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Cost effectiveness of darunavir/ritonavir 600/100mg bid in treatment-experienced, lopinavir-naive, protease inhibitor-resistant, HIV-infected adults in Belgium, Italy, Sweden and the UK |
Moeremans K, Hemmett L, Hjelmgren J, Allegri G, 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 highly active antiretroviral therapy (HAART) containing darunavir boosted with low-dose ritonavir, twice daily, compared with HAART containing lopinavir and low-dose ritonavir, twice daily, in treatment-experienced, lopinavir-naive, HIV-infected adults, with one or more mutation associated with protease inhibitor resistance. The authors concluded that the HAART regimen containing darunavir was cost-effective, from the perspectives of the Belgian, Italian, Swedish, and UK payers. The methods were valid, which makes the authors’ conclusions robust. Type of economic evaluation Cost-effectiveness analysis, cost-utility analysis Study objective This study assessed the cost-effectiveness of highly active antiretroviral therapy (HAART) including darunavir 600mg boosted with low-dose ritonavir 100mg, twice daily, compared with HAART including lopinavir 400mg boosted with low-dose ritonavir 100mg, twice daily, for treatment experienced, lopinavir naive, HIV infected adults, with one or more mutation associated with protease inhibitor resistance. Interventions The two treatments were HAART containing darunavir and HAART containing lopinavir. HAART included an optimised background regimen of two or more nucleoside reverse transcriptase inhibitors, with or without a non-nucleoside reverse transcriptase inhibitor. If either treatment failed, patients were given tipranavir plus ritonavir. Location/setting UK, Belgium, Italy, and Sweden/primary and secondary care. Methods Analytical approach:A published Markov model of HIV management, with a lifetime horizon, was used to simulate the treatment options. The authors stated that the analysis was carried out from the perspective of the public payer.
Effectiveness data:The clinical inputs were from a selection of relevant studies. The treatment effect and patients’ characteristics were from a subgroup of patients in a phase III clinical trial (TMC114/r In Treatment-Experienced Patients Naive to Lopinavir; TITAN). The data for tipranavir were from two trials (Randomized Evaluation of Strategic Intervention in Multi-drug Resistant Patients with Tipranavir; RESIST 1 and 2). Most of the evidence was already incorporated in the decision model and was from two published clinical trials (POWER 1 and 2). The rates of virological response were key inputs for the model. The long-term disease progression was based on an equation that prolonged the benefits and the discontinuation rates from the short-term data in the original model. HIV-related mortality was from observational studies. Some assumptions were needed.
Monetary benefit and utility valuations:The utility values were from published sources.
Measure of benefit:Life-years and quality-adjusted life-years (QALYs) were the summary benefit measures. The discount rates were 3.5% for the UK, 1.5% for Belgium, and 3% for Italy and Sweden.
Cost data:The economic analysis included the costs of the antiretroviral drugs and other in-patient and out-patient health care for the management of disease or treatment-related complications. The quantities of drugs were from the TITAN trial, and their unit costs were from local official sources. The other health care costs were estimated using data from local observational cost-of-care studies (Belgium, Italy, and Sweden) or published literature (UK). The 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 annual discount rates were 3% for Belgium, Italy, and Sweden, and 3.5% for the UK.
Analysis of uncertainty:Extensive one-way sensitivity analyses were carried out to investigate the uncertainty around the following inputs: the extent and duration of treatment-induced immune reconstitution, the drug use, the utilities, the costs, and the HIV-related mortality. One thousand Monte Carlo simulations were run, selecting inputs from probability distributions, based on published evidence. The discount rate and time horizon were varied. Results Compared with lopinavir, the darunavir regimen, in Belgium, led to increases of EUR 5,664 in costs, 0.751 life-years, and 0.785 QALYs. The incremental cost was EUR 7,278 per life-year gained or EUR 6,964 per QALY gained. In Italy, it led to increases of EUR 5,643 in costs, 0.572 life-years, and 0.608 QALYs. The incremental cost per life-year gained was EUR 9,858 and per QALY gained was EUR 9,277. In Sweden, it led to increases of EUR 4,013 in costs, 0.548 life-years, and 0.584 QALYs. The incremental cost per life-year gained was EUR 7,325 and per QALY gained was EUR 6,868. In the UK, it led to increases of EUR 8,122 in costs, 0.513 life-years, and 0.550 QALYs. The incremental cost per life-year gained was EUR 15,825 and per QALY gained was EUR 14,778.
In all countries, the most influential inputs were the rate of initial rapid cluster of differentiation (CD) 4 cell count increase, and the duration and rate of slow CD4 cell count increase or the period of CD4 cell count stabilisation before the switch. Even in unfavourable scenarios, the incremental cost per QALY gained generally remained below the commonly cited threshold of EUR 30,000 per QALY gained.
The incremental cost per QALY gained was below this EUR 30,000 threshold in more than 70% of simulations for each country. A time horizon of five years resulted in better cost-effectiveness ratios in Sweden, but worse values in the other three countries. In all cases, the incremental cost per QALY gained remained below EUR 40,000. Authors' conclusions The authors concluded that the HAART regimen containing darunavir boosted with low-dose ritonavir was cost-effective, compared with the lopinavir regimen, from the perspectives of the Belgian, Italian, Swedish, and UK payers. CRD commentary Interventions:The rationale for the selection of the comparators was clear. At the time of the study, the lopinavir regimen was the standard HAART for these patients, and the darunavir regimen was the proposed therapy.
Effectiveness/benefits:No systematic review was reported to identify the relevant sources of evidence. The sources were generally valid. Most of the evidence for the treatment effect was from a head-to-head clinical trial, which also defined the patients’ characteristics. The data for the tipranavir regimen were from two clinical trials. In general, randomised studies are considered to be robust sources of data due to their methods. Extrapolation of data to the long-term was based on an equation and authors’ assumptions; extensive sensitivity analyses were conducted on these assumptions and other uncertain parameters. QALYs and life-years were both appropriate benefit measures, which captured the burden of disease on the patients’ health. Limited information on the derivation of the utility values was provided.
Costs:The cost categories were consistent with the perspective adopted. The drug costs were presented and were from standard sources for each country, and their dosages were from clinical trials. Other health care costs were not itemised, but were reported for ranges of CD4 cell count; this approach is common in HIV-related studies. These costs were from a published study, the methods of which were not reported. Details, such as the price year and the discount rate, were reported. Alternative ranges of costs were considered in the sensitivity analyses. The costs were assigned probability distributions, which were reported and justified.
Analysis and results:The results were extensively presented. An incremental approach was used to synthesise the costs and benefits of each strategy. Valid approaches were used to investigate the uncertainty and the findings were clearly presented and discussed. The clinical and economic impact of adverse events was not considered, as the source trial showed no difference in safety between the two treatments. The decision model was presented and justified and appears to have been appropriate for a progressive disease. The results appear to be transferable to other European countries and similar findings were obtained from a US model. The authors acknowledged that a limitation of their analysis was that all patients switched to tipranavir after treatment failure, while other options were available.
Concluding remarks:The methods were valid, which makes the authors’ conclusions robust. Funding Financial support received from Johnson & Johnson Pharmaceutical Services, owner of Tibotec, manufacturer of darunavir. Bibliographic details Moeremans K, Hemmett L, Hjelmgren J, Allegri G, Smets E. Cost effectiveness of darunavir/ritonavir 600/100mg bid in treatment-experienced, lopinavir-naive, protease inhibitor-resistant, HIV-infected adults in Belgium, Italy, Sweden and the UK. PharmacoEconomics 2010; 28(Supplement 1): 147-167 Indexing Status Subject indexing assigned by NLM MeSH Adult; Antiretroviral Therapy, Highly Active /economics; Belgium; CD4 Lymphocyte Count /economics; Clinical Trials, Phase II as Topic; Cost-Benefit Analysis; Darunavir; Drug Resistance, Viral; Female; Great Britain; HIV Infections /drug therapy /economics /mortality /virology; HIV Protease Inhibitors /adverse effects /economics /therapeutic use; HIV-1 /drug effects; Health Care Costs; Humans; Italy; Lopinavir; Male; Markov Chains; Multicenter Studies as Topic; Pyrimidinones /adverse effects /economics /therapeutic use; Quality-Adjusted Life Years; RNA, Viral /blood; Randomized Controlled Trials as Topic; Ritonavir /adverse effects /economics /therapeutic use; Sulfonamides /economics /therapeutic use; Sweden; Viral Load /economics AccessionNumber 22011000279 Date bibliographic record published 05/10/2011 Date abstract record published 14/12/2011 |
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