Pharmacoeconomics: theory and practice
№1, 2016, Vol.4

Alferova I.P., Velednitskiy V.B., Vinoglyadova S.V., Voronin S.V., Golihina T.A., Goroshko L.V., Davydova A.N., Zhukova T.P., Irinina N.A., Kapustina N.K., Kuzin A.V., Kulikov A.Y., Lukina N.V., Mardanova A.K., Maryashina T.M., Matulevich S.A., Mihalchuk V.V., Nelyubova Z.G., Nikonov A.M., Pushkina M.A., Rybchenko Y.V., Sahar O.V., Teunaeva M.M., Hramihina S.S., Chesnokova M.A., Shelkova E.V., Erbis G.A., Yudintseva T.V., Yagudina R.I. 881

Phenylketonuria is a hereditary disease associated with a metabolic disorder of amino acids in the organism, the prevalence of which in the Russian Federation is 1:10000. Currently, the main treatment of phenylketonuria is diet therapy with specialized health food (a mixture of amino acids without phenylalanine). This research presents the results of a comparison of diet therapy with medicinal mixtures of MDmil PKU line taken from the first month of life of a child compared to food of other producers, taken in later periods. Efficiency analysis is based on data provided by the major regional genetics specialists from 24 regions of the Russian Federation on treatment of 1088 children suffering from phenylketonuria. Cost analysis of treatment of patients with PKU until their majority reveals least expensive diet therapy initiated from the first month of life with specialized health food of MDmil PKU line compared with diet, started in later periods with specialized products of different manufacturers. During the “cost-effectiveness” analysis and the “cost-utility”analysis indicators of CER and CUR are identified showing that when used from the first month of life diet therapy with MDmil PKU line compared with diet, started in later periods with various manufacturers, it is easy to determine treatment of the first group of children as dominant. Budget impact analysis shows that diet therapy with specialized health food of MDmil PKU line in treatment of phenylketonuria can achieve cost savings of 34% to 38% depending on periods of commencement of the diet.

Kulikov A.Y., Larionova V.B., Snegovoy A.V., Ugrekhelidze D.T. 939

As part of this work a pharmacoeconomic study of prophylaxis for febrile neutropenia with granulocyte colony-stimulating factor drugs was carried out. Four prevention schemes of G-CSFs were compared: lipegfilgrastim, pegfilgrastim, filgrastim, lenograstim. As a result, it was found that prophylaxis with lipegfilgrastim is characterized by the lowest “cost-effectiveness” ratio (217,352 rubles) as compared to prophylaxis with pegfilgrastim (342,748 rub.), filgrastim (302,077 rub. for 11 days of prophylaxis), lenograstim (788,582 rub. for 11 days of prophylaxis) by the end of the 1st year of prophylaxis. In the context of budget impact analysis, the least costly scheme was prophylaxis with lipegfilgrastim (211,484 rubles) by the end of the 1st year when calculating per 1 patient. Costs in pegfilgrastim group resulted in 314,986 rubles, in filgrastim group (11 days of treatment) – 264,620 rubles, in lenograstim group (11 days of treatment) – 690,798 rubles. In the context of pharmacoeconomic analysis it is preferable to use lipegfilgrastim for prophylaxis of febrile neutropenia as compared to other G-CSFs (pegfilgrastim, filgrastim, lenograstim), as it allows to increase the number of patients who responded to prophylaxis of febrile neutropenia while reducing costs as compared to other granulocyte colonystimulating factor drugs.

Kulikov A.Y., Tishchenko D.G. 887

This paper represents the results of pharmacoeconomic study of the drug pomalidomide use in treatment of patients with relapsed or refractory multiple myeloma (MM) with more than 50% reduction in M protein, who have received at least two lines of therapy comprising lenalidomide and bortezomib. Lenalidomide and bortezomib were used as comparative treatment options in the study. The pharmacoeconomic study was carried out using the methods for analysis of efficiency, cost, cost-effectiveness, sensitivity and impact on the budget under frame of the medicinal assistance program for people suffering from hemophilia, cystic fibrosis, pituitary dwarfism, Gaucher’s disease, formation of malignant lymphoid haematogenic and related tissues, multiple sclerosis, as well as organ and/or tissue transplants (hereinafter referred to as the Seven Nosologies (VZN) Program). The time horizon of the «impact on the budget» analysis for the “Seven Nosologies” program was consisted of 4 years (2015–2018). The pharmacoeconomic analysis showed that pomalidomide can be recommended for inclusion in the “Seven Nosologies” federal program within the existing budget. From the perspective of the cost-effectiveness analysis, pomalidomide is the dominant option, since the use of pomalidomide in the MM treatment has a significant advantage over lenalidomide and bortezomib therapy in terms of «cost of the average time to disease progression» and «value of survival time». In other words, pomalidomide therapy has the lowest cost of achieved efficiency unit. Analysis of the impact on the budget in case of pomalidomide (Imnovid) inclusion into the pattern of government procurement as part of the “Seven Nosologies” program for the target period (2016–2018) showed that pomalidomide inclusion will not lead to increase the program budget.

Babiy V.V., Kulikov A.Y., Shestakova I.V. 869

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.

Kulikov A.Y., Pochuprina A.A. 861

Pharmacoeconomic evaluation of patients with BRAF mutation-positive melanoma treatment with dabrafenib and vemurafenib was conducted in the present study. When analyzing the costs required per one year of the therapy with the drugs being compared, it was established that treatment with dabrafenib was 28% less expensive in comparison with vemurafenib, and the differences in the cost per patient per year was 1,633,622 RUB. The budget impact analysis has shown that dabrafenib comparing to vemurafenib treatment to may reduce budget costs by 1,268,108 RUB per patient within first one year. The results based on data from previous clinical studies have shown that treatment with dabrafenib reduces costs by 35% as compared to the therapy with vemurafenib. Analysis demonstrated that throughout the projected cohort of patients (1245 patients), requiring BRAF-kinase inhibitors treatment, dabrafenib treatment allows to treat additional 680 patients in comparison with vemurafenib within the period before the beginning of progression. Therefore, dabrafenib therapy is preferred treatment option for patients with BRAF mutation-positive advanced and unresectable melanoma in Russian Federation.

Kulikov A.Y., Novikov D.E. 1150

Objective: to assess pharmacoeconomic aspects of treatment substitution of metformin immediate release (IR) form for metformin extended release (XR) form in diabetes mellitus (DM) type 2 treatment in Russian Federation healthcare system.
Methods: retrospective modelling performed according to standardized pharmacoeconomic methods such as: “cost-effectiveness analysis”, “budget impact analysis”, “sensitivity analysis”. Markov model with 20-years time horizon was used to forecast compared therapy methods long-term impact on “cost-effectiveness” results in terms of QALY, direct and indirect costs. Analyzed competitors: Glucophage Long (metformin extended release (XR) form) and three generic metformin immediate release (IR) forms which are in the lead of consumption on Russian market (Siofor, Metformin-Richter, Formetin).
Results: the results of effectiveness analysis QALY-scores were 5.2925 and 4.6479 (20-years horizon with 3% discount rate) for metformin XR and IR forms respectively. While total expenditures are 3169258.07 b for Glucophage Long (XR form) therapy and 3 422 420.90 b, 3 426 951.18 b and 3 439 108.79 b for Formetin, Metformin-Richter and Siofor respectively.
Conclusion: metformin XR using improves glycemic control in comparison to metformin IR, which mediately (according to modelling results) decrease risk of DM complications and, in hence, decrease expenditures. Therefore and due to the most favorable tolerance, Glucophage Long therapy demonstrates the minimal total expenditures with the maximum QALY-scores.

Arinina E.E., Kulikov A.Y., Tolordava G.A. 874

Blockade of renin-angiotensin system (RAS) remains one of the most main strategies in treatment of arterial hypertension (AH), and drugs blocking this system, mainly angiotensin-converting-enzyme inhibitor (ACEI) and blockers of receptors to angiotensin II, are the main classes of antihypertensive drugs. The presence of different clinical effectiveness of drugs in these groups, as well as different frequencies of occurrence of undesirable cardiovascular events, side effects and formed the basis of pharmacoeconomic (PE) studies. According to the conducted cost-effectiveness analysis, the treatment regimen using Monopril is characterized by lowest cost and the lowest coefficient of cost-effectiveness ratio in the treatment of patients with AH. The results of the budget impact analysis suggest that therapy with Monopril leads to budget savings. The results of the sensitivity analysis demonstrated the adequacy of the performed pharmacoeconomic analysis and the stability of the obtained data – during the change of the cost factors in the range of ± 97% the therapy with the drug Monopril maintained its advantage expressed by the results of the cost-effectiveness analysis. Сost-effectiveness analysis and budget impact analysis were used in this study. The indirect comparison of two antihypertensive drugs was performed: ACEI (fosinopril, ramipril, lisinopril, perindopril) and ARB II (valsartan, losartan, telmisartan, candesartan). Both groups of drugs are not only one of the main classes of antihypertensive drugs, which can be prescribed to all patients with AH, but also have priority indications, such as diabetes mellitus, metabolic syndrome etc. Results of costs analysis show that fosinopril treatment scheme is characterized with total costs - 22 751 rub., with the lowest cost-effectiveness ratio – 285, during the treatment of AH and budget economy from 5 048 rub. to 46 805 rub. per 1 person per year compared with–ramipril, lisinopril, perindopril, valsartan, losartan, telmisartan, candesartan.

Kulikov A.Y., Petrovskiy A.V., Rybchenko Y.V., Skripnik A.R. 886

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.

Kulikov A.Y. 905

Introduction. On average, about 520,000 cases of acute coronary syndrome (ACS) are registered annually in Russia, and 41,136 patients in 2013 underwent percutaneous coronary intervention (PCI). Every year Russia loses from 100,000 to 120,000 years of life of the working-age population, predominantly male, which leads to a significant loss of the working-age population of the country and presents a significant threat to social and economic welfare of society [8]. The use of more effective antiplatelet therapy in ACS patients can improve outcomes, thus contributing to the reduction in cardiovascular mortality and improving long-term prognosis.
Objectives. The aim of this study was to perform a comparative pharmacoeconomic analysis of ticagrelor + ASA and clopidogrel + ASA therapy in patients with ACS undergoing PCI in the context of the Russian health system.
Results. Analysis of effectiveness revealed that effectiveness of ticagrelor + ASA treatment regimen was higher. Cost-effectiveness analysis showed that ticagrelor + ASA was a dominant therapy considering average prices in Russia by the results of tenders, as well as ticagrelor price planned for registration in the Essential Medicines List and prices for clopidogrel registered in the Essential Medicines List. According to the results of budget impact analysis, the use of ticagrelor + ASA regimen leads to money saving considering average prices in the Russian Federation by the results of tenders, as well as ticagrelor price planned for registration in the Essential Medicines List and price of Clopidogrel registered in the Essential Medicines List.
Conclusion. Therapy of acute coronary syndrome patients managed with PCI with combination of ticagrelor and ASA is economically preferable in comparison with therapy with combination of clopidogrel and ASA