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Cost effectiveness of darunavir/ritonavir in highly treatment-experienced, HIV-1-infected adults in the USA |
Mauskopf J, Brogan A, Martin S, 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 co-administered with low-dose ritonavir, compared with other protease inhibitors, for treatment-experienced HIV-1 patients in the USA. The authors concluded that darunavir plus ritonavir was likely to be cost-effective, for patients who had failed to respond to antiretroviral therapy. The study used valid methods, considered alternative assumptions, and investigated various areas of uncertainty. The authors’ conclusions are 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, compared with other protease inhibitors, for treatment-experienced HIV-1 patients in the USA. Interventions The two interventions were darunavir plus ritonavir and an optimised background regimen versus control protease inhibitors plus the optimised background regimen. The protease inhibitors included lopinavir boosted with ritonavir, amprenavir, atazanavir, saquinavir, indinavir, nelfinavir, and boosting dosages of ritonavir. Darunavir 600mg plus ritonavir 100mg was given twice daily. If any treatment failed, it was assumed that tipranavir plus ritonavir was given. Location/setting USA/primary and secondary care. Methods
Analytical approach:The analysis was based on a Markov model. Two time horizons were considered: five years and lifetime. The authors stated that a societal perspective was adopted.
Effectiveness data:The clinical data were from a selection of relevant studies. The baseline population characteristics and short-term treatment effect were from two clinical trials (POWER 1 and 2), the results of which were pooled. These data were used to estimate the transition probabilities for darunavir and the other protease inhibitors in the short-term. The virologic response at 24 weeks from the beginning of each treatment regimen was a key input for the model. Long-term disease progression was from observational studies and other published sources. The efficacy of tipranavir plus ritonavir was from two clinical trials, with a similar patients to those in POWER 1 and 2. Mortality data were from official databases and US life tables. Some assumptions were needed.
Monetary benefit and utility valuations:The utility weights were from a published study that used the European Quality of life (EQ-5D) instrument in HIV clinical trial participants that included US patients.
Measure of benefit:Quality-adjusted life-years (QALYs) and life-years were the summary benefit measures. They were discounted at an annual rate of 3%.
Cost data:The economic analysis included the costs of the drugs, in-patient and out-patient care, emergency department visits, and other medications. The drug dosages were from the POWER 1 and 2 clinical trials, while the unit costs were their average wholesale prices. Mark-up and dispensing fees were not considered. The costs of HIV care, including end-of-life care, were from published sources. All costs were in US dollars ($) and were discounted at an annual rate of 3%. The price year was 2008.
Analysis of uncertainty:Extensive one-way sensitivity analyses were carried out to test the impact of varying individual inputs on the model outcomes, using realistic ranges of values from published sources. A comprehensive probabilistic analysis used Monte Carlo simulation with distributions assigned to the efficacy, drug use, utility, cost, and mortality parameters. Alternative scenarios were considered. For example, tipranavir plus ritonavir as a first-line treatment was compared with darunavir plus ritonavir. Results In the five-year analysis, the life-years were 4.17 with darunavir, and 4.02 with control protease inhibitors. The QALYs were 3.80 with darunavir and 3.60 with control treatment. The costs were $217,288 with darunavir and $218,962 with control treatment. Darunavir was dominant, as it was more effective and less expensive than control treatment.
In the lifetime analysis, the life-years were 11.12 with darunavir and 9.86 with control treatment. The QALYs were 10.03 with darunavir and 8.76 with control treatment. The costs were $565,358 with darunavir and $527,287 with control treatment. The incremental cost per life-year gained was $30,436 with darunavir over control treatment and the incremental cost per QALY gained was $30,046.
In the five-year model, the most influential inputs were, in descending order, the rate of change in cluster of differentiation (CD) 4 cell count during the period of stability or slow increase, the duration of the period of stable or slowly increasing CD4 cell count, the HIV mortality, and the costs of medical resources other than the antiretroviral drugs.
In the lifetime model, the most influential inputs were the rate of CD4 cell count decline after virologic failure, the rate of CD4 cell count change during the period of stability or slow increase, the HIV mortality, and the duration of the period of rapidly increasing CD4 cell count.
In all scenarios and simulations, the incremental cost per QALY gained remained below the threshold of $50,000. The probability of being below this threshold was 0.921 in the five-year model and 0.950 in the lifetime simulation. In a scenario analysis, the incremental cost per QALY gained for darunavir, compared with tipranavir, was $32,709 over a lifetime. Authors' conclusions The authors concluded that darunavir plus ritonavir was likely to be cost-effective, compared with other protease inhibitors, for patients who had failed to respond to antiretroviral therapy. CRD commentary
Interventions:The selection of the comparators was based on the regimens used in the POWER trials. Ritonavir-boosted tipranavir was not included as it was not available at the start of these trials, but it was in use in the USA at the time of this study and it was included in a scenario analysis.
Effectiveness/benefits:The treatment effect data for the short-term were from head-to-head randomised clinical trials, which should have had high internal validity. Indirect comparison was needed for the scenario analysing tipranavir, but the source studies had very similar patient samples, which should have reduced any bias. The data for the long-term analysis were from standard sources for HIV models. An extensive sensitivity analysis was conducted on all the clinical parameters and alternative scenarios were analysed. In general, the clinical analysis was conducted satisfactorily. QALYs and life-years were appropriate benefit measures as they capture the impact of the interventions on the patients’ health. Outcome measures, such as the CD4 cell count ranges, were also reported.
Costs:The authors stated that the study was carried out from the perspective of society, but the analysis focused on the direct medical costs. The authors stated that indirect costs were not included as they were assumed to have been captured in the QALY estimates. Some costs were reported as category totals and the resource quantities and costs were not presented separately. Medication quantities were from clinical trials, which are likely to have recorded detailed information, but might not have fully reflected clinical practice. Other data were from published US studies, but these were not fully described. The unit costs were generally from standard US sources. The costs were treated stochastically and the distributions assigned were reported. Details, such as the discount rate and price year, were reported.
Analysis and results:The results were extensively presented and an incremental approach was used to synthesise the costs and benefits of the two strategies. The uncertainty was satisfactorily investigated, using various approaches, and the results were clearly presented and discussed. It was noted that the model did not consider the impact of treatment-related adverse events on health and costs, as these adverse events were not significantly different between treatments. The authors stated that the model parameters were specific to the US setting and would not be transferable to other settings, but the model could be adapted for other countries. It was pointed out that a key element of the analysis was the time horizon.
Concluding remarks:The study used valid methods, considered alternative assumptions, and investigated various areas of uncertainty. The authors’ conclusions are robust. Funding Funded by Johnson & Johnson Pharmaceutical Services, Belgium, owner of the company that manufactures darunavir. Bibliographic details Mauskopf J, Brogan A, Martin S, Smets E. Cost effectiveness of darunavir/ritonavir in highly treatment-experienced, HIV-1-infected adults in the USA. PharmacoEconomics 2010; 28(Supplement 1): 83-105 Indexing Status Subject indexing assigned by NLM MeSH Adult; Aged; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Clinical Trials as Topic; Cost-Benefit Analysis; Darunavir; Female; HIV Infections /drug therapy /economics /epidemiology /virology; HIV Protease Inhibitors /economics /therapeutic use; HIV-1; Health Care Costs; Humans; Male; Middle Aged; Quality-Adjusted Life Years; RNA, Viral /blood; Ritonavir /economics /therapeutic use; Sulfonamides /economics /therapeutic use; Treatment Outcome; United States /epidemiology; Young Adult AccessionNumber 22011000276 Date bibliographic record published 05/10/2011 Date abstract record published 03/02/2012 |
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