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Cost effectiveness of darunavir/ritonavir 600/100mg bid in protease inhibitor-experienced, HIV-1-infected adults in Belgium, Italy, Sweden and the UK |
Moeremans K, Annemans L, Lothgren M, Allegri G, Wyffels V, Hemmet L, Caekelbergh K, Smets E |
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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 This study assessed the cost-effectiveness of darunavir boosted with low-dose ritonavir, as part of a regimen for treatment-experienced patients with HIV-1 in four European countries. The authors concluded that it was cost-effective, from the perspective of the payer in each country, compared with control protease inhibitor regimens, for patients who had failed to respond to more than one protease inhibitor regimen. Methodologically, the study was well conducted and it was satisfactorily presented. The authors’ conclusions appear to be robust. Type of economic evaluation Cost-effectiveness analysis, cost-utility analysis Study objective This study assessed the cost-effectiveness of darunavir boosted with low-dose ritonavir, for treatment-experienced patients with HIV-1, in four European countries. Interventions The two interventions were highly active antiretroviral therapies. One included darunavir 600mg with ritonavir 100mg, twice daily, plus an optimised background regimen, with or without enfuvirtide. This was compared with other protease inhibitors, plus the optimised background regimen, with or without enfuvirtide. If any treatment failed, it was assumed that patients were switched to tipranavir plus ritonavir. Location/setting UK, Belgium, Italy, and Sweden/primary and secondary care. Methods Analytical approach:The analysis used a published US Markov model, in which the health states were defined by ranges of the patients' cluster of differentiation (CD) 4 cell counts. This was adapted for each country. A lifetime horizon was considered. The authors stated that the analysis was carried out from the perspective of the health care system.
Effectiveness data:The clinical data were from a selection of relevant studies. Most of the inputs were those used in the original US model, which were from two independent, multinational, phase IIb, randomised controlled trials (POWER 1 and 2). These two trials provided the characteristics of the patients and the short-term virological response rate, which was a key endpoint of the treatments. The long-term disease progression was from observational studies and other published sources. The efficacy of tipranavir plus ritonavir was from two clinical trials, with similar patients to those of POWER 1 and 2. HIV-related mortality was from the EuroSIDA cohort study database. Country-specific life tables were used.
Monetary benefit and utility valuations:The utility values were from a study that transformed European Quality of life (EQ-5D) questionnaire scores, from 21,000 HIV trial participants, into utility weights using a published preference weight method.
Measure of benefit:Quality-adjusted life-years (QALYs) and life-years were the summary benefit measures. The discount rate was 3.5% for the UK, 1.5% for Belgium, and 3% for Italy and Sweden.
Cost data:The economic analysis included the costs of antiretroviral drugs and in-patient and out-patient disease monitoring and management of disease or treatment-related complications. Drug usage was based on clinical trial data, with unit costs from local official sources. Other costs were from observational cost-of-care studies. All costs were in Euros (EUR), converted from local currency for the UK and Sweden. The price year was 2008 for the UK and 2009 for Belgium, Italy, and Sweden. The discount rate was 3.5% for the UK, 3% for Belgium, Italy, and Sweden.
Analysis of uncertainty:Extensive one-way sensitivity analyses were carried out on the key inputs (efficacy, drug use, utilities, costs, and HIV-related mortality). A probabilistic sensitivity analysis was carried out, using Monte Carlo simulation, by assigning probability distributions to the model inputs. The following scenarios were analysed: varying the time horizon, varying the discount rate, changing the time from the start of the CD4 cell count decline until enfuvirtide treatment interruption or therapy switch, using tipranavir plus ritonavir as an initial comparator, and switching to control protease inhibitors instead of tipranavir upon treatment failure. Results Compared with the control treatments, the darunavir regimen, in Belgium, increased the costs by EUR 16,049 and increased the benefits by 1.387 life-years or 1.397 QALYs. The incremental cost per life-year gained was EUR 11,568 and per QALY gained was EUR 11,484. In Italy, it led to increases of EUR 14,197 in costs, 1.146 life-years, and 1.171 QALYs. The incremental cost per life-year gained was EUR 12,386 and per QALY gained was EUR 12,122. In Sweden, it led to increases of EUR 12,495 in costs, 1.114 life-years, and 1.142 QALYs. The incremental cost per life-year gained was EUR 11,213 and per QALY gained was EUR 10,942. In the UK, it led to increases of EUR 17,933 in costs, 1.061 life-years, and 1.091 QALYs. The incremental cost per life-year gained was EUR 16,908 and per QALY gained was EUR 16,438.
The most influential inputs were the rate of initial CD4 cell count increase, the duration and rate of slow increase or stable CD4 cell count, and the mortality. The costs of HIV care were influential in Italy and Sweden.
The incremental cost per QALY was below the threshold of EUR 30,000 in 95% of simulations in Belgium, 97% in Italy, 92% in Sweden, and 78% in the UK.
With a five-year time horizon the darunavir regimen was dominant, as it was less costly and more effective, in all countries. Compared with the tipranavir regimen, darunavir had an incremental cost per QALY of EUR 15,542 in Belgium, EUR 9,926 in Italy, EUR 10,907 in Sweden, and EUR 18,388 in the UK. Authors' conclusions The authors concluded that the darunavir regimen was cost-effective, from perspective of the payer in the four European countries, compared with control protease inhibitor regimens, for the treatment of patients who had failed to respond to more than one protease inhibitor regimen. CRD commentary Interventions:The comparators were selected on the basis of the regimens included in the POWER trials. The tipranavir regimen was not included, in the base case, as it was newly approved and not commercially available at the time of the trials. It was considered in the sensitivity analyses.
Effectiveness/benefits:No systematic review was reported to identify the sources of evidence for each country. Most of the evidence came from head-to-head multinational clinical trials, which are generally valid and robust sources due to their methods. An indirect comparison was needed for tipranavir in the sensitivity analysis, but the sources for this had very similar populations, which should reduce any bias. The long-term data were from standard sources for HIV models. Additional epidemiological inputs were from country-specific databases. An extensive sensitivity analysis was conducted on all the clinical parameters and alternative scenarios were assessed. Both the benefit measures were appropriate for capturing the impact of the disease on the patients’ health. Conventional discounting was applied to the expected survival. The utility values for the QALYs were from a large sample of patients.
Costs:The cost categories reflected the perspective of the health care sector, as stated by the authors. Details on the sources of costs were presented for each country, enhancing the transparency of the analysis. The unit costs and resource use were presented separately for some items, and the total costs for each health state were reported for every country. The authors appropriately used local sources for resource use and although these were based on different populations and designs, they produced similar costs. Details, such as the price year and discount rate, were reported. Probability distributions were applied to the costs and these distributions were reported. The economic analysis was conducted satisfactorily.
Analysis and results:Extensive analyses were performed on the projected costs and benefits, which were synthesised using an incremental approach. Appropriate deterministic and probabilistic sensitivity analyses were carried out to determine if the base case findings were robust, and the results were clearly illustrated and discussed. A clear description of the model was provided. The authors acknowledged some potential limitations of their analysis and these mainly related to uncertainty in the long-term clinical parameters, but these were extensively tested in the sensitivity analyses. The results are likely to be transferable to other European countries, given the similarity in findings for the four countries analysed.
Concluding remarks:Methodologically, the study was well conducted and it was satisfactorily presented. The authors’ conclusions appear to be robust. Funding Funding received from Johnson & Johnson Pharmaceutical Services, and Janssen Cilag (Italy, Belgium, and Sweden), part of the Johnson & Johnson group, owner of Tibotec, manufacturer of darunavir. Bibliographic details Moeremans K, Annemans L, Lothgren M, Allegri G, Wyffels V, Hemmet L, Caekelbergh K, Smets E. Cost effectiveness of darunavir/ritonavir 600/100mg bid in protease inhibitor-experienced, HIV-1-infected adults in Belgium, Italy, Sweden and the UK. PharmacoEconomics 2010; 28(Supplement 1): 107-128 Indexing Status Subject indexing assigned by NLM MeSH Adult; Antiretroviral Therapy, Highly Active /economics; CD4 Lymphocyte Count /economics; Cost-Benefit Analysis; Darunavir; Female; Great Britain; HIV Infections /drug therapy /economics /virology; HIV Protease Inhibitors /economics /therapeutic use; HIV-1 /drug effects /physiology; Health Care Costs; Humans; Italy; Male; Markov Chains; Quality-Adjusted Life Years; RNA, Viral /blood; Randomized Controlled Trials as Topic; Ritonavir /economics /therapeutic use; Sulfonamides /economics /therapeutic use; Sweden AccessionNumber 22011000277 Date bibliographic record published 05/10/2011 Date abstract record published 14/12/2011 |
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