Cost effectiveness of darunavir/ritonavir 600/100 mg bid in treatment-experienced, lopinavir-naive, protease inhibitor-resistant, HIV-infected adults in Belgium, Italy, Sweden and the UK.

BACKGROUND: Using data from the phase IIb POWER trials, darunavir boosted with low-dose ritonavir (DRV/r; 600/100 mg twice daily; bid)-based highly active antiretroviral therapy (HAART) was shown to be significantly more efficacious and cost effective than other protease inhibitor (PI)-based therapy in highly treatment-experienced, HIV-1-infected adults. Furthermore, in the phase III TITAN trial (TMC114-C214), DRV/r 600/100 mg bid-based HAART generated a superior 48-week virological response rate compared with standard-of-care lopinavir/ritonavir (LPV/r; 400/100 mg bid)-based therapy in treatment-experienced, lopinavir-naive patients, and in particular those with one or more International AIDS Society - USA (IAS-USA) primary PI resistance-associated mutations at baseline. These patients had a broader degree of previous PI use/failure (0 - ≥ 2) than the POWER patients. OBJECTIVES: To determine whether DRV/r 600/100 mg bid-based HAART is cost effective compared with LPV/r-based therapy, from the perspective of Belgian, Italian, Swedish and UK reimbursement authorities, when used in treatment-experienced patients similar to TITAN patients with one or more IAS-USA primary PI mutations at baseline. METHODS: An existing Markov model containing health states defined by CD4 cell count ranges (>500, 351-500, 201-350, 101-200, 51-100 and 0-50 cells/mm³) and an absorbing state of death was adapted for use in the above-mentioned healthcare settings. Baseline demographics, CD4 cell count distribution, antiretroviral drug usage, virological/immunological response rates and matching transition probabilities were based on data collected during the first 48 weeks of therapy in the modelled subgroup of TITAN patients and the published literature. After treatment failure, patients were assumed to switch to a follow-on combination regimen. For each health state, utility values and mortality rates were obtained from the published literature. Data from local observational studies (Belgium, Sweden and Italy) or the published literature (UK) were used to determine resource-use patterns and costs associated with each CD4 cell count range. Unit costs were derived from official local sources; a lifetime horizon was taken and discount rates were chosen based on local guidelines. RESULTS: The base-case analysis predicted quality-adjusted life year (QALY) gains of 0.785 in Belgium, 0.608 in Italy, 0.584 in Sweden and 0.550 in the UK when DRV/r-based therapy was used instead of LPV/r-based treatment. The estimated base-case incremental cost-effectiveness ratios (ICERs) were €6964/QALY gained in Belgium, €9277/QALY gained in Italy, €6868 (SEK69,687)/QALY gained in Sweden and €14,778 (£12 612)/QALY gained in the UK. Assuming a threshold of €30,000/QALY gained, DRV/r-based therapy remained cost effective over most parameter ranges tested in extensive one-way sensitivity analyses. The variation of immunological response rates and the time horizon were identified as important drivers of cost effectiveness. Probabilistic sensitivity analysis revealed a greater than 70% probability of achieving an ICER below this threshold in all four healthcare settings. CONCLUSION: From the perspective of Belgian, Italian, Swedish and UK payers, DRV/r 600/100 mg bid-based HAART is predicted to be cost effective compared with LPV/r 400/100 mg bid-based therapy, when used to manage treatment experienced, lopinavir-naive, PI-resistant, HIV-infected adults with a broad range of previous PI use/failure.

Predicting direct costs of HIV care during the first year of darunavir-based highly active antiretroviral therapy using CD4 cell counts: evidence from POWER.

BACKGROUND: Given the association between CD4 cell counts and HIV-related morbidity/mortality, new antiretroviral therapies could potentially lower the direct costs of HIV care by raising CD4 cell counts. OBJECTIVES: To predict the effects of the ritonavir-boosted, HIV protease inhibitor (PI) darunavir on the direct costs of care, while accounting for CD4 cell counts, during the first year of therapy in highly treatment-experienced, HIV-infected adults in different healthcare settings. METHODS: The mean annual per-patient cost of darunavir/ritonavir (DRV/r) and control PI-based highly active antiretroviral therapy (HAART) was calculated from the proportional use of antiretroviral agents in the DRV/r and control PI arms of the pooled POWER 1 and 2 trials, applying drug-acquisition costs for five healthcare settings. Non-antiretroviral-related costs by CD4 cell count, derived from non-interventional studies in the same settings, were applied to the POWER data (proportion of patients with CD4 cell counts in different strata at week 48) to estimate mean annual non-antiretroviral-related costs per patient in patients receiving DRV/r or control PI-based HAART during year 1. RESULTS: Across all settings, the mean annual per-patient cost of DRV/r-based treatment was 2-19% higher than that of control PI-based therapy during the first year of therapy. By raising CD4 cell counts, however, DRV/r-based regimens were predicted to lower mean annual non-antiretroviral-related costs by 16-38% compared with control PI-based therapy. When combined, the total annual per-patient cost of HIV care during the first year of therapy was estimated to be 7% lower in the DRV/r compared with the control PI arm using US data, 8% lower using Swedish data, budget neutral using UK and Belgian data and 5% higher using Italian data. CONCLUSIONS: Darunavir-based HAART may lower non-antiretroviral-related costs compared with control PI-based therapy in highly treatment-experienced, HIV-infected patients during the first year of therapy by improving patients' CD4 cell counts. These costs could partly/fully offset the increased acquisition cost of DRV/r in this patient population over the same period.

Analysis of costs by CD4 count category for the darunavir/r 600/100 mg bid and control protease inhibitor arms of the POWER 1 and 2 trials.

BACKGROUND: HIV-infected people with low CD4 counts are at higher risk of AIDS and incur increased health care costs from in-patient stays and medications. METHOD: In the POWER 1 and 2 trials, patients were treated with optimized nucleoside reverse transcriptase inhibitors and optional enfuvirtide (T-20), plus darunavir/ritonavir (DRV/r) or control protease inhibitor (PI). UK data on costs of care by CD4 count were combined with the data on antiretroviral treatment use and CD4 counts from the POWER trials to calculate expected health care costs. RESULTS: The mean annual UK cost of care (excluding antiretrovirals [ARVs]) was 23,780 pounds, 13,762 pounds, 7,032 pounds, and 7,032 pounds for patients with CD4 <50, 50-200, 200-350, and >350 cells/muL respectively. In the POWER trials, at week 48, the proportions of patients with CD4 counts in these categories were 7%, 36%, 29%, and 27% for the DRV/r arm versus 23%, 28%, 27%, and 22% for the control PI arm. The mean predicted annual per-patient cost of care was 11,170 pounds for DRV/r versus 12,873 pounds for control PI. CONCLUSION: By raising CD4 counts to levels where the risk of AIDS events is reduced, DRV/r treatment is predicted to lower patient care costs for ARV-experienced, HIV-infected individuals in the first year of treatment.

The cost-effectiveness of human papillomavirus screening for cervical cancer. A review of recent modelling studies.

We compared findings from recent studies modelling the cost-effectiveness of screening for cervical cancer using human papillomavirus (HPV) testing and alternative strategies. Data were standardized to facilitate comparison of costs per life year or costs per QALY gained in six studies. Absolute changes in costs, life years and QALYs for each strategy were normalized to a comparison with no screening. Costs were standardized to US$ in 2000 values. Most models assume screening starts at age 18 or 20 years. Assumed prevalence of HPV ranges from 10% for those aged 18 years to 20% for those aged 20-25 years and drops substantially after age 30. All except one model assume sensitivity to LSIL of 83% or higher. Two models distinguish the increasing specificity of HPV testing in older age groups (up to 95% for LSIL in women aged 55 years or older). All the models include consultation costs as well as screening and treatment costs, but costs for follow-up diagnosis and treatment vary considerably. Two models also include patient time costs. Despite these differences all strategies involving HPV testing have cost per quality-adjusted life-year (QALY) ratios in the range of USD 12,400-16,600. Costs per life year vary more widely, the highest being USD 19,246 (annual screening with liquid cytology and HPV). However, excluding strategies using liquid cytology, the highest costs per life year for a strategy including HPV testing are under USD 14,000 (simultaneous conventional cytology and HPV every two years). The cost per life year for HPV testing alone triennially is lower than for Pap smear testing alone biennially. Costs per QALY are generally lower than costs per life year (given the reported modelling assumptions and settings). Even with inclusion of patient costs, no strategies involving HPV testing cost more than USD 16,600 per QALY. Adoption of the ACOG guidelines to include HPV testing with cytology as a screening option for women aged 30 years or older therefore appears to be cost-effective.

A cost-effectiveness analysis of docetaxel in the second-line treatment of non-small cell lung cancer.

BACKGROUND: Whilst lung cancer is the most common form of cancer in England and Wales (annual incidence rate of 50 per 100,000) it does not always receive the policy attention accorded to other types of cancer, such as breast and colorectal. Nevertheless, the burden of lung cancer is significant and the UK NHS Plan for cancer has set out the government's commitment to improving all cancer services. The question faced by the NHS is which interventions are most cost effective in implementing this plan. OBJECTIVE: To develop a model to assess the economics of second-line treatment of non-small cell lung cancer (NSCLC) from the perspective of the UK NHS, based on the resources and outcomes from the pivotal clinical study comparing docetaxel 75 mg/m(2) with best supportive care (BSC). METHODS: The area under the survival curve for each treatment was analysed and the difference in mean survival between the docetaxel group and the BSC group was calculated as 3.82 months. Measurable incremental costs for the docetaxel group were largely driven by drug acquisition and administration. These cost drivers, as well as toxicity treatment costs and cost offsets, were varied in the sensitivity analysis. Although the overall timeframe for the model was 2 years, discounting was not applied as the resources and benefits of docetaxel use in this setting are realised relatively immediately. RESULTS: The base case cost-effectiveness analysis (mean values) reported a cost per life-year gained of 13,863 pounds sterling for docetaxel 75 mg/m(2) (year 2000/2001 values). Sensitivity analysis showed that the number of treatment cycles per patient, which affected total treatment cost, had most influence on the cost per life-year gained in the base case scenario. Using the 95% confidence intervals around the mean number of treatment cycles, the base case cost per life-year gained varied from 10,985 pounds sterling to 16,738 pounds sterling. Using the 95% confidence intervals around the mean difference in survival, to represent best and worst case scenarios, the cost per life-year saved ranged from 10,020 pounds sterling to 32,781 pounds sterling . CONCLUSION: This model suggests, with its underlying assumptions and data, docetaxel 75 mg/m(2) in 3-weekly cycles is a cost-effective second-line treatment, from the perspective of the NHS, for pretreated NSCLC in terms of survival gains made for a reasonable increase in costs.