Cost-Effectiveness of Inotuzumab Ozogamicin Compared to Standard of Care Chemotherapy for Treating Relapsed or Refractory Acute Lymphoblastic Leukaemia Patients in Norway and Sweden.

OBJECTIVE: The aim was to estimate the cost-effectiveness of inotuzumab ozogamicin (InO) versus standard of care chemotherapy (SoC) for adults with relapsed or refractory B cell acute lymphoblastic leukaemia (R/R ALL) in Sweden and Norway, and compare this to evaluations made by the health technology assessment (HTA) authorities Tandvårds- och läkemedelsförmånsverket (TLV) and the Norwegian Medicines Agency (NoMA). MATERIALS AND METHODS: A partitioned survival model was developed to determine incremental cost-effectiveness ratios (ICERs) for InO versus SoC. Parametric survival models were fit to overall survival and progression-free survival Kaplan-Meier data from the INO-VATE ALL phase III trial. Two base cases were run using (1) Swedish and (2) Norwegian inputs (costs and discount rates). Core clinical inputs and utilities did not differ between countries. Analyses were then conducted to reflect the preferred assumptions of TLV and NoMA. Univariate and multivariate sensitivity analyses were performed. RESULTS: The base case deterministic ICERs for InO versus SoC were €16,219/quality-adjusted life years (QALY) in Sweden (probabilistic €19,415) and €44,405/QALY in Norway (probabilistic €47,305). The ICERs using our model but applying the preferred assumptions of TLV or NoMA were €74,061/QALY (probabilistic €77,484) and €59,391/QALY (probabilistic €63,632), respectively. Differences between our base cases and the ICERs with TLV and NoMA settings were mainly explained by the exclusion of productivity costs and use of pooled post-haematopoietic stem-cell transplant (post-HSCT) survival in Sweden and use of higher HSCT costs in Norway. All ICERs remained below the approximated willingness-to-pay thresholds. The probability of InO being cost-effective ranged from 77 to 99% versus SoC. CONCLUSIONS: InO can likely be considered cost-effective versus SoC under our and the HTA-preferred settings.

Cost-Effectiveness of Bosutinib for the Treatment of Adult Patients with Chronic Phase Chronic Myeloid Leukemia in the Second-Line Setting.

BACKGROUND: A recently conducted matching-adjusted indirect comparison demonstrated that bosutinib improved progression-free survival, and delayed progression to advanced disease compared with dasatinib and nilotinib in patients with second line (2L) chronic-phase chronic myeloid leukemia (CP-CML). However, the long-term clinical and economic impact of using bosutinib versus dasatinib and nilotinib has not been evaluated. The objective was to determine the cost-effectiveness of bosutinib compared with dasatinib and bosutinib compared with nilotinib from a US payer perspective. METHODS: A cost-effectiveness model was developed using partition survival methods and three health states: progression-free, progression, and death. Trial data (individual patient-level and aggregate-level data) informed the progression-free and overall survival estimates. Costs included drugs and medical resource use. Utility values were obtained from literature. Sensitivity analyses (SAs) included one-way and probabilistic sensitivity analyses (PSAs). RESULTS: Comparing bosutinib versus dasatinib resulted in a gain of 0.4 discounted life years, 1.5 quality-adjusted life years (QALYs), and incremental costs of $28,459 (values in 2020 US dollars), for an incremental cost-effectiveness ratio (ICER) of $19,811/QALY gained. Comparing bosutinib versus nilotinib resulted in a gain of 0.8 discounted life-years, 1.8 QALYs, and incremental costs of $76,563, for an ICER of $41,932/QALY gained. Drug costs and extrapolation distribution type were the main drivers of the model in the one-way SAs. In the PSAs, bosutinib had >90% and >80% probabilities of being cost-effective at a willingness-to-pay threshold of $100,000/QALY versus dasatinib and nilotinib, respectively. CONCLUSIONS: Our results suggest that compared with dasatinib and nilotinib, bosutinib may represent good value for money for treating 2L CP-CML patients.

Cost-Effectiveness Analysis of Aripiprazole Augmentation Treatment of Patients with Major Depressive Disorder Compared to Olanzapine and Quetiapine Augmentation in Turkey: A Microsimulation Approach.

OBJECTIVES: Major depressive disorder (MDD) is a chronic illness associated with a major burden on quality of life (QOL) and health care resources. Aripiprazole augmentation to antidepressant treatment was recently approved for patients with MDD responding insufficiently to antidepressant treatment in Turkey. The objective was to estimate the cost-effectiveness of aripiprazole augmentation in this indication compared with olanzapine and quetiapine augmentation from a payer perspective. METHODS: A lifetime economic model was built simulating transitions of patients with MDD between major depressive episodes (MDEs) and remission. During MDEs, patients were treated with adjunctive aripiprazole, quetiapine, or olanzapine. Patients who did not respond switched to subsequent treatment lines. Comparative effectiveness between adjunctive aripiprazole, quetiapine, and olanzapine was estimated by using an indirect comparison. Resource utilization and costs were obtained from Turkish studies. RESULTS: Over a lifetime horizon, patients treated with aripiprazole spent less time in MDEs than did patients treated with quetiapine (-11 weeks) and olanzapine (-7 weeks). On average, patients treated with aripiprazole showed improvement in QOL compared with patients treated with quetiapine (+0.054 quality-adjusted life-years [QALYs]) and olanzapine (+0.039 QALYs) combined with cost saving of 593 Turkish lira (TL) versus quetiapine and 485 TL versus olanzapine. The probability that adjunctive aripiprazole would be cost-effective among the three strategies ranged between 74% and 75% for willingness-to-pay values between 0 TL and 100,000 TL per QALY gained. CONCLUSIONS: This is the first lifetime health-economic model in Turkey that takes patient heterogeneity into account when assessing QOL and costs of different adjunctive strategies in MDD. The results indicate that adjunctive treatment with aripiprazole provides health benefits at lower costs in patients with MDD when compared with quetiapine and olanzapine augmentation.

The cost-effectiveness of paliperidone extended release in Spain.

BACKGROUND: Paliperidone Extended Release OROS (ER) is a new atypical antipsychotic for the treatment of schizophrenia. The objective is, based on a previously published model, to analyze the clinical and economic effects of Paliperidone ER in a Spanish setting compared to olanzapine oral and aripiprazole. METHODS: An existing discrete event simulation model was adapted to reflect the treatment of schizophrenia in Spain in terms of costs, resource use, and treatment patterns. Inputs for the model were derived from clinical trial data, literature research, database analysis and interviews with local clinical experts. The time horizon is 5 years and Spanish discount rate was applied. Outputs include direct medical costs and Quality Adjusted Life-Years (QALYs). Extensive sensitivity analyses were carried out to assess the robustness of the results, using ordinary least squares analysis and cost-effectiveness scatter plots. RESULTS: The results show that the mean incremental QALYs (95% CI) compared to olanzpine is 0.033 [-0.143, 0.304] and compared to aripiprazole 0.029 [-0.107, 0.300]. The corresponding mean incremental costs and corresponding confidence intervals are -€1425 [-€10,247, €3084] and -€759 [-€10,479, €3404], respectively. The probability that paliperidone ER is cost-saving and health gaining compared to olanzapine and aripiprazole is 76% and 72%, respectively. Paliperidone ER was estimated to have 80% and 81% probability of being cost-effective compared to olanzapine at a willingness to pay of €20,000 and €30,000 and 73% and 74% compared to aripiprazole, respectively. LIMITATIONS: Some of the modeled inter-relationships had to be based on expert opinion due to a lack of information. Also, foreign sources for the disutility of adverse events had been used due to a lack of Spanish data. Prolactin-related side-effects, indirect costs, and potential compliance advantages of paliperidone ER were not considered. It is unlikely that these limitations affected the conclusions. CONCLUSION: Based on differences in drug acquisition costs, side-effects, and risk of relapse, the model predicts that, in the Spanish healthcare setting, paliperidone ER dominates oral olanzapine and aripiprazole, with a probability of 76% and 72%, respectively.

Cost-effectiveness of clopidogrel in STEMI patients in the Netherlands: a model based on the CLARITY trial.

OBJECTIVE: This study assesses the costs and effects of combination treatment with clopidogrel and aspirin in comparison to aspirin alone in patients with an ST-segment elevation myocardial infarction (STEMI) in a Dutch setting. METHODS: A decision tree model is used to combine data from different sources about efficacy, epidemiology and costs. In the short-run, cost-effectiveness is based on efficacy data derived from the CLARITY trial. The cost-effectiveness of continued treatment is addressed by analysing which conditions need to be fulfilled to deem the strategy 'cost-effective', and discussing whether it is likely that it is. Estimates concerning the benefits of preventing events are derived from Swedish registries. Approximations of both direct and indirect costs are derived from the literature. Effects are expressed as life years gained and Quality Adjust Life Years (QALYs). Uncertainties are addressed by uni- and multivariate sensitivity analyses with and without taking account of the dependency between the separate ischaemic events. RESULTS: A treatment regimen similar to that of the CLARITY trial, including patients similar to those in the trial, is estimated to result in 0.05 additional life years and 0.062 additional quality adjusted life years for a cost that is euro1929 lower than aspirin therapy. Continuation of treatment outside the trial period is expected to result in ICERs of below euro20,000 per QALY as long as the real risk reduction of combination treatment is greater than 0.487% per year. CONCLUSION: The results indicate that clopidogrel therapy combined with aspirin, according to the regimen seen in CLARITY, and using data from Swedish registries to inform the model, is cost-effective. Sensitivity analyses suggest that the model is robust to a wide range of parameter estimates, including those based on data from Swedish registries. Continued treatment is very likely to be cost effective in light of all the indirect evidence.

Economic evaluation of zoledronic acid for the prevention of osteoporotic fractures in postmenopausal women with early-stage breast cancer receiving aromatase inhibitors in the UK.

BACKGROUND: Aromatase inhibitors are used as adjuvant therapy for breast cancer (BC) and are associated with accelerated bone loss. Zoledronic acid (ZOL) prevents aromatase inhibitor-associated bone loss (AIBL) in postmenopausal women with BC. This analysis assessed the cost-effectiveness of ZOL for prevention of fractures in postmenopausal women with BC. MATERIALS AND METHODS: A Markov model was developed to project lifetime incidence of fractures, quality-adjusted life years (QALY), and costs as a function of bone mineral density (BMD) for women with early-stage BC receiving letrozole alone or with ZOL. Two strategies of ZOL therapy were compared with no treatment: starting ZOL treatment only when BMD levels decreased ('delayed ZOL') and starting ZOL simultaneously with letrozole therapy ('upfront ZOL'). RESULTS: Delayed ZOL therapy was estimated to cost 16,069 pounds per QALY, when compared with not administering bisphosphonates for AIBL prevention. The corresponding cost per QALY gained for upfront ZOL versus no treatment was estimated at 21,973 pounds. The cost-effectiveness ratio for upfront versus delayed therapy was estimated at 24,868 pounds per QALY gained. CONCLUSION: Both delayed and upfront therapy with ZOL for the prevention of AIBL and fractures in BC patients in the UK appear to result in highly acceptable cost-effectiveness ratios.

Efficacy of recombinant activated factor VII vs. activated prothrombin complex concentrate for patients suffering from haemophilia complicated with inhibitors: a Bayesian meta-regression.

The optimal on-demand treatment of joint bleeds in haemophilia patients with inhibitors is a source of debate, with studies reporting various efficacy levels for different drugs and dosage regimens. To analyse, in a unified Bayesian meta-regression model, the published efficacy of recombinant activated factor VII (rFVIIa) and/or activated prothrombin complex concentrate (aPCC) as on-demand treatments for joint bleeds in haemophilia patients with inhibitors. A systematic search was carried out to identify studies reporting on dosage and efficacy of rFVIIa and aPCC in the treatment of joint bleeds in the target patient population. Data were abstracted and included in the model and adjusted for potential sources of heterogeneity. Pooled efficacy levels for typical rFVIIa and aPCC regimens were estimated. Seventeen studies, collectively reporting on >2000 joint bleeds, were included. Medication type combined with dosage was the only significant explanatory parameter. The model predicts that a typical regimen of 90 microg kg(-1) rFVII repeated every 3 h if needed results in cumulative joint bleed resolution of 66%, 88% and 95% after 12, 24 and 36 h, respectively. In comparison, a typical regimen of 75 IU kg(-1) aPCC repeated every 12 h if needed results in cumulative joint bleed resolution of 39%, 62% and 76%, respectively. These differences were statistically significant and were also robust in sensitivity analyses. This analysis suggests that a typical rFVIIa regimen will resolve joint bleeds more effectively than a typical aPCC regimen after 12, 24 and 36 h.

Cost-effectiveness and budget impact of long-acting risperidone in Portugal: a modeling exercise.

BACKGROUND: Previous analyses have shown that long-acting risperidone (LAR) is cost-effective in several Western countries. In Portugal, however, the costs of key services are lower. Therefore, available evidence in other countries may have limited relevance. OBJECTIVE: To estimate costs and effects of LAR versus a conventional depot and a short-acting oral atypical antipsychotic over a 5-year period in Portugal. METHODS: An existing discrete event model was adapted to reflect the Portuguese healthcare setting, based on expert opinion, clinical, epidemiological, and cost data. The model compares three scenarios. In scenario 1, patients start with a conventional depot; in scenario 2, with LAR; and in scenario 3, with oral risperidone. The model simulates individual patient histories while taking into account patient characteristics such as risk to society and side-effects. Subsequently, the model simulates patient histories in terms of outpatient appointments, psychotic episodes, treatment, compliance, symptom scores, lack of ability to take care presenting an actual risk, and treatment setting. Outcomes were number of psychotic episodes, cumulative symptom score and direct medical costs. Univariate sensitivity analyses were carried out. RESULTS: Compared to a conventional depot and an oral atypical, LAR was estimated to save approximately euro 3603 and euro 4682 per patient (respectively) and avoid 0.44 and 0.59 relapses per patient in 5 years. Sensitivity analyses showed that the outcome of dominance was only sensitive to estimates about unit costs of hospital/institutionalization, potential risk, and to the reduction in symptoms by use of atypicals. CONCLUSION: Based on this modeling exercise, it could be expected that LAR may be a cost-effective treatment with limited budget impact in Portugal. However, further studies are required to test the generalizability of the results of the present modeling study to the larger population of Portugal.

[Pharmaco-economic evaluation of mandatory HIV-screening in pregnancy; a cost-efficacy analysis in Amsterdam]. / Farmaco-economische evaluatie van universele HIV-screening in de zwangerschap; een kosteneffectiviteitsanalyse voor Amsterdam.

OBJECTIVE: To estimate the cost effectiveness of universal screening for HIV of pregnant women in Amsterdam. DESIGN: Pharmaco-economic model calculation. METHOD: An estimate was made of the minimal and maximal prevalences of undiagnosed HIV infection during pregnancy for the whole of Amsterdam, based on epidemiological data from observation among pregnant women in two Amsterdam hospitals and one obstetrical practice. The calculation was based on universal screening with an ELISA test. The interventions after screening comprised pharmacotherapy during pregnancy, delivery by caesarean section and breast-milk substitution. The issues of pharmaco-economic analysis were whether or not costs were reduced and net costs per year of life gained; the question was also studied at what lifetime costs of care for HIV infected children the net costs would be nil (costs equal benefits). RESULTS: Universal HIV screening in Amsterdam required a total investment of about Dfl 300,000.-per annum. In many of the analysed options for HIV screening the financial profits exceeded the investment. Variation of assumptions showed that the net costs of HIV screening under all conditions investigated would remain below Dfl 1,200.-per life year gained. CONCLUSION: Universal HIV screening of pregnant women in Amsterdam showed a favourable cost effectiveness. The calculations indicated a possibility of reducing costs.