Kulikov Andrey Yurievich

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.

According to the World Health Organization, breast cancer is the most common form of cancer in women worldwide. The steady increase in the prevalence of breast cancer, followed by an increase in the state budget expenditures on drug supply for this category of patients, determines the relevance of pharmacoeconomic evaluation of treatment of HER2-positive breast cancer using a combination of lapatinib and capecitabine and trastuzumab emtansine monotherapy. A subgroup analysis of the therapeutic outcomes in patients with HER2+ breast cancer conducted by the EMILIA study failed to find a statistically significant difference in median overall survival in patients receiving either trastuzumab emtansine or a combination of lapatinib and capecitabine as second-line treatment, or in patients with non-visceral metastases. Analysis of overall survival of the entire population of patients in the EMILIA study revealed that trastuzumab emtansine is more effective than a combination of lapatinib and capecitabine. Despite this, NICE does not recommend treatment with trastuzumab emtansine due to high cost of treatment. The EMILIA study results were used as a basis for pharmacoeconomic models for HER2+ breast cancer therapy, using such methods of pharmacoeconomic analysis as budget impact analysis, cost-effectiveness analysis, and costminimization analysis for these subgroups of patients. Result of budget impact analysis revealed that the use of the lapatinib and capecitabine combination can reduce health system expenditures by 3,985,271 rubles per patient per year or by 5,851,484 rubles over three years per one patient, which allows treating 4 additional patients given the fixed budget. Cost-effectiveness ratio of lapatinib + capecitabine equals to 869,705 rubles and 3,461,960 rubles with LYG and QALY as efficacy endpoints, respectively, which identifies this therapy as cost-effective in pharmacoeconomic terms. Cost-minimization analysis of lapatinib+capecitabine patient groups in the second-line treatment, and a group of patients with non-visceral metastases showed that the use of this treatment may reduce costs by 78% in comparison with trastuzumab emtansine.

The goals of this study was: 1. to evaluate the superior regimen of antiviral drug treatment of chronic hepatitis C (daclatasvir + asunaprevir (a combination of the medicinal products) versus perginterferon alfa + ribavirin or peginterferon alfa + ribavirin + simeprevir or paritaprevir + ritonavir + ombitasvir + dasabuvir) in treatment-naive and treatment-experienced patients (HCV genotype 1b) without liver cirrhosis and with liver cirrhosis based on comparison of cost, effectiveness and safety; 2. To define, using «budget impact» analysis, economic outcomes of including daclatasvir + asunaprevir in current practice of HCV treatment This analysis was performed using two scenarios of the adjusted model “The MONARCH Cost-effectiveness Model”. «Budget impact» analysis was conducted using adapted model «ALLY: Daklinza® (Daclatasvir) Budget Impact Model». The study demonstrated that the first study hypothesis was correct: the combination of the medicinal products for treatment of HCV-infection (HCV genotype 1) daclatasvir + asunaprevir was found to have advantages over the combinations peginterferon alfa + ribavirin, peginterferon alfa + ribavirin + simeprevir and dasabuvir, ombitasvir + paritaprevir + ritonavir in respect of the cost-effectiveness ratio. Furthermore, results of «budget impact» analysis confirmed the second study hypothesis – introduction of DCV + ASV in current practice of HCV treatment will lead to decreasing of complication treatment costs.

Breast cancer is a malignant neoplasm that develops from the epithelial cells of ducts and lobules of the glandular parenchyma, which according to the World Health Organization (WHO) is the most common form of cancer among women (16% of all cases) in the world. In 2014, in Kaluga, Lipetsk, Smolensk and Tula regions the mortality from breast cancer reached 3.2%, 3.1%, 4% and 4.7%, respectively. One of the aggressive forms of breast cancer is a HER2positive (HER2+) subtype (14 to 20% of all subtypes), which is treated with targeted therapy. The appearance of trastuzumab for subcutaneous administration has a number of advantages compared to the intravenous formulation. A pharmacoeconomic analysis of treatment of HER2+ breast cancer was performed by comparing trastuzumab in two formulations in Kaluga, Lipetsk, Smolensk and Tula regions. According to the “cost minimization” analysis in the analyzed regions, the use of trastuzumab for subcutaneous administration compared to intravenous administration saves from 29.7 to 34% of funds. The forecasted budget savings as a result of the budget impact analysis for 10 patients is 8,068,360 rubles in Kaluga region, 7,047,430 rubles in Lipetsk region, 6,534,750 rubles in Smolensk region, and 7,188,980 rubles in Tula region for the treatment course with trastuzumab in subcutaneous formulation as compared to the intravenous formulation. The results showed that the use of trastuzumab therapy in the subcutaneous formulation allows treatment of 4 additional patients with HER2+ breast cancer in Smolensk region, and 5 patients in Kaluga, Lipetsk and Tula regions within a fixed budget.

This paper is devoted to assessment of economic burden of excessive alcohol consumption in Russian Federation. In the course of analysis, we gathered data about direct costs of treatment of conditions, directly or indirectly caused by excessive alcohol consumption, and indirect costs. A total burden of excessive alcohol consumption is more than 547 billion rubles, which makes up to 0,68% of Russia’s GDP for the year 2015. Since 2010 the burden has decreased by nearly 100 billion rubles, and the decrease of burden in relative values from 1,98% to 0,68% of GDP, which gives the evidence of the effectiveness of the government policy in the sphere of alcohol consumption control.

A pharmacoeconomic study of cerebrovascular accident treatment with Cellex was conducted at the background of routine clinical practices in comparison with routine clinical practices only. It was found that in the first case the therapy is dominant in comparison with the second one as it shows better therapeutic effectiveness and is characterized by a lower cost-effectiveness ratio. It was also defined that transfer of one patient from routine clinical practices to Cellex treatment at the background of routine clinical practices is supported with the economy of 7 313 rubles.

During the current study, a pharmacoeconomic assessment of liver failure prevention after using Remaxol® (succinic acid, N-methylglucamine, inosine, methionine, nicotinamide – hereinafter SMIMN) vs. ademetionine was performed in patients with extensive liver resection. As a primary efficacy endpoint, a number of patients needed to treat (NNT) to reach a Child-Pugh Grade A liver functional state was used while analyzing therapeutic efficacy. In the clinical study, Khoronenko et al. demonstrated, that efficacy of SMIMN was higher than ademetionine in restoring liver functional state. On Day 5 and 12 after liver resection cost-effectiveness ratio measured in SMIMN vs. ademetionine groups was 39,624 vs. 96,634 Rub and 34,661 vs. 55,236 Rub, respectively, favoring conclusion that use of SMIMN exhibiting higher efficacy is a dominant approach for preventing acute liver failure (ALF) after extensive liver resection. Budget Impact Analysis revealed that budget savings after treatment with SMIMN vs. ademetionine were 11,831,861 Rub per 1,083 patients, and within a fixed budget, it allowed additionally to treat up to 427 patients

The treatment of multiple sclerosis (MS) is a formidable healthcare challenge the world over. Because MS is a progressive chronic disease, patients living with this diagnosis require treatment for life. The high prevalence of the disease among young people significantly affects patients’ quality of life and exacerbates the socioeconomic burden of the disease. Glatiramer acetate (Copaxone) is a synthetic analogue of the myelin protein that can influence MS pathogenesis with its immunomodulatory and neuroprotective effect. Copaxone has been continuously, safely used in clinical practice for more than 20 years. In terms of tolerance of Copaxone, the main challenge has been the adverse injection reactions associated with daily subcutaneous injection of a 20 mg/mL dose of the drug. To address this, a new pharmaceutical form was developed – Copaxone 40 mg/mL, which requires subcutaneous injection only three times a week. Both dosage regimens have comparable clinical efficacy, but differ in tolerance. Use of Copaxone 40 versus Copaxone 20 was associated with 50% fewer adverse injection reactions [11]. This suggested a need to conduct pharmacoeconomic research with the goal of producing a pharmacoeconomic assessment of Copaxone 40 versus Copaxone 20. The analysis that was conducted using the “cost minimization” analysis determined that the Copaxone 40 treatment method had lower associated costs than did the Copaxone 20 treatment method. The results of a budget impact analysis indicated that, if all patients in the RF [Russian Federation] currently receiving Copaxone 20 were to switch to therapy using the drug Copaxone 40, a cost savings of 812 million roubles would result in lower adverse reaction treatment costs. These savings would be due to the 209 fewer injections per patient per year that would be achieved by prescribing Copaxone 40, and consequently, the lower number of injection reactions.

Melanoma is a malignant tumor that develops from transformed melanocytes, located mainly in the skin. According to Russian statistics, the incidence of melanoma in 2014 was 9,390 new cases [4]. In 2004-2014, melanoma prevalence rate per 100,000 population increased on average by 4.2% per year. High prevalence of melanoma and frequent poor prognosis necessitate search of innovative treatment methods and use of high-tech drugs.

Melanoma is a malignant tumor that develops from transformed melanocytes, located mainly in the skin. According to Russian statistics, the incidence of melanoma in 2014 was 9,390 new cases. In 2004-2014, melanoma prevalence rate per 100,000 population increased on average by 4.2% per year. High prevalence of melanoma and frequent poor prognosis necessitate search of innovative treatment methods and use of high-tech drugs. The unmet need for oncology therapies is substantial. The introduction of innovative, highcost treatments, coupled with mounting budgetary pressures, will necessitate value trade-offs across cancer types. Defining value will be critical to informing decision-making. The purpose of this study was to perform relative value analysis (RVA) of the ipilimumab use in patients with metastatic melanoma among the entire group of oncology products selected for comparison. Relative value analysis (RVA) can be used to benchmark the clinical and economic value delivered by one product versus others in a broad therapeutic class, using acceptable statistical methods applied to clinical and economic measures. These are naive comparisons with no adjustment for differences in trial characteristics or patient populations. The analysis could not be consider as a substiture for ITC/NMA or more sophisticaled cost effectiveness modeling.

Analysis of costs of using lanreotide in patients with GEP-NETs grade 1 or 2 originating from the pancreas(with tumor proliferation index of [Ki-67] <10%) was carried out in this study. Targeted drugs with indications for treatment of pancreatic NETs in the Russian Federation were used for comparison: sunitinib and everolimus. Pharmacoeconomic study was carried out using methods of «cost-effectiveness» analysis including a sensitivity analysis. The study considered the direct costs which included the costs of treatment and the methods of diagnosis according guidelines of RUSSCO (MRI, biopsy and biochemistry blood analysis). As a result, it was found that the average cost of main pharmacotherapy per patient annually using lanreotide is lower than the average cost of treatment using sunitinib or everolimus by 55.2% and 51.9% (845 000 roubles, 1,886,991 roubles and 1758 443 roubles), respectively. This pharmacoeconomic analysis showed that the average total cost of the main drug treatment and medical care services in the treatment of pancreatic NETs using lanreotide is 886,036 roubles. That is lower than the total cost of treatment using sunitinib (1,928,027 roubles) or everolimus ( 1,799,479 roubles) by 54.0% and 50.8%, respectively. When analyzing the ‘cost effectiveness’, progression-free survival (PFS) was chosen as an efficiency criterion. Considering the results of «cost - effectiveness» analysis, the use of lanreotide for the treatment of pancreatic NETs has a significant advantage over therapy using sunitinib or everolimus in terms of median progression-free survival (PFS), CER of lanreotide is lower than CERof sunitinib and CER of everolimus (73 836 rub/month, 160 660 rub/month and 149 957 rub/month respectively) i.e., lanreotide is the option in treatment. This study has limitations due to study design (lareotide open label study) and difference in population between lanreotide study and sunitinib and everolimus studies.

To assess the level of development of pharmacoeconomics in the Russian Federation as a branch of science analysis of pharmacoeconomic and clinical economic studies published in the scientific electronic library “eLIBRARY.RU” (RSCI) for the period from 2005 through 2015 was performed. As a result, it was determined that the number of such studies from year to year is steadily increasing. The leader among the countries who publish their researches on the platform of the scientific electronic library “eLIBRARY. RU” was Russia, the second and the third places were shared by Ukraine and Belarus, respectively. The research was carried out in 52 subjects of the Russian Federation, which is represented by 63 Universities. Leader out of them was the I.M. Sechenov First Moscow State Medical University. It turned out that most pharmacoeconomic and clinical-economic research during the specified time interval was devoted to cardiovascular, pulmonary, oncological and endocrinological diseases. As a result of analysis, it was found that among pharmacoeconomic research methods most commonly used “cost– effectiveness” analysis (45,1%). In addition, on the basis of the analyzed data of Russian science citation index and the total number of published works, the rating of the authors who conducted research in the field of pharmacoeconomics in the country.

Cardiovascular disease (CVD) is the main mortality factor and the main reason of disability of the working-age population both in the Russian Federation and in the world. Due to the state statistical data, 1,878 persons per every 100,000 population died in Russia in 2014. 50.1 % of these deaths have been caused by CVD and more than half of them (52.3 %) have been caused by ischemic heart disease (IHD). The aim of this study was to determine the preferential scheme of medical therapy in perioperative management of cardiac surgery patients with extracorporeal circulation, with IHD or with chronic heart insufficiency (CHI) from the point of view of pharmacoeconomic analysis by comparing ratios between expenses and efficacy, safety and quality of life associated with the use of Neoton (phosphocreatine) in comparison with the control group. Due to the efficacy analysis, the scheme “standard therapy + phophocreatine” is more effective. Cost-effectiveness analysis has shown that the standard therapy + phosphocreatine is a preferable method of treatment in comparison with the standard therapy as it shows better clinical efficacy and lower “costeffectiveness ratio. Results of the budget impact analysis have shown that the use of the standard therapy + phosphocreatine instead of the standard therapy itself in perioperative management of cardiac surgery patients with extracorporeal circulation, with IHD or with CHI has saved money.

Pharmacoeconomic analysis of long-term effects of more widespread use of in vitro fertilization (IVF) in infertility treatment at the regional and federal level from the standpoint of society in the Russian Federation was carried out in this research. The research was performed by means of forecasting of future monetary flows produced by a human born with the aid of in vitro fertilization throughout life. The methods of cost analysis, discounted monetary flows, age shifting and model building were used in the research. The result is that net present value (NPV) of tax payments produced within anticipated life period by the human born with of IVF in the Russian Federation was equal to 822,258 rubles. Return on investments (ROI) was 27%. Net present value (NPV) of GDP produced within the state per one human born with the aid of IVF in the Russian Federation was equal to 34.9 million rubles. Return on investments (ROI) was 985%. Additional carrying out of 24,450 IVF cycles on the basis of OMI CMI (Obligatory Medical Insurance) (the level of 2013) results in increase of total growth of population of the Russian Federation by 22.5%, annual additional carrying out of IVF procedure in the quantity carried out in 2013 will allow to produce additional population growth by 2075 estimated at 319 thousand people in productive age, and 222 thousand people aged up to 20 years.

Psoriatic arthritis (PsA) can develop at any age and often affects the workingage population. In the course of the disease, physical activity of patients decreases, which leads to a drop in performance and absence from work due to treatment. If untreated, this can lead to disability and loss of function of the locomotive system structures. Strategy to combat PsA requires focus on the most effective prevention and control of both the progression of psoriasis, and arthritis associated therewith. It is equally important to minimize the risks associated with major organ toxicity and the development of side effects. In this context, the emergence of drugs for the treatment of psoriasis belonging to a new class of signaling pathways inhibitors seems to be highly relevant both from scientific and practical points of view. In general, biological products, which are antibodies that selectively bind to receptors or proteins on the extracellular membrane, block one biological marker (e.g., TNF-a, IL-17) participating in the immunopathogenesis of psoriasis, thus interrupting further inflammatory cascade of pathological processes leading to the formation of psoriatic efflorescence. Apremilast, which belongs to a new group of drugs - selective inhibitors of signaling pathways - has a fundamentally different mechanism of action. With targeted effect, the drug modulates intracellular signaling, eventually corresponding to the control of the expression of genes mediating key pro- and anti-inflammatory factors (e.g., release of cytokines) in myeloid, lymphoid and other cells involved in the “orchestration” of epidermis inflammation and hyperproliferation. The drug is administered orally, which eliminates additional costs for administering an injection, as is the case with biological drugs. The emergence of a new drug for the treatment of psoriatic arthritis, lack of proper control over the course of the disease, as well as limited healthcare system resources resulted in the pharmacoeconomic assessment of the priority drugs Apremilast compared to ustekinumab, adalimumab and infliximab using cost, cost-effectiveness and budget influence analysis methods. The cost analysis results showed that Apremilast treatment costs for the entire study period - 2 years - are on average 27% lower than the cost of treatment with ustekinumab, adalimumab and infliximab. Otezla treatment is characterized by a lower cost per unit of effectiveness - QALY, when considering the cost for the entire time horizon, as compared to Humira, Stelara and Remicade. Furthermore, the use of Apremilast leads to cost savings if administered for either 2 years or 1 year, in comparison with the alternative regimens.

Iron-deficiency anemia occupies the first place among the most common diseases. Approximately 700 million people worldwide suffer from iron deficiency anemia. In Russia, iron deficiency anemia is diagnosed in 6-30% of the population. The objective of this study was the comparative pharmacoeconomic analysis Cosmofer (Iron III - hydroxide dextran) compared with Venofer (Iron III - hydroxide sucrose complex) in the treatment of iron deficiency anemia for patients with chronic kidney disease. An analysis of the value of the direct costs of patient treatment for 6 months amounted to 17,077 rubles for the treatment of Iron III - hydroxide dextran and 17,792 rubles for the treatment of Iron III - hydroxide sucrose complex. Result of budget impact analysis revealed that the use of the treatment of Iron III - hydroxide dextran as compared with Iron III - hydroxide sucrose complex for one patient, leads to budget savings for 715 rubles. The sensitivity analysis shows that a simultaneous increase the cost of Iron III - hydroxide dextran and decrease the cost of Iron III - hydroxide sucrose complex at 5%, will require additional funding in the amount of 157 ruble.

In conducted pharmacoeconomic study we analyzed treatment of nonresectable stage III-IV melanoma among BRAF-mutated treatment-naïve patients: monotherapy with nivolumab, scheme dabrafenib + trametinib and scheme vemurafenib + cobimetinib. Cost-effectiveness analysis and budgetimpact analysis were based on a modeling approach. Progression free survival (PFS) was used as an effectiveness criteria. Only direct costs of medical help at first-line of antitumor treatment were taken into account. Time horizon was equal to PFS of mentioned treatment schemes. Results of cost-effectiveness analysis showed that the lowest CERPFS was on the monotherapy with nivolumab. In budget-impact analysis using of nivolumab instead of dabrafenib + trametinib and vemurafenib + cobimetinib leaded to decrease of both antitumor treatment costs and total medical costs of first-line treatment of melanoma, resulting in possibility of treatment in 3,3 and 3,6 times more patients within equal budget, respectively (in case of treatment with nivolumab). Obtained results of costeffectiveness analysis were stable to increase of nivolumab price within 1,5-2,0 or to decrease of alternative schemes prices within 1,5-2,0.

The correct treatment of bronchial asthma is a difficult task not only for patients and healthcare professionals but for healthcare authorities as well. The economic burden of the disease is equal to the burden of diabetes mellitus and arterial hypertension. Nearly all indirect costs and not less than a third of direct costs of the treatment of the disease are related to management of exacerbations and poor asthma control. In recent years, there has been a considerable improvement in the treatment of asthma associated with emergence of new medicinal products and delivery devices. Unfortunately, not every patient is able to achieve the optimal disease management level. For this reason, technologies for creation of an effective treatment method for bronchial asthma are undergoing continual improvement nowadays. One of the solutions in this field was the development of inhaler devices producing extrafine aerosol with particle diameter under 2 µm. Such aerosols make it possible for inhalation medicines to reach the small airways, which are the principal site of inflammation in a number of bronchial asthma phenotypes (including bronchial asthma in smokers). The objective of this study was to determine the advantageous medicinal product for bronchial asthma using pharmacoeconomic analysis, on the basis of comparison between costs and effectiveness, safety, and quality of life in treatment with fixed combinations of inhaled glucocorticosteroids and long-acting β2agonists: medicinal products (MP) Foster®, Symbicort® Turbuhaler®, Seretide®, and Seretide® Multidisk. According to the results of the cost-utility analysis, it was determined that the therapy with Foster® is dominant and characterized by the lowest costs with reference to QALY compared to Symbicort® Turbuhaler® and is cost-effective compared to Seretide® and Seretide® Multidisk, on the basis of the obtained values of the incremental cost-utility analysis, which are significantly lower than the willingness-to-pay threshold in the Russian Federation. The budget impact analysis demonstrated that using Foster® for therapy results in budget savings compared to Symbicort® Turbuhaler®, Seretide®, and Seretide® Multidisk when transferring an additional number of patients (21 %) to Foster®.

The objective of this study was to conduct cost-effectiveness analysis and budget impact analysis of antiviral drug treatment of chronic hepatitis C (peginterferon alfa + ribavirin 24 weeks (F0-F4), daclatasvir + sofosbuvir 12 weeks (F0-F3), daclatasvir + sofosbuvir + ribavirin 12 weeks (F4), sofosbuvir + ribavirin 24 weeks (F0-F4)) among treatment-experienced patients (HCV genotype 3). Both analyses were based on the developed pharmacoeconomic model (Markov model). Literature review showed absence of clear effectiveness data on using of peginterferon alfa + ribavirin in the targeted group therefore subsequent pharmacoeconomic analysis for this comparator was aborted. Obtained results showed that daclatasvir + sofosbuvir and daclatasvir + sofosbuvir + ribavirin was dominant in compares with sofosbuvir + ribavirin in the F0-F3 and F4 groups. In budget impact analysis total costs per one patient decreased on 283 623 rubles and 290 168 rubles in case of using daclatasvir + sofosbuvir instead of sofosbuvir + ribavirin among F0-F3 patients and daclatasvir + sofosbuvir + ribavirin instead of sofosbuvir + ribavirin among F4 patients, respectively.

The most dangerous consequences of the global diabetes epidemic are diabetes-related complications. A wide variety of treatment options is currently available for patients with type 2 diabetes mellitus. However, the existing treatments have proven effective for no more than half of diabetic patients who managed to compensate the occurring complications, which is the reason for introducing novel glucose-lowering medicines into practice. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of innovative medicines. Dapagliflozin was the first medicine in this group to be registered on the territory of Russia. Numerous trials have confirmed the efficacy of dapagliflozin at any stage of type 2 diabetes mellitus, both as monotherapy and in combination with metformin, sulfonylureas, dipeptidyl peptidase 4 inhibitors (iDPP-4) and insulin. Thus, the wide range of available glucose-lowering drugs, lack of adequate control over the disease and introduction of novel medicines warrant a new pharmacoeconomic study. The purpose of this study was to perform a pharmacoeconomic evaluation of dapagliflozin as a preferential medicine used to treat patients with type 2 diabetes mellitus, as compared to monotherapy or combined use of medicines of the sulfonylureas, metformin, glyptins, glyflozins and insulin group, by means of a cost analysis, and cost-effectiveness and budget impact analysis. Based on the results of the cost-effectiveness analysis, the dapagliflozin treatment scheme was reported to have the lowest cost of type 2 diabetes therapy to quality adjusted life-year (QALY) ratio compared to therapy regimens involving metformin, sulfonylureas, iDPP-4, basal and bolus insulins. The budget impact analysis demonstrated that treatment using Forxiga would result in budget savings of 31 million rubles over five years, if 1000 patients were to hypothetically switch over from other treatment regimens.