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US cost effectiveness of darunavir/ritonavir 600/100mg bid in treatment-experienced, HIV-infected adults with evidence of protease inhibitor resistance included in the TITAN trial |
Brogan A, Mauskopf J, Talbird SE, 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 plus low-dose ritonavir, compared with HAART containing lopinavir plus low-dose ritonavir, for the management of treatment-experienced, HIV-infected adults with one or more genetic mutation associated with protease inhibitor resistance. The authors concluded that the darunavir regimen was cost-effective, from a societal perspective, in the USA. The methods were valid and various areas of uncertainty were considered. 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 highly active antiretroviral therapy (HAART) containing darunavir plus low-dose ritonavir, compared with HAART containing lopinavir plus low-dose ritonavir, for the management of treatment-experienced, HIV-infected adults with one or more genetic mutation associated with protease inhibitor resistance. Interventions Both HAART regimens included an optimised background regimen of two or more nucleoside reverse transcriptase inhibitors (NRTIs), with or without a non-nucleoside reverse transcriptase inhibitor (NNRTI). These were chosen on the basis of each patient’s treatment history and resistance profile. Darunavir 600mg plus ritonavir 100mg, given twice daily, was compared with lopinavir 400mg plus ritonavir 100mg, given twice daily. In both cases, it was assumed that tipranavir plus ritonavir was given if treatment failed. Location/setting USA/primary and secondary care. Methods
Analytical approach:The analysis was based on a published Markov model containing health states defined by cluster of differentiation (CD) 4 cell count ranges. A lifetime horizon was considered and the authors stated that a societal perspective was adopted.
Effectiveness data:The clinical data were from a selection of clinical trials and observational studies. The short-term efficacy of the two treatments and the baseline patients’ characteristics were from a phase III, head-to-head clinical trial (TMC114/r In Treatment-Experienced Patients Naive to Lopinavir; TITAN). The data for tipranavir were from the Randomized Evaluation of Strategic Intervention in Multi-drug Resistant Patients with Tipranavir (RESIST) 1 and 2 trials. The long-term transition probabilities were calculated from cohort study data, using assumed regressions. HIV mortality was from international cohort studies and general mortality was from US life tables. The rate of virologic response and the duration of phases of CD4 count response were key inputs to the model.
Monetary benefit and utility valuations:The utility values were from the original model, which used data from a published study.
Measure of benefit:Quality-adjusted life-years (QALYs) and life-years were the summary benefit measures and were discounted at an annual rate of 3%.
Cost data:The economic analysis included the costs of the HAART drugs and health care, including treatment of opportunistic infections, prophylactic and other out-patient drugs, hospital stays, emergency department visits, out-patient visits, and terminal care. The health care costs were from a published US cost study. The drug costs were based on recommended dosages or those used in clinical trials, and their average wholesale prices. The cost of terminal care was from a published study. All costs were in US dollars ($) and the price year was 2008. A 3% annual discount rate was applied.
Analysis of uncertainty:One-way and probabilistic sensitivity analyses were carried out to examine the uncertainty. The ranges of values and distributions were from the TITAN trial and published sources. The results of the one-way analyses were presented in a tornado diagram. The probabilistic analysis used Monte Carlo simulation. Alternative scenarios were considered for the time horizon, discount rate, time until discontinuation of enfuvirtide, and the duration of the initial therapy. Results Compared with lopinavir, darunavir led to a gain of 0.461 life-years or 0.493 QALYs, and an additional cost of $11,358, over a lifetime. The incremental cost per life-year gained was $24,654 and per QALY gained it was $23,057.
The incremental cost per QALY gained remained below the threshold of $50,000 in all the sensitivity analyses. The most influential inputs were the rate of CD4 cell count change during the period of decline, the probability of death from HIV, the rate of CD4 cell count change during the period of stability or slow change, and other inputs related to the efficacy of treatment.
Shorter time horizons had more favourable cost-effectiveness ratios, with the lowest being $4,919 at 10 years. Reducing the total time on initial therapy before switching produced the largest cost per QALY at $32,986.
The probability of darunavir being below the cost-effectiveness threshold of $50,000 per QALY was 0.754. Authors' conclusions The authors concluded that the darunavir regimen was cost-effective, compared with the lopinavir regimen, from a societal perspective, in the USA. CRD commentary
Interventions:The selection of the comparators was appropriate. The authors stated that HAART regimens containing lopinavir were the standard care for HIV patients.
Effectiveness/benefits:No systematic review was reported to identify the relevant sources of evidence, but most of the evidence was from a head-to-head clinical trial, which also provided the patient characteristics, and this appears to have been valid. The data for tipranavir were from two other clinical trials. In general, randomised trials are considered to be valid sources of data due to their methods. Well-known studies of HIV patients were used for the additional inputs. Extensive sensitivity analysis was conducted on uncertain parameters and model assumptions. QALYs and life-years were both appropriate benefit measures, as they capture the burden of HIV and AIDS on patients’ health. Limited information on the derivation of the utility values was provided.
Costs:The authors stated that a societal perspective was adopted, but only the direct costs of the treatments were included. They stated that indirect costs were not considered as they were captured in the QALY estimates, and this was as recommended in US cost-effectiveness guidelines. The costs were generally presented as category totals and reported for each health state. The unit costs and resource quantities were not presented separately. Their sources appear to have been appropriate for the USA, but they were not fully described. The costs were treated stochastically and the distributions applied were reported. Details, such as the price year and discount rates, were given.
Analysis and results:The results were extensively presented. An incremental approach was used to synthesise the costs and benefits of the alternative strategies. Valid methods were used to assess uncertainty and the findings were clearly reported and discussed. The authors stated that the model did not consider adverse events as they were not significantly different between groups. The results appear to be specific to the US context and their transferability was not discussed.
Concluding remarks:The methods were valid and various areas of uncertainty were considered. The authors’ conclusions appear to be robust. Funding Funded by Johnson & Johnson Pharmaceutical Services, owner of Tibotec, a division of Janssen-Cilag and manufacturer of darunavir. Bibliographic details Brogan A, Mauskopf J, Talbird SE, Smets E. US cost effectiveness of darunavir/ritonavir 600/100mg bid in treatment-experienced, HIV-infected adults with evidence of protease inhibitor resistance included in the TITAN trial. PharmacoEconomics 2010; 28(Supplement 1): 129-146 Indexing Status Subject indexing assigned by NLM MeSH Adolescent; Adult; Aged; Antiretroviral Therapy, Highly Active /economics; CD4 Lymphocyte Count; Cost-Benefit Analysis; Darunavir; Disease Progression; Drug Resistance; Female; HIV /drug effects /physiology; HIV Infections /drug therapy /economics /mortality /virology; HIV Protease Inhibitors /administration & Health Care Costs; Humans; Male; Middle Aged; Quality-Adjusted Life Years; Ritonavir /administration & Sulfonamides /administration & Time Factors; United States; Viral Load /economics; Young Adult; dosage /economics /therapeutic use; dosage /economics /therapeutic use; dosage /economics /therapeutic use AccessionNumber 22011000278 Date bibliographic record published 05/10/2011 Date abstract record published 03/02/2012 |
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