Budget Impact of Dabrafenib and Trametinib in Combination as Adjuvant Treatment of BRAF V600E/K Mutation-Positive Melanoma from a U.S. Commercial Payer Perspective.

BACKGROUND: Before the approval of dabrafenib and trametinib in combination, there were no approved therapies in the adjuvant setting that target the RAS/RAF/MEK/ERK pathway. OBJECTIVE: To evaluate the budget impact of dabrafenib and trametinib in combination for adjuvant treatment of patients with BRAF V600 mutation-positive resected Stage IIIA, IIIB, or IIIC melanoma from a U.S. commercial payer perspective using data from the COMBI-AD trial, as well as other sources. METHODS: The budget impact of dabrafenib and trametinib in combination for patients with BRAF V600E/K mutation-positive, resected Stage IIIA, IIIB, or IIIC melanoma was evaluated from the perspective of a hypothetical population of 1 million members with demographic characteristics consistent with those of a commercially insured U.S. insurance plan (i.e., adults aged less than 65 years) using an economic model developed in Microsoft Excel. The model compared melanoma-related health care costs over a 3-year projection period under 2 scenarios: (1) a reference scenario in which dabrafenib and trametinib are assumed to be unavailable for adjuvant therapy and (2) a new scenario in which the combination is assumed to be available. Treatments potentially displaced by dabrafenib and trametinib were assumed to include observation, high-dose interferon alpha-2b, ipilimumab, and nivolumab. Costs considered in the model include those of adjuvant therapies and treatment of locoregional and distant recurrences. The numbers of patients eligible for treatment with dabrafenib and trametinib were based on data from cancer registries, published sources, and assumptions. Treatment mixes under the reference and new scenarios were based on market research data, clinical expert opinion, and assumptions. Probabilities of recurrence and death were based on data from the COMBI-AD trial and an indirect treatment comparison. Medication costs were based on wholesale acquisition cost prices. Costs of distant recurrence were from a health insurance claims study. RESULTS: In a hypothetical population of 1 million commercially insured members, 48 patients were estimated to become eligible for treatment with dabrafenib and trametinib in combination over the 3-year projection period; in the new scenario, 10 patients were projected to receive such treatment. Cumulative costs of melanoma-related care were estimated to be $6.3 million in the reference scenario and $6.9 million in the new scenario. The budget impact of dabrafenib and trametinib in combination was an increase of $549 thousand overall and 1.5 cents per member per month. CONCLUSIONS: For a hypothetical U.S. commercial health plan of 1 million members, the budget impact of dabrafenib and trametinib in combination as adjuvant treatment for melanoma is likely to be relatively modest and within the range of published estimates for oncology therapies. These results may assist payers in making coverage decisions regarding the use of adjuvant dabrafenib and trametinib in melanoma. DISCLOSURES: Funding for this research was provided to Policy Analysis Inc. (PAI) by Novartis Pharmaceuticals. Stellato, Moynahan, and Delea are employed by PAI. Ndife, Koruth, Mishra, and Gunda are employed by Novartis. Ghate was employed by Novartis at the time of this study and is shareholder in Novartis, Provectus Biopharmaceuticals, and Mannkind Corporation. Gerbasi was employed by PAI at the time of this study and is currently an employee, and stockholder, of Sage Therapeutics. Delea reports grant funding from Merck and research funding from Amgen, Novartis, Sanofi, Seattle Genetics, Takeda, Jazz, EMD Serono, and 21st Century Oncology, unrelated to this work.

[Bisphosphonate use and related pharmaceutical issues II]. / A biszfoszfonátok alkalmazásának gyakorlata és aktuális gyógyszerészeti vonatkozásai II.

UNLABELLED: Bisphosphonates have basic role in decreasing progression of malignant bone processes as well as in the prevention and therapy of osteoporosis. Use of bisphosphonates is common in Hungary since 20 years. In the past decade their reimbursement has been changed several times, the use of generics decreased the price of bisphosphonates. In this paper we analyze the consumption of prescribed bisphosphonates in Hungary. DATA: Prescription data of the National Health Insurance Fund of Hungary. METHOD: We analysed the prescribed bisphosphonates between 2006-2014. We examined the type and amount of bisphosphonates used by years. After identifying therapy areas of use, we calculated the years of therapy from the DOT data. From this data we estimated the mean bisphosphonate therapy costs and costs falling for the patients. Changes in the reimbursement system regarding these medications was analysed. RESULTS: Bisphosphonate years of therapy was decreasing in osteoporosis over the 9 years examined. In oncology bisphosphonate use shows stability in drug consumption. In both therapeutic areas the proportion in therapy choice of specific bisphosphonates has changed. Bisphosphonate reimbursement costs paid by the Hungarian reimbursement system was approx. 8 billion HUF in osteoporosis and 4,7 billion HUF in oncology in 2006. Changes of the reimbursement strategy, the compulsory generic use and decreasing consumption in osteoporosis has significantly reduced the overall costs by 2014. CONCLUSION: According to our results bisphpsphonate use in oncology is moderate in Hungary, a decreasing consumption can be detected in osteoporosis, that is still expected to decrease. The use of generics reduced bisphosphonate therapy costs and also overall health care costs. In osteoporosis patients cost have substantially lowered.

Real-world dosing and drug costs with everolimus or axitinib as second targeted therapies for advanced renal cell carcinoma: a retrospective chart review in the US.

OBJECTIVE: To describe dosing patterns and to compare the drug costs per month spent in progression-free survival (PFS) among patients with advanced renal cell carcinoma (aRCC) treated with everolimus or axitinib following a first tyrosine kinase inhibitor (TKI). METHODS: A medical record retrospective review was conducted among medical oncologists and hematologists/oncologists in the US. Patient eligibility criteria included: (1) age ≥18 years; (2) discontinuation of first TKI (sunitinib, sorafenib, or pazopanib) for medical reasons; (3) initiation of axitinib or everolimus as a second targeted therapy during February 2012-January 2013. Real-world dosing patterns were summarized. Dose-specific drug costs (as of October 2014) were based on wholesale acquisition costs from RED BOOK Online. PFS was compared between everolimus and axitinib using a multivariable Cox proportion hazards model. Everolimus and axitinib drug costs per month of PFS were compared using multivariable gamma regression models. RESULTS: A total of 325 patients received everolimus and 127 patients received axitinib as second targeted therapy. Higher proportions of patients treated with axitinib vs everolimus started on a higher than label-recommended starting dose (14% vs 2%) or experienced dose escalation (11% vs 1%) on second targeted therapy. The PFS did not differ significantly between patients receiving everolimus or axitinib (adjusted hazard ratio (HR) = 1.16; 95% confidence interval [CI] = 0.73-1.82). After baseline characteristics adjustment, axitinib was associated with 17% ($1830) higher drug costs per month of PFS compared to everolimus ($12,467 vs $10,637; p < 0.001). LIMITATIONS: Retrospective observational study design and only drug acquisition costs considered in drug costs estimates. CONCLUSIONS: Patients with aRCC receiving axitinib as second targeted therapy were more likely to initiate at a higher than label-recommended dose and were more likely to dose escalate than patients receiving everolimus. With similar observed durations of PFS, drug costs were significantly higher-by 17% per month of PFS-with axitinib than with everolimus.

A pharmacoeconomic analysis of sertindole in the treatment of schizophrenia in Sweden.

BACKGROUND: Atypical antipsychotics have similar clinical efficacy in the treatment of schizophrenia; variability in their tolerability represents the discerning factor in treatment choices. Sertindole has a relatively good tolerability profile that favours long-term patient adherence and, therefore, is associated with lower rates of relapse and rehospitalization. AIM: A model was developed to compare the cost-effectiveness of a 5-year treatment strategy starting with sertindole versus olanzapine, risperidone, aripiprazole or the typical antipsychotic agent, haloperidol. METHODS: The model was based on published trials and local clinical practice, and considered costs from the perspective of the Swedish National Health Insurance Board. RESULTS: All atypical agents were clinically superior and more cost-effective than haloperidol with a cost per quality-adjusted life year gained of approximately 490,000 Swedish kroner. Sertindole was associated with the lowest direct and indirect medical costs, driven by its tolerability profile. CONCLUSIONS: Sertindole represents a useful alternative to the current treatment options available in Sweden. CLINICAL IMPLICATIONS: The relatively good tolerability profile of sertindole translates into lower costs of schizophrenia management, primarily driven by substantially lower direct and indirect costs. Sertindole appears to be a clinically and cost-effective alternative in the management of patients with schizophrenia in Sweden.

[Fixed drug combinations in hypertension: a budget impact analysis for the Spanish Health System on the marketing of a fixed combination of olmesartan/amlodipine]. / Las combinaciones fijas en hipertensión: análisis de impacto presupuestario para el Sistema Nacional de Salud Español de la comercialización de la combinación fija de olmesartan/amlodipino.

OBJECTIVE: To carry out a budget impact analysis (BIA) of olmesartan/amlodipine (20/5, 40/5 and 40/10mg) marketed as a fixed combination (FC) in its approved indication for the National Health System (NHS). DESIG: We developed a decision tree model in order to estimate usual hypertension treatment algorithm in Spanish clinical practice. SETTINGS: The BIA has been developed from the perspective of the NHS for a period of 3 years (years 2010-2012). PARTICIPANTS: Spanish hypertensive population ≥ 35 years old. INTERVENTIONS: Introduction into the market of a fixed combination (FC) olmesartan/amlodipine in Spain. PRIMARY MEASURES: Expected costs to be assumed by the Spanish NHS (RRP-VAT) for hypertensive population able to be treated with the FC versus currently assumed costs by the NHS with free combination olmesartan and amlodipine. RESULTS: Estimated pharmaceutical costs in hypertensive population treated with olmesartan and amlodipine (2 pills) would be €25.2M (1(st) year), €26.4M (2011), €27.6M (2012), with a total 3-year period of €79.2M. According to patient tree model, the population able to be treated with FC would be 71,283 patients (2010), with a growth rate of 4.8% in the successive years, which supposes an annual cost of €21.2M (2010), €21.8M (2011) and €22.4M (2012), with a total 3-year period of €65.4M. The BIA shows savings of €13.8M in a total 3-year period. CONCLUSION: The BIA of FC olmesartan/amlodipine could generate net savings of €13.8M for the NHS in the period ranging from years 2010 to 2012.

Cost-effectiveness of oral clodronate compared with oral ibandronate, intravenous zoledronate or intravenous pamidronate in breast cancer patients.

This study aimed to identify the effects of different bisphosphonates in reducing skeletal-related events, and to determine whether there are any differences in their cost-effectiveness, taking into account their efficacy, safety profile and administration routes. A systematic literature search of databases, such as PubMed and the Cochrane Controlled Trials Register, supplemented by the latest congress abstracts from meetings of the European Hematology Association and the American Society of Clinical Oncology was conducted up to November 2006. Important references in reviews published by peer-reviewed journals were also taken into consideration. Our base-case cost-effectiveness analysis for Germany and the UK showed cost savings for oral clodronate therapy compared with other bisphosphonate therapies. In Germany, costs per patient of treatment with oral clodronate were euro1092.38, euro2360.40 and euro2500.29 less than with oral ibandronate, intravenous pamidronate and intravenous zoledronate, respectively. The UK results were similar, the costs per patient of treatment with oral clodronate being euro841.79, euro2989.99 and euro3669.19 less than with oral ibandronate, intravenous pamidronate and intravenous zoledronate, respectively.

Adjunctive treatment with moxonidine versus nitrendipine for hypertensive patients with advanced renal failure: a cost-effectiveness analysis.

BACKGROUND: Systemic hypertension often accompanies chronic renal failure and can accelerate its progression to end-stage renal disease (ESRD). Adjunctive moxonidine appeared to have benefits versus adjunctive nitrendipine, in a randomised double-blind six-month trial in hypertensive patients with advanced renal failure. To understand the longer term effects and costs of moxonidine, a decision analytic model was developed and a cost-effectiveness analysis performed. METHODS: A Markov model was used to extrapolate results from the trial over three years. All patients started in a non-ESRD state. After each cycle, patients with a glomerular filtration rate below 15 ml/min had progressed to an ESRD state. The cost-effectiveness analysis was based on the Dutch healthcare perspective. The main outcome measure was incremental cost per life-year gained. The percentage of patients progressing to ESRD and cumulative costs were also compared after three years. In the base case analysis, all patients with ESRD received dialysis. RESULTS: The model predicted that after three years, 38.9% (95%CI 31.8-45.8) of patients treated with nitrendipine progressed to ESRD compared to 7.5% (95%CI 3.5-12.7) of patients treated with moxonidine. Treatment with standard antihypertensive therapy and adjunctive moxonidine was predicted to reduce the number of ESRD cases by 81% over three years compared to adjunctive nitrendipine. The cumulative costs per patient were significantly lower in the moxonidine group 9,858 euro (95% CI 5,501-16,174) than in the nitrendipine group 37,472 euro (95% CI 27,957-49,478). The model showed moxonidine to be dominant compared to nitrendipine, increasing life-years lived by 0.044 (95%CI 0.020-0.070) years and at a cost-saving of 27,615 euro (95%CI 16,894-39,583) per patient. Probabilistic analyses confirmed that the moxonidine strategy was dominant over nitrendipine in over 98.9% of cases. The cumulative 3-year costs and LYL continued to favour the moxonidine strategy in all sensitivity analyses performed. CONCLUSION: Treatment with standard antihypertensive therapy and adjunctive moxonidine in hypertensive patients with advanced renal failure was predicted to reduce the number of new ESRD cases over three years compared to adjunctive nitrendipine. The model showed that adjunctive moxonidine could increase life-years lived and provide long term cost savings.

A cost analysis of topical drug regimens for dermatophyte infections.

OBJECTIVE: To examine the extra cost of using higher-priced drugs as initial therapy for dermatophyte infections, because the many available effective drugs vary considerably in cost. DESIGN: Cost analysis from the purchaser's perspective, comparing two prototypical regimens to treat tinea pedis: one in which all patients initially receive a lower-priced drug and those with unresponsive infections receive a higher-priced drug at a follow-up office visit, and one in which all patients receive the higher-priced drug from the outset. The reference drug was miconazole, an imidazole available without a prescription, for which reported overall efficacy rates are 70% to 100%. MAIN OUTCOME MEASURES: The threshold efficacy rate (the efficacy rate of miconazole below which it is always less expensive to use a specific higher-priced drug first) and the extra cost (of beginning therapy with a higher-priced drug). RESULTS: Assuming the Medicare-approved charge for a follow-up visit ($21.98), it is less expensive to begin therapy with a prescription drug only if the efficacy rate of miconazole is less than 55%; this threshold efficacy rate varied from 26% (for a $0 total cost of the follow-up visit) to 79% (for an $89 total cost of the follow-up visit). If the efficacy rate of miconazole is 70%, the extra cost per patient for all patients to receive the least expensive prescription antifungal drug instead of miconazole first was $15.23 and $8.64 if total visit costs were $0 and $21.98; miconazole remained the less expensive alternative as long as the total cost of the follow-up visit was less than $50.76. CONCLUSION: For reported efficacy rates and standard costs of a follow-up office visit, using miconazole first and then treating only those patients with unresponsive infections with a higher-priced prescription drug is less expensive than treating all patients with the higher-priced drug.