology Assessment 2011; 15(17): 1-210. Indexing Status Subject indexing assigned by NLM MeSH Antiviral Agents /therapeutic use; Drug Therapy, Combination /economics; Great Britain; Health Care Costs; Hepacivirus /drug effects; Hepatitis C, Chronic /drug therapy /economics /genetics; Humans; Interferon-alpha /therapeutic use; Markov Chains; Polyethylene Glycols; Quality-Adjusted Life Years; Ribavirin /therapeutic use AccessionNumber 22012040639 Date bibliographic record published 31/01/2013 Date abstract record published 26/02/2013 |
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