Budget impact analysis is one of the main methods of pharmacoeconomic analysis and obligatory one for pharmacoeconomic assessment during the apply for inclusion in state reimbursement list in the Russian Federation. Results of budget impact analysis being presented in monetary values are the most convincing ones among the pharmacoeconomic values for healthcare decision-makers. The conduct of budget impact analysis includes such stages as choice of effectiveness criteria, costs analysis. During this type of pharmacoeconomic assessment the following factors are taken into account: time horizon, the peculiarities of choice of patients’ models, characteristics of market penetration with health technologies. Budget impact analysis presents wide opportunities for conducted pharmacoeconomic assessment, defining the total economic impact under basic scenario. In the same time budget impact analysis allows to compare the figures of total economic impacts for several technologies, showing the least costly alternatives. If it is necessary using budget impact analysis it is possible to make accurate models describing the budgets of any healthcare programme of ones for treatment of certain nosologies with the function of prognosis and optimization.

Pharmacoeconomic study of different preparations of botulinum toxin type A used for the treatment of cerebral palsy in terms of health of the Russian Federation was conducted. The aim of this study was to determine the most appropriate therapy of cerebral palsy from the pharmacoeconomic point of view. We compared three regimens: botulinum toxin type A - Dysport® in combination with standard therapy, botulinum toxin type A - Botox® in combination with standard therapy and standard therapy without the use of botulinum toxin. It should be noted that centrally acting muscle relaxant (Baclofen) was used in standard therapy, but BTA in this treatment scheme is not used to eliminate unwanted relaxation of the muscles. As a result, it was found that the regimen Dysport®+standard therapy has the lowest cost-effectiveness ratio (11 608 rubles) in comparison with drug therapy Botox®+standard therapy (12 879 rubles) and standard therapy with a centrally acting muscle relaxant without BTA (25 222 rubles) by the end of 2 years of treatment. According to the budget impact analysis at the end of 2 years for 1 patient the scheme Dysport®+standard therapy was the least expensive form of therapy (1 079 500 rubles) in comparison with therapy Botox®+standard therapy (1 159 085 rubles) and standard therapy with a centrally acting muscle relaxant without BTA (1 210 678 rubles).

The market entry of modern recombinant blood coagulation factors VIII have brought the quality and safety of medical help for hemophilia A patients to a higher level. Before 2015 only full-length recombinant blood coagulation factor VIII (INN octocog alfa) was available to patients within the framework of the federal reimbursement program “7 Nosologies”, while in 2015 the first B-domain deleted recombinant factor VIII (INN moroctocog alpha) was included in the program for the first time and also became available to patients. During the analysis of clinical and economic characteristics of these drugs it was found that the cost of treatment with full-length factor VIII is lower than with B-domain deleted factor VIII due to lower risk of inhibitor development and clinically-proven reduction in bleeding frequency on prophylaxis in fulllength recombinant factor VIII, as well as to higher consumption of B-domain deleted factors for effective bleeding prophylaxis. As a consequence, clinically unreasonable patient switching from full-length to B-domain deleted factors requires “7 Nosologies” budget increase comparing to 2014.

In the framework of the presented study, we have performed a pharmacoeconomic analysis of medical care for chronic kidney disease patients who need renal replacement therapy via peritoneal dialysis and hemodialysis. The study results demonstrates that the aggregate costs of peritoneal dialysis therapy, on the average, are lower than those of hemodialysis by 12 % due to the lower costs of treatment of the chronic kidney disease and renal replacement therapy related complications and lower indirect costs due to longer preservation of the capacity for work. Peritoneal dialysis demonstrated higher clinical effectiveness and lower aggregate costs and, as consequence, lower cost-utility ratio, i.e. demonstrated the advantages over hemodialysis.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, which, in the cases of high activity, results in extensive damage to various tissues and organs, as well as promotes early patient disability. Most drugs used for the treatment of SLE are currently prescribed off-label, since this specific indication is not reflected in their prescribing information. At the same time, the advent of belimumab (Benlysta®), an innovative biological product for the treatment of SLE, which represents the most severe connective tissue disorder, provided patients with an access to a highly effective targeted therapy, which specifically impacts one of the main mechanisms of the disease. The innovative and proprietary product, Belimumab, has a relatively high cost, which, as the healthcare budget is restricted, requires that a pharmacoeconomic evaluation be completed of combined use of belimumab with standard of care (SoC) versus SoC alone. The present study showed that the use of belimumab combined with SoC in patients with SLE was, clearly, associated with additional costs compared to SoC alone. However, given low incidence of the condition, the overall increase in costs is unlikely to be significant. On the other hand, it was noted that the high belimumab efficacy resulted in lower direct costs of treating the SLE (cardiovascular, cutaneous, and pulmonary) complications, as well as the costs of hospital care. A comparative analysis has demonstrated that the annual cost of treatment with belimumab was similar to the cost of other genetically engineered biological products, which have already been included into the List of Vital and Essential Drugs used for rheumatic diseases, particularly rheumatoid arthritis. In this view, the use of belimumab, which represents the only targeted drug for SLE, could be considered during the review of policy for subsidised drug provision to patients with this condition.

Currently, in treatment of patients with urothelial transitional cell carcinoma resistant to platinum-based regimen, only Javlor (vinflunine) shows the best evidence when using in second-line chemotherapy scheme. Vinflunine shows the advantage over best supportive care during a randomized Phase III study. The aim of this study is to compare Javlor therapy in combination with the best supportive therapy and the best supportive therapy alone in terms of pharmacoeconomic analysis. Budget impact analysis shows that the treatment of urothelial transitional cell carcinoma with Javlor requires additional expenses. Cost-effectiveness analysis shows that the ICER does not exceed “willingness-to-pay” threshold which means that from the point of view of incremental analysis the therapy in patients with urothelial transitional cell carcinoma using Javlor is cost-effective.

Study purpose: to determine whether canagliflozin is a pharmacoeconomically justified option to be included into therapy for patients with insufficient glycemic control and treated with metformin either as monotherapy administered in the maximum tolerated dose or as a part of a combined therapy with sulfonylurea derivatives taking into account the conditions existing in the Russian Federation.

This document represents the results of validation of pharmacoeconomic model of introduction of medicinal product Ibrutinib into chronic lymphatic leukemia therapy practice within the programme of drug provision for patients with hemophilia, cystic fibrosis, pituitary dwarfism, Gaucher disease, malignant neoplasms of lymphoid, haematopoietic and related tissues, multiple sclerosis, as well as patients after transplantation of organs and/or tissues (hereafter referred to as ‘7 cost-intensive nosologies (7 CIN) programme’). Budget impact analysis demonstrated the possibility to provide all patients requiring Ibrutinib therapy without budget increase using only a part of savings within the programme during a period of 2016 – 2018.

Recent market entry of disease-modifying anti-rheumatic drugs (DMARDs) for patients with rheumatoid arthritis (RA) who had an inadequate response to methotrexate in Russia has secured patient access to highly effective treatment options. Access to effective treatment options are of particular importance for highly prevalent conditions with early function impairment such as RA. Innovative medicines, such as DMARDs, are however typically characterized by high treatment costs and require pharmacoeconomic assessment as part of the decision making process regarding federal reimbursement. In the present study, adaptation of an Italian health economic model was performed with the aim to compare cost-efficacy of subcutaneous abatacept versus adalimumab from the Russian Federation national health care system perspective. Clinical efficacy data as well as patient characteristics were based on the AMPLE trial patient population, which was a direct headto-head comparison of subcutaneous abatacept and adalimumab in RA. The time horizon was set at 2 years, which corresponds with the length of the AMPLE study. Direct medical costs included pharmaceutical costs based on the registered maximum selling prices, cost of adverse event treatment, outpatient and inpatient treatment, and diagnostic and laboratory monitoring costs (Rubles, 2015). Results showed that the total 2-year costs of treating 100 patients were 143,750,205.87 rubles for abatacept compared with 165,749,479.26 rubles for adalimumab, at a total cost-savings of treating an entire cohort with abatacept equal to 21,999,273.38 rubles or 219,992.73 rubles per patient. The cost-effectiveness ratios across all disease activity measures (ACR 20, 50, 70, 90; DAS-28; HAQ-DI; CDAI; SDAI) demonstrated that abatacept compared to adalimumab had a lower cost per health outcome. Therefore, from a pharmacoeconomic point of view, subcutaneous abatacept is most likely a preferable alternative compared with adalimumab for the treatment of RA patients in the Russian Federation.

The study established a superior clinical efficacy in bleeding episodes relieving, and the health care resources saving in contrast with the current treatment regimen, when patients with von Willebrand disease Haemate P treatment receive. Thus, Haemate P shows pharmacoeconomic advantage over current treatment regimen of von Willebrand disease, which includes coagulation factor VIII drugs, as well as Wilate pharmacotherapy, as the most effective and cheap treatment scheme.

In this paper, the main methodological aspects of the willingnessto-pay analysis are highlighted. The values of the willingness-to-pay threshold according to the methodology of the World Health Organization are calculated, the ones of the Russian Federation and the countries of the Group of Twenty and the Commonwealth of Independent States were compared. The international experience of the calculation of willingness-to-pay threshold is covered. Advantages and disadvantages of various methods of calculation of the willingness-to-pay threshold are presented.

Orphan drugs designed for rare disease management is a special group of drugs from the perspective of the pharmacoeconomic analysis being a mandatory part of any proposal for inclusion in the Restrictive lists. Thanks to unique opportunities offered by orphan drugs for rare disease management through acting at the pathogenetic level, these drugs have high social significance. But inherently high cost of these innovative drugs associated with their narrow market limited due to small target population, precludes from using the conventional pharmacoeconomic approach which involves comparison of pharmacoeconomic indicators — results of cost-effectiveness and budget impact analyses — of the innovative drug vs. current medical treatment (or palliative treatment in case of no treatment option available). As such, the authors have investigated the special pharmacoeconomic approach — “precedential” — in case of ruxolitinib in treatment of primary myelofibrosis. This approach implies comparison of the studied drug vs. other orphan and high-cost medicinal products included in the National drug lists. As a result, it has been shown that the pharmacoeconomic indicators of ruxolitinib are not higher than the same of the drugs included in the Essential Drug List .

Budget impact analysis and cost-effectiveness analysis for the therapy of chronic myeloid leukemia (CML) by tyrosine kinase inhibitors were performed by means of a developed analytical model of decisionmaking. This analysis defined potential budget impact of nilotinib as the second-line therapy in the frame of drug reimbursement program for subjects with hemophilia, cystic fibrosis, pituitary dwarfism, Gaucher’s disease, tumors of the lymphoid, haemopoietic and related tissues, multiple sclerosis, as well as for patients subjects to organ (tissue) transplantation (hereafter reimbursement program for high-cost drugs). Budget impact analysis has shown that conversion from imatinib to nilotinib for all subjects with chronic myeloid leukemia (CML) in Russian Federation receiving second-line therapy, based on theoretic consumption, would lead to RUR 1.985 billion increase of the federal budget (compared to imatinib only). Taking into account the actual nilotinib consumption, budget of the Scenario 1 does not exceed the real cumulative amount for chronic myeloid leukemia (CML) treatment in the framework of the reimbursement program for high-cost drugs and regional subsidized drug lists. In addition, it was demonstrated that nilotinib compared to imatinib can be characterized as a strictly preferable drug from the costeffectiveness analysis point of view, as it has a lower cost - effectiveness ratio.

In this article the economic burden of multiple sclerosis in the Republic of Belarus is presented. Analysis is performed using calculation direct and indirect costs.

Chronic myelogenous leukemia (CML) is among the nosologies included in the governmental program for supply of medicines to patients with hemophilia, mucoviscidosis, pituitary dwarfism, Gaucher disease, malignant neoplasms in lymphoid, hematopoietic and related tissues, multiple sclerosis, and also after organ and (or) tissue transplantation. Only one medicine, imatinib, is currently available to CML patients within this program. However, 20% to 35% of CML patients have intolerance or develop resistance to imatinib. Therefore, this patient group should receive treatment with the second-generation tyrosine-kinase inhibitors, in particular dasatinib. Pharmacoeconomic analysis is required for dasatinib to be included in the list of expensive medicinal products. This pharmacoeconomic study investigates the use of dasatinib as a second-line CML therapy, based on «cost-effectiveness» and «budget impact» analysis. The study demonstrated that in terms of cost-effectiveness analysis, dasatinib is a strictly preferred alternative as compared to the high doses of imatinib. Moreover, taking into account consumption rate of dasatinib in the real world settings, it is possible to provide treatment to 100% of patients with resistance and/or intolerance to imatinib without additional funding above the total federal budget for CML treatment in 2014.

The article deals with the results of validation of the pharmacoeconomic model of emtricitabin/ rilpivirine/ tenofovir (Eviplera) inclusion in highly active antiretroviral therapy of HIV/AIDS in the Russian Federation.

The aim of this study was to determine optimal medical technique based on assessing cost and efficacy of treatment of von Willebrand disease using blood clotting factor concentrates (blood clotting factor VIII + von Willebrand factor): Wilate, Haemate P, Immunate. It was determined that in studies on assessing the efficiency of the concentrates more than 95% of patients rated hemostasis excellent/good. However, the studies were based on different scales of efficiency assessment, different vWF:RСo doses and different data for vWD patients (severity of the disease), therefore the efficiency of blood clotting factor concentrates might be not equal. Results of present study with the assumption about equality of groups, that were analyzed in studies on assessing the efficiency of the concentrates (although, studies on Wilate included more severe patients),evidence that prescribing blood clotting factor concentrate Wilate lead to cost savings compared to the older generation products.

In this study, a pharmacoeconomic analysis of chronic lymphocytic leukemia therapy in previously untreated patients was conducted, using treatment regimens obinutuzumab (Gazyva) + chlorambucil and rituximab +chlorambucil. The results of the study showed that though the costs of the first treatment course with obinutuzumab + chlorambucil are significantly higher, this regimen reduces the cumulative cost of subsequent therapy lines in patients with CLL (due to a longer progression-free survival). In the end of the third year of therapy, cumulative costs become relatively similar: with the use of the obinutuzumab + chlorambucil regimen, the cumulative cost per 1 patient/year will be 38,390 rubles higher compared to the rituximab + chlorambucil regimen. At the same time, the obinutuzumab regimen showed a lower cost-effectiveness ratio, i.e. it had an advantage over the alternative technology.

In this study we conducted pharmacoeconomic assessment of the use of canakinumab in patients with cryopyrin-associated periodic syndromes (CAPS) versus the symptomatic treatment alone. Incidence of remission in the treatment group was selected as the efficacy endpoint, and superior efficacy of canakinumab was demonstrated in the treatment group as compared to the symptomatic treatment. Based on cost-effectiveness analysis, it was determined that canakinumab treatment required considerable expenses; however, due to the small number of patients the impact on overall budget will be insignificant. It should also be noted that the treatment with this medicinal product will help reduce the costs of out-patient and policlinic care, in-patient medical care, as well as administration-related and complications management costs.

Pharmacoeconomic study comparing luteinizing hormonereleasing hormone agonists (LHRH-A), used for prostate cancer treatment was conducted. The study included drugs: buserelin, goserelin, triptorelin and leuprorelin. Pharmacoeconomic study included the following methods:cost analysis, cost-effectiveness analysis, cost minimization analysis and budget impact analysis. The time horizon for cost analysis, cost minimization analysis and budget impact analysis amounted to 1 year, whereas for costeffectiveness analysis it was equal to 6 months. Direct costs were taken into account. As a result, it was found that annual costs for the treatment of one patient for each of the considered drugs (buserelin, goserelin, triptorelin and leuprorelin) respectively accounted for 55 169 rubles, 90 130 rubles, 90 133 rubles и 94 599 rubles. Results of the budget impact analysis showed that the annual budget per patient using drug therapy buserelin, goserelin, triptorelin and leuprorelin respectively amounted to 129 545 rubles, 164 506 rubles, 164 509 rubles and 168 974 rubles. Cost minimization analysis demonstrated that under the assumption of equal clinical effectiveness review of medications, annual treatment of one patient using buserelin is characterized with 34 961 rubles compared with goserelin and 39 430 rubles compared with leuprorelin. Cost-effectiveness analysis using the criterion of decreasing the prostatespecific antigen (PSA) level, it was found that buserelin is characterized with the greatest rate of decrease in the PSA value, so it has the smallest value of the cost-effectiveness ratio and, thus, relative to the comparison drugs is strictly preferred drug.