Cost-Effectiveness of Ivabradine in the Treatment of Chronic Heart Failure.

BACKGROUND: In the Systolic Heart failure treatment with the If inhibitor Trial (SHIFT) randomised placebo-controlled trial, ivabradine was shown to reduce hospital admissions for worsening heart failure (HF) and deaths due to HF in patients with symptomatic systolic HF and an elevated resting heart rate (HR). This analysis evaluates the cost effectiveness of adding ivabradine to optimal standard HF treatment in patients with a HR≥77 bpm. METHODS: A Markov model was developed to assess the impact of ivabradine on mean survival and quality of life over a patient's lifetime (10 years). The hospitalisation and death rates were calculated using patient-level data from SHIFT. The reduction in quality of life due to HF hospitalisations was estimated directly from EQ-5D data collected in SHIFT. Australian costs were applied to the resource use from SHIFT. RESULTS: The modelled mean increase in survival with ivabradine was 0.115 years. The mean increase in quality-adjusted survival was 0.108 years. The average cost of ivabradine was A$2,957 and the cost savings associated with a reduction in HF hospitalisations was A$1,344. The cost per quality adjusted life year gained (QALYG) was A$14,905. The conservative approach to the modelled evaluation, as well as results of the sensitivity analysis, demonstrates that ivabradine is likely to be cost-effective in this indication. CONCLUSIONS: The conservative approach to the modelled evaluation, as well as results of the sensitivity analysis, demonstrates that ivabradine is a cost-effective treatment in the Australian setting for HF patients with a HR≥77 bpm on optimal standard therapy with a cost per QALYG similar or lower than that for other publicly funded treatments.

A Decision-Analytic Model to Assess the Cost-Effectiveness of Etelcalcetide vs. Cinacalcet.

INTRODUCTION: Etelcalcetide is a novel intravenous calcimimetic for the treatment of secondary hyperparathyroidism (SHPT) in haemodialysis patients. The clinical efficacy and safety of etelcalcetide (in addition to phosphate binders and vitamin D and/or analogues [PB/VD]) was evaluated in three phase III studies, including two placebo-controlled trials and a head-to-head study versus the oral calcimimetic cinacalcet. OBJECTIVE: The objective of this study was to develop a decision-analytic model for economic evaluation of etelcalcetide compared with cinacalcet. METHODS: We developed a life-time Markov model including potential treatment effects on mortality, cardiovascular events, fractures, and subjects' persistence. Long-term efficacy of etelcalcetide was extrapolated from the reduction in parathyroid hormone (PTH) in the phase III trials and the available data from the outcomes study in cinacalcet (EVOLVE trial). Etelcalcetide was compared with cinacalcet, both in addition to PB/VD. We applied unit costs averaged from five European countries and a range of potential etelcalcetide pricing options assuming parity price to weekly use of cinacalcet and varying it by a 15 or 30% increase. RESULTS: Compared with cinacalcet, the incremental cost-effectiveness ratio of etelcalcetide was €1,355 per QALY, €24,521 per QALY, and €47,687 per QALY for the three prices explored. The results were robust across the probabilistic and deterministic sensitivity analyses. CONCLUSIONS: Our modelling approach enabled cost-utility assessment of the novel therapy for SHPT based on the observed and extrapolated data. This model can be used for local adaptations in the context of reimbursement assessment.

Modelling the cost effectiveness of rituximab in chronic lymphocytic leukaemia in first-line therapy and following relapse.

BACKGROUND: The efficacy and safety of adding rituximab to fludarabine and cyclophosphamide (R-FC) for the treatment of chronic lymphocytic leukaemia (CLL) has been demonstrated in two randomised trials: CLL-8 was conducted in previously untreated patients, and REACH was conducted in previously treated patients. In both trials, progression-free survival was increased in the R-FC treatment groups compared with the FC treatment groups. In CLL-8, overall survival was also significantly increased. OBJECTIVE: To develop an economic model to assess the cost effectiveness, from the Australian healthcare perspective, of rituximab when used as a treatment for both previously untreated and relapsed/refractory CLL. METHODS: A Markov model with three health states (unprogressed, progressed and death) was developed to extrapolate the trial results over a 15-year time horizon. A treatment algorithm was developed with Australian haematologists to inform the treatments to be modelled. The base-case compares up to three courses of six cycles of R-FC ('first-line' treatment) followed by three courses of post-progression salvage ('Salvage') treatment (including rituximab) with three courses of FC followed by three courses of Salvage treatment (excluding rituximab). Subsequent treatments are incorporated into the model by repeating the unprogressed and progressed health states for each treatment. Time-dependent transition probabilities for the model were estimated from an analysis of individual patient data from CLL-8 and REACH. Comparisons of the hazard rates for the CLL-8 and REACH trials enabled an assessment of the impact on the transitions of receiving the same regimen as the first or second treatment, and hence inform assumptions regarding transitions for third and subsequent treatments. Costs applied in the model were based on published Australian prices in 2009. RESULTS: The model predicts patients receive an average of approximately two courses of treatment, and the addition of rituximab results in an incremental gain of 0.94 quality-adjusted life-years (QALYs). The incremental cost associated with the addition of rituximab is A$40,268, and hence the cost per QALY gained (QALYG) is A$42,906. CONCLUSION: Rituximab, in combination with chemotherapy, when used multiple times throughout the treatment algorithm, appears to be cost effective for CLL from the Australian healthcare perspective, with a cost/QALYG within the range generally accepted as providing value.

Cost-effectiveness of 12-month treatment with ticagrelor compared with clopidogrel in the management of acute coronary syndromes.

BACKGROUND: The PLATO (Platelet Inhibition and Patient Outcomes) randomized trial (NCT00391872) in patients with acute coronary syndromes (ACS) reported that ticagrelor (in addition to aspirin) reduced the rate of the composite end point of myocardial infarction (MI), stroke, or cardiovascular death compared with clopidogrel (in addition to aspirin) by 16% over 12 months (P < 0.001). No significant difference in the incidence of major bleeding was noted, but ticagrelor was associated with a higher rate of major bleeding not related to coronary artery bypass grafting. OBJECTIVE: By extrapolating the key findings of PLATO, we sought to assess the cost-effectiveness of ticagrelor compared with clopidogrel in the management of ACS in a contemporary Australian setting. METHODS: A Markov model with 4 health states (free from further ACS events, MI, stroke, and death) was developed to simulate the long-term costs and outcomes associated with ACS. Event risks were based on data derived directly from PLATO, and costs and utilities were drawn from published sources. A 10-year time horizon was simulated, and future costs and benefits were discounted at a 5% annual rate. However, treatment with ticagrelor and clopidogrel was only assumed for the first 12 months, with no benefits applied beyond drug cessation. Sensitivity analyses were undertaken based on variations to key data inputs. All costs for resource use applied in the analysis were based on published Australian prices (in 2010/2011 dollars [A$]). RESULTS: Over 10 years, the estimated quality-adjusted life-years lived per-patient were 5.74 and 5.68 for ticagrelor and clopidogrel, respectively. Net costs were A$19,132 for ticagrelor and A$18,428 for clopidogrel. These equated to an incremental cost-effectiveness ratio of A$9031 per quality-adjusted life-year gained for ticagrelor compared with clopidogrel. Sensitivity analyses indicated the result to be robust. CONCLUSIONS: When assessed from the perspective of the Australian health care system, ticagrelor is likely to be cost-effective compared with clopidogrel in preventing downstream morbidity and mortality associated with ACS.

Use of simulation to compare the performance of minimization with stratified blocked randomization.

Minimization is an alternative method to stratified permuted block randomization, which may be more effective at balancing treatments when there are many strata. However, its use in the regulatory setting for industry trials remains controversial, primarily due to the difficulty in interpreting conventional asymptotic statistical tests under restricted methods of treatment allocation. We argue that the use of minimization should be critically evaluated when designing the study for which it is proposed. We demonstrate by example how simulation can be used to investigate whether minimization improves treatment balance compared with stratified randomization, and how much randomness can be incorporated into the minimization before any balance advantage is no longer retained. We also illustrate by example how the performance of the traditional model-based analysis can be assessed, by comparing the nominal test size with the observed test size over a large number of simulations. We recommend that the assignment probability for the minimization be selected using such simulations.

Persistency rates for prostaglandin and other hypotensive eyedrops: population-based study using pharmacy claims data.

BACKGROUND: Effective management of ocular hypertension requires patients to be persistent with their treatment regimen. We evaluated patients' persistency with hypotensive eyedrops commonly used to treat glaucoma and ocular hypertension. METHODS: This large, population-based, retrospective, cohort study used pharmacy claims data for concessional patients from the Australian Pharmaceutical Benefits Scheme (July 1999-June 2005). Resupply rates for prostaglandins, beta-blockers, alpha-agonists and carbonic anhydrase inhibitors were analysed using life tables and Cox regression. Two populations, based on patients' supply histories, were examined: (i) 'new to this eyedrop'- patients who had used other hypotensive eyedrops before (presumably, previously diagnosed with glaucoma or ocular hypertension); and (ii) 'new to any eyedrop'- patients who were using their first hypotensive eyedrop (presumably, newly diagnosed with glaucoma or ocular hypertension). RESULTS: Data were obtained for 14,359,618 supplies of commonly used hypotensive eyedrops to 357,099 concessional patients. For both populations, resupply rates were highest for prostaglandins or the dorzolamide-timolol combination eyedrops, compared with beta-blockers, alpha-agonists or carbonic anhydrase inhibitors. Among the prostaglandins, there was no significant difference in the risk of ceasing supply between latanoprost and bimatoprost, but the risk was significantly higher for travoprost. CONCLUSIONS: Based on resupply rates from a national pharmacy claims database, patients supplied with ocular hypotensive eyedrops were most persistent with prostaglandin (bimatoprost, latanoprost and travoprost) and dorzolamide-timolol combination eyedrops. Among the prostaglandins, persistency was highest with, and similar between, bimatoprost and latanoprost. Persistency should be taken into account when selecting the most appropriate eyedrop to treat glaucoma and ocular hypertension.