Kulikov Andrey Yurievich

professor of Department of organization of medical provision and pharmacoeconomics, I.M. Sechenov First Moscow State Medical University Moscow,Russia
Babiy V.V., Kulikov A.Y. 1576

The objectives of this study were to determine the most advantageous antiviral therapy option for chronic hepatitis C (CHC) (peginterferon alfa + ribavirin (PegIFN + RBV) 48 weeks (F0–F4), peginterferon alfa + simeprevir + ribavirin (PegIFN + SMV + RBV) 24 weeks (F0–F4), peginterferon alfa + sofosbuvir + ribavirin (PegIFN + SOF + RBV) 12 weeks (F0–F4), dasabuvir + ombitasvir/paritaprevir/ritonavir (Dasabuvir + Ombitasvir/ paritaprevir/ritonavir) 12 weeks (F0–F3) and dasabuvir + ombitasvir/ paritaprevir/ritonavir + ribavirin (Dasabuvir + Ombitasvir/paritaprevir/ritonavir + RBV) 12 weeks (F4)) among treatment-naive and treatment-experienced patients (HCV genotype 1) based on the comparison of cost-effectiveness ratios and economic outcomes (“budget impact” analysis) from implementing the treatment strategy PegIFN-α + SOF + RBV instead of PegIFN-α + RBV, PegIFN-α + SIM + RBV and Dasabuvir + Ombitasvir/paritaprevir/ritonavir. Model-based pharmacoeconomic analysis has been conducted. The costeffectiveness analysis showed that independently of the former treatment experience of CHC (genotype 1) patients the combination PegIFN-α + SOF + RBV was a predominant regimen as compared to PegIFN-α + RBV and PegIFN-α + SMV + RBV. In the groups of patients without cirrhosis and with cirrhosis the highest QALY value was noted for Dasabuvir + Ombitasvir/ paritaprevir/ritonavir and Dasabuvir + Ombitasvir/paritaprevir/ritonavir + RBV combinations, respectively. Also a smaller cost-effectiveness ratio (CER) relative to the two above regimens was noted for PegIFN-α + SOF + RBV. In the group of treatment-naive patients without cirrhosis incremental costeffectiveness ratio (ICER) of Dasabuvir + Ombitasvir/paritaprevir/ritonavir vs PegIFN-α + SOF + RBV was higher than willingness-to-pay threshold (WPT), whereas in the group of patients with cirrhosis ICERDasabuvir + Ombitasvir/paritaprevir/ritonavir + RBV vs PegIFN-α + SOF + RBV was lower than WPT. Using “budget impact” analysis it was shown that switching to PegIFN-α + SOF + RBV from PegIFN-α + RBV regimen will involve extra direct costs for antiviral treatment (AVT), but will lead to a reduction in medical aid costs to the patients not reaching SVR, patients with CHC complications and, as a consequence, will lead to a reduction in cumulative medical costs. Moreover, transition from PegIFN-α + SMV + RBV, Dasabuvir + Ombitasvir/paritaprevir/ ritonavir and Dasabuvir + Ombitasvir/paritaprevir/ritonavir + RBV to PegIFN-α + SOF + RBV will lead to a reduction in both AVT costs and cumulative medical costs.

Glushchenko A.A., Kulikov A.Y., Yagudina R.I. 1526

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.

Kulikov A.Y., Protsenko M.V. 1093

First Moscow State Medical University I.M. Sechenov (Sechenov University), Moscow, Russia

Kulikov A.Y., Protsenko M.V., Serpik V.G. 882

The article presents updated and advanced results of a pharmacoeconomic study conducted in 2016 on the treatment of patients with pulmonary arterial hypertension II and III functional classes with ambrisentan and bosentan preparations in Russia. The evaluation was provided through cost analysis, “cost minimization” analysis, “cost-utility” analysis, “budget impact” analysis. Еhe cost of pharmacotherapy with Volibrys (ambrisentan) of arterial pulmonary hypertension, regardless of the functional class, was 1 200 000 rubles. and 1 300 000 rubles. respectively, with the need for 12 and 13 packs of the drug per year. The average annual cost of treatment with bosentan ranges from 1 368 900 rubles. up to 1 471 644 rubles. respectively, with the need for 13 and 14 packs of the drug. The results of the “cost minimization” analysis, carried out on the assumption of equal effectiveness of ambrisentan and bosentan, showed that per one patient for one year, the preparation of Volibris (ambrisentan) in comparison with the preparations of bosentan (Traklir and Bozeneks) 175 760 to 178 504 rubles. The values of the “cost-utility” coefficient for ambrisentan in the treatment of pulmonary arterial hypertension II and III of the functional class varied depending on the dosage (5 or 10 mg) from 1,831,563 rubles. up to 2 012 040 rubles for QALY and 2 667 711 rubles up to 2 787 728 rubles. for QALY. At the same time, similar averaged values for bosentan amounted to 2 480 073 rubles and 3 271 174 rubles for QALY for II and III functional class pulmonary arterial hypertension, respectively. The “budget impact” analysis based on the estimated number of patients with pulmonary arterial hypertension in the Russian Federation, which is 2936 people, showed that the transfer of this number of patients treated with the bosentan in the form of original (Tracler) and reproduced (Bozeneks) 1: 1, for treatment with the drug ambrisentan (Volibris), will allow for 2 years to save 853.2 million rubles, which is 9.7% of the budget required for the treatment of bosentan.

Kulikov A.Y., Makarova E.I. 821

High lability of the clinical aspect of asthma, poor observation of medical recommendations and low treatment adherence, make it necessary to search ways to optimize approaches to regimens of asthma therapy. According to GINA, not only correctly selected therapy but also the correct use of an inhalation device, increases control of the disease. Incorrect inhalation techniques affect the effectiveness of treatment and can lead to increased health system costs and a decrease in the patients’ quality of life. Objective. In this regard, the objective of this study was to conduct a comparative pharmacoeconomic evaluation of the use of vilanterol + fluticasone furoate (Relvar Ellipta) and budesonide + formoterol (Symbicort® Turbuhaler®) delivered with various inhalation devices. Materials and methods. Based on the clinical trials data on the effectiveness of the comparative treatment regimens, data on the cost of medical products, medical services, and the frequency of their provision, the effectiveness criteria were selected, their final values were modeled, cost analysis, cost-effectiveness and budget impact analysis were conduct- ed. Results. The cost analysis educed that the amounts of direct costs of asthma therapy with vilanterol + fluticasone furoate 22 μg + 184 μg / dose is 49% lower than the costs of treatment with high doses of budesonide + formoterol, the use of vilanterol + fluticasone furoate 22 mcg + 92 mcg / dose is 36% lower than the costs of asthma with medium doses of budesonide + formoterol, and is equal to the sum of direct costs of treating asthma with low-dose budesonide + formoterol. The «cost-effectiveness» analysis demonstrated that the therapy of vilanterol + fluticasone furoate in both dosages is dominant compared to therapy with equiv- alent medium and high doses of budesonide + formoterol. The budget impact analysis showed that the switching of 186,394 patients suffering from asthma from budesonide + formoterol to vilanterol + fluticasone furoate would result in savings of total direct costs of up to 6.2 billion rubles per year. Conclusion. Based on the results of the study, the pharmacoeconomic reasonability of use of vilanterol + fluticasone furoate, delivered by the Ellipta inhalation device, was established in the treatment of patients suffering from asthma.

Goloenko N.G., Evstigneeva L.., Zhilyaev E.., Korotaeva T.., Kulikov A.Y., Logvinuk P.A., Lytkina K.., Protsenko M.V., Serpik V.G., Yagudina R.I. 569

Possessing a high prevalence and disability, psoriatic arthritis (PsA) is a serious socio-economic burden for the patient and for society. Therefore, the choice of the PsA treatment strategy requires focusing on not only the prevention and control of the disease but also the effective allocation of the available resources of the healthcare system. Objective. In this regard, the purpose of this study was to conduct a comparative pharmacoeconomic evaluation of biologics: secukinumab (Cosentyx), golimumab (Simponi®), certolizumab pegol (Cimzia®), Ustekinumab (Stelara®), adalimumab (Humira®), etanercept (Enbrel®) and infliximab (Remicade®, Flammegis®, Infliximab produced by local BIOCAD company). Materials and methods. Based on data on the effectiveness of compared treatment regimens, data on the cost of drugs and medical services, as well as the frequency of their provision, an analysis of direct costs, cost-effectiveness analysis, as well as budget impact analysis were carried out. Results. The cost analysis educed that the amount of direct costs for treatment with secukinumab 150 mg for ‘biologic-naive’ patients with active PsA is on average 28% and 40% lower than the cost of treatment with certolizumab pegol, golimumab, ustekinumab, adalimumab, etanercept and infliximab in the first and subsequent years of therapy, in accordance. Estimation of costs and efficacy showed that treatment of PsA with secukinumab 150 mg is characterized by lower costs per unit of effectiveness (ACR 20/50/70 response), relative to the indicators of the compared drugs in the first and subsequent years of therapy. The assumed prescription of secukinumab instead of certolizumab pegol, golimumab, ustekinumab, adalimumab, etanercept, and infliximab (including biosimilar) 19% of patients with active PsA leads to budget savings of 468 million rubles and 1.5 billion rubles for the first and three years of treatment, in accordance, on the calculated patient population. Conclusion. According to the results of the study, the pharmacoeconomic feasibility of using secukinumab 150 mg as a first-line line biologic for the treatment of active PsA has been established.

Kostina E.O., Kulikov A.Y., Serpik V.G., Yagudina R.I. 578

The fifth year in the system of state drug provision at the federal level, the Decree of the Government of the Russian Federation N871 of 08.28.2014 introduced the requirement of pharmacoeconomic evaluation of drugs when they are included in the lists of drugs. At the end of 2018, the second edition of this document was adopted and brought dramatic changes to the rules of pharmacoeconomic evaluation. This fact prompted us to conduct a comparative analysis of the old and new versions of the document from the point of view of pharmacoeconomics in order to retrospectively identify and systematize the shortcomings and advantages of the rules of pharmacoeconomic evaluation given by the original version of the document and prospectively determine to what extent the new version of the Russian Federation Resolution N871 of 28.08. 2014 (ed. From 10.29.2018) managed to overcome the identified problems and whether it contains any new contradictions. The adoption of the first edition of the Decree of the Government of the Russian Federation N871 of 08.28.2014 approved the mandatory status of pharmacoeconomic evaluation when including drugs in the lists. At the same time, practical experience in applying the developed rules for pharmacoeconomic evaluation revealed their imbalance: due to the minimum number of scores received by a drug according to the cost-effectiveness analysis, the probability of including innovative or even modern effective drugs in the lists was very small. The lack of clear requirements for the interpretation of the results of the cost-effectiveness analysis (and the incremental cost- effectiveness analysis), the conduct of the budget impact analysis and the selection of comparative drugs with an unbalanced integral scale led to pharmacoeconomic studies aimed at achieving positive pharmacoeconomic evaluation (preparation of the minimum required number of points on an integrated scale). The new version of the document largely corrected the lack of the first version of the rules, increasing the number of scores awarded by the cost-effectiveness analysis and introducing various scenarios of this analysis method, which undoubtedly should make the new rules more focused on the evaluation of innovative and effective drugs. At the same time, the “country-specific” methodology for assessing the results of the incremental cost-effectiveness analysis was included in the updated rules. It can be predicted with high probability that an insufficiently complete and accurate description of it in Government Decree N871 of August 28, 2014 (as amended on 10.29.2018) will cause discrepancies in the integral scoring of this type of analysis, creating difficulties for all participants in the listing process: for customers of pharmacoeconomic evaluations, researchers, as well as expert organizations. Attention is drawn to the contradictions that arise when evaluating drugs according to the “cost minimization” analysis scenario, in which the required minimum passing score does not provide for the very fact of cost savings on the considered drug, but only the condition that the savings will exceed 20%. Unfortunately, the new version of the document did not solve the problem of the validity of the used gradation of the integral score scale, and moreover, this problem was increased, violating the logic of interpretation of the results of the cost-effectiveness analysis and the cost-effectiveness incremental analysis.

Krylov V.A., Kulikov A.Y., Yagudina R.I. 529

Infertility is successfully treated by IVF and ICSI methods. One of the most important stages in IVF protocol is control ovarian stimulation (COS). There are recombinant and menopausal drugs to develop and mature oocyte. In this article was compared the economic efficiency of follitropin-alpha+lutropin-alpha vs follitropin-alpa+menotropin vs menotropin based on cost-effectiveness, budget impact analysis. Folliropin-alpha+lutropin-alpha cost of treating per one patient estimate 51 520 rubles, menotropin – 49 104 rubles, follitropin- alpa+menotropin - 61 298 rubles. Cost-effectiveness analysis, provided on the number of retrieved oocytes, rate of implantation and rate of clinical pregnancy, shown that follitropin-alpha+lutropin-alpha is dominant therapy. According to the results of the budget impact analysis, the increasing use of follitropin- alpha+lutropin-alpha on the market to 51.5% will save 29.2 million rubles.

Kulikov A.Y., Kulikov V.., Serpik V.G. 512

Currently, there are more and more cases of switching between drugs belonging to the same pharmacological group in favor of a drug with a lower cost. However, it is important to note that from the point of view of the overall economic effect of the use of a medicinal product, its market value may not be the main cost driver. Against this background, for rational prescribing of drugs and efficient use of resources of the health care system, first of all, attention should be paid to other factors characterizing medicines. In order to examine the actualized problem on a practical example, we carried out pharmacoeconomic research of two drugs for the treatment of type 2 diabetes from the group of selective inhibitors of dipeptypeptidase (DPP-4) - alogliptin and vildagliptin. The aim of the study was to establish whether the transition to an alternative, characterized by a lower cost, will be accompanied by savings in the health care system. The results of the pharmacoeconomic analysis obtained by the authors showed that “switching” patients from the drug vildagliptin to the medicinal drug alogliptin in order to save the health budget is an erroneous strategy, since according to the meta-analysis based on the Juan Ling et all, 2018. As result are total costs higher, increased complications and worse control of diabetes.

Kulikov A.Y., Novikov I.V. 378

Purpose of the study: Determine whether linagliptin is a pharmacoeconomically sound choice when it is included in therapy in patients with insufficient glycemic control, receiving the maximum tolerated dose of metformin in monotherapy, or in combination with sulfonylurea derivatives or thiazolidinediones, as well as in comparison with the IPDP-4 preparations present on the market St. Petersburg.

Kulikov A.Y., Serpik V.G., Yagudina R.I. 393

The article presents the concept of the development of the methodology of cost-effectiveness analysis. The classic cost-effectiveness analysis allows us to determine the cost per unit of efficiency of the technologies under consideration. If one of the technologies, which is characterized by the greatest efficiency, also has a minimum value of CER, then it is considered strictly preferable. The CER in this case reflects the cost of achieving the unit of efficiency on this technology. If the more expensive technology, which is more efficient, is also characterized by a large value of the cost-effectiveness ratio, then there is a need for an incremental cost-effectiveness analysis. Its result is a calculated incremental cost-effectiveness ratio (ICER), which reflects the additional cost of additional efficiency on a more efficient technology. Thus, the result of the incremental cost-effectiveness analysis directly depends on the choice of comparison technology, as well as the presence (or absence) of these alternatives on the market, and even the order of their registration in the country. The degree of acceptance by the health authorities of the notion of a “willingness to pay” threshold directly affects decisions made. In this regard, against the background of the registration of new innovative technologies, innovative approaches to their assessment are also required, which will adequately reflect in the assessment the factors of innovation and the increase in technology efficiency. This article presents the concept of the development of the cost- effectiveness analysis methodology with the transition to a new method of pharmacoeconomic evaluation - an analysis of the «relative value», which allows solving a number of methodological problems and making decisions under conditions of greater certainty.

Kulikov A.Y., Litvinenko M.M., Yagudina R.I. 373

In the first part of this publication, the methodology of analyzing the “cost of the disease”, the specifics of its calculation in the conditions of public health of the Russian Federation, various levels of research are considered in detail. The second part of the article is devoted to the presentation of the results of the first domestic study of the economic burden of multiple sclerosis, based on Russian data. The direct and indirect costs associated with multiple sclerosis were calculated. The results of the pharmacoeconomic analysis showed that the economic burden per patient per year depends on the form of the type of the underlying disease and amounts to 418,954 rubles for patients with a remitting type of flow, 556,150 rubles for patients with a returnable progressive type of flow with primary progressive course of multiple sclerosis. For the first time it has been shown that the ratio of direct and indirect costs for multiple sclerosis depends on the type of flow: with a remitting type of flow, direct costs prevail and they account for 65.7%, while for a backward-progressive and primary-progressive, a larger volume is occupied indirect costs, and they are 63.9% and 68.2%, respectively.

Kulikov A.Y., Pochuprina A.A., Serpik V.G. 371

Basal cell carcinoma (BCC) is the most common non-melanocytic skin cancer and is a tumor of the basal layer of the epidermis and hair follicles. Patients with a history of locally advanced or metastatic forms of BPC, undergo surgical treatment or radiation therapy. Until now, in the absence of the effectiveness of these methods, palliative medical care was provided to the patient with CCB. The emergence of a molecular-directed drug, vismodegib (Erivedge ™), opens up new prospects for the treatment of these forms of BPC and requires justification of its use in BPC patients with the help of health technology assessment (HTA). In the decision-making process regarding the implementation of this treatment method for patients with locally advanced and metastatic BPC, it is necessary to take into account both economic, clinical components and social significance, since the use of vismodehyb represents the only possibility of treating patients with these forms of BPC, surgical method and radiation therapy is not applicable.

Kostina E.O., Kulikov A.Y. 279

As part of this work, a pharmacoeconomic study of drugs used in enzyme replacement therapy (ERT) of patients with mucopolysaccharidosis (MPS) type II: idursulfase and idursulfase beta was carried out. As a result, it was found that the use of the drug idursulfase beta, is a more pharmacoeconomically beneficial treatment regimen for patients with MPS type II. Saving money when switching one patient from idursulfase to idursulfase beta makes up for one year - 7 377 746 rubles, for 5 years - 36 888 728 rubles. During the budget impact analysis, it was determined that an increase in the proportion of patients up to 50% in the idursulfase beta will make it possible to achieve an overall savings of 796 845 270 rubles. for 5 years. The missed opportunities analysis showed that an additional 28 patients could be treated with money saved as a result of a change in treatment strategy.

Arinina E.E., Kostina E.O., Kulikov A.Y., .., Serpik V.G., Yagudina R.I. 76

The aim of the research was a comparative analysis of the economic consequences of smoking in the Russian Federation (from 2009 to 2018). The analysis included calculations direct (costs the cost of economicburden of tobacco-related diseases) and indirect costs (losses gross domestic product (GDP) due to premature disability, premature death, reduced productivity, damage from fires due to smoking). As a result of the study, it was determined that the total economic damage from smoking in 2018 amounted to 5 604 billion rubles, which amounted to about 5.4% of GDP for the year. Compared to 2016, the economic burden of smoking increased by 46% (including inflation).

Kulikov A.Y., Protsenko M.V., Serpik V.G., Sobolev N.P. 85

Wide range of available platforms for phacoemulsification of cataracts and limited financing of the health care system make crucial of optimal decisions in choosing specific models of platforms. In this regard, for the first time in Russia and in the world, an assessment of healthcare technology (HTA) of 6 platforms for cataract phacoemulsification was carried out - Centurion, Infiniti, Stellaris, Stellaris PC, Whitestar Signature, Visalis 500. Our study revealed the limitations of the existing evidence base for comparative purposes evaluations of various phacoemulsification platforms from a health system perspective. Due to this we made an assumption of the use expert assessment of the analized platforms in terms of ultrasound time and the volume of aspirated liquid allowed us to provide HTA, the results of which on the one hand confirm the applicability of the HTA methodology itself for the analysis of the type of medical device under consideration, and with available cost data demonstrated «cost-effectiveness ”of the Centurion platform and its advantage in terms of budget impact analysis among other platforms of the latest generation. The full use of HTA for cataract phacoemulsification platforms requires the creation of an evidence base, taking into account perspective of organizational decision-making process.

1 | 2 | 3 | 4
Babiy V.V., Kulikov A.Y. 1576

The objectives of this study were to determine the most advantageous antiviral therapy option for chronic hepatitis C (CHC) (peginterferon alfa + ribavirin (PegIFN + RBV) 48 weeks (F0–F4), peginterferon alfa + simeprevir + ribavirin (PegIFN + SMV + RBV) 24 weeks (F0–F4), peginterferon alfa + sofosbuvir + ribavirin (PegIFN + SOF + RBV) 12 weeks (F0–F4), dasabuvir + ombitasvir/paritaprevir/ritonavir (Dasabuvir + Ombitasvir/ paritaprevir/ritonavir) 12 weeks (F0–F3) and dasabuvir + ombitasvir/ paritaprevir/ritonavir + ribavirin (Dasabuvir + Ombitasvir/paritaprevir/ritonavir + RBV) 12 weeks (F4)) among treatment-naive and treatment-experienced patients (HCV genotype 1) based on the comparison of cost-effectiveness ratios and economic outcomes (“budget impact” analysis) from implementing the treatment strategy PegIFN-α + SOF + RBV instead of PegIFN-α + RBV, PegIFN-α + SIM + RBV and Dasabuvir + Ombitasvir/paritaprevir/ritonavir. Model-based pharmacoeconomic analysis has been conducted. The costeffectiveness analysis showed that independently of the former treatment experience of CHC (genotype 1) patients the combination PegIFN-α + SOF + RBV was a predominant regimen as compared to PegIFN-α + RBV and PegIFN-α + SMV + RBV. In the groups of patients without cirrhosis and with cirrhosis the highest QALY value was noted for Dasabuvir + Ombitasvir/ paritaprevir/ritonavir and Dasabuvir + Ombitasvir/paritaprevir/ritonavir + RBV combinations, respectively. Also a smaller cost-effectiveness ratio (CER) relative to the two above regimens was noted for PegIFN-α + SOF + RBV. In the group of treatment-naive patients without cirrhosis incremental costeffectiveness ratio (ICER) of Dasabuvir + Ombitasvir/paritaprevir/ritonavir vs PegIFN-α + SOF + RBV was higher than willingness-to-pay threshold (WPT), whereas in the group of patients with cirrhosis ICERDasabuvir + Ombitasvir/paritaprevir/ritonavir + RBV vs PegIFN-α + SOF + RBV was lower than WPT. Using “budget impact” analysis it was shown that switching to PegIFN-α + SOF + RBV from PegIFN-α + RBV regimen will involve extra direct costs for antiviral treatment (AVT), but will lead to a reduction in medical aid costs to the patients not reaching SVR, patients with CHC complications and, as a consequence, will lead to a reduction in cumulative medical costs. Moreover, transition from PegIFN-α + SMV + RBV, Dasabuvir + Ombitasvir/paritaprevir/ ritonavir and Dasabuvir + Ombitasvir/paritaprevir/ritonavir + RBV to PegIFN-α + SOF + RBV will lead to a reduction in both AVT costs and cumulative medical costs.

Glushchenko A.A., Kulikov A.Y., Yagudina R.I. 1526

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.

Kulikov A.Y., Protsenko M.V. 1093

First Moscow State Medical University I.M. Sechenov (Sechenov University), Moscow, Russia

Kulikov A.Y., Protsenko M.V., Serpik V.G. 882

The article presents updated and advanced results of a pharmacoeconomic study conducted in 2016 on the treatment of patients with pulmonary arterial hypertension II and III functional classes with ambrisentan and bosentan preparations in Russia. The evaluation was provided through cost analysis, “cost minimization” analysis, “cost-utility” analysis, “budget impact” analysis. Еhe cost of pharmacotherapy with Volibrys (ambrisentan) of arterial pulmonary hypertension, regardless of the functional class, was 1 200 000 rubles. and 1 300 000 rubles. respectively, with the need for 12 and 13 packs of the drug per year. The average annual cost of treatment with bosentan ranges from 1 368 900 rubles. up to 1 471 644 rubles. respectively, with the need for 13 and 14 packs of the drug. The results of the “cost minimization” analysis, carried out on the assumption of equal effectiveness of ambrisentan and bosentan, showed that per one patient for one year, the preparation of Volibris (ambrisentan) in comparison with the preparations of bosentan (Traklir and Bozeneks) 175 760 to 178 504 rubles. The values of the “cost-utility” coefficient for ambrisentan in the treatment of pulmonary arterial hypertension II and III of the functional class varied depending on the dosage (5 or 10 mg) from 1,831,563 rubles. up to 2 012 040 rubles for QALY and 2 667 711 rubles up to 2 787 728 rubles. for QALY. At the same time, similar averaged values for bosentan amounted to 2 480 073 rubles and 3 271 174 rubles for QALY for II and III functional class pulmonary arterial hypertension, respectively. The “budget impact” analysis based on the estimated number of patients with pulmonary arterial hypertension in the Russian Federation, which is 2936 people, showed that the transfer of this number of patients treated with the bosentan in the form of original (Tracler) and reproduced (Bozeneks) 1: 1, for treatment with the drug ambrisentan (Volibris), will allow for 2 years to save 853.2 million rubles, which is 9.7% of the budget required for the treatment of bosentan.

Kulikov A.Y., Makarova E.I. 821

High lability of the clinical aspect of asthma, poor observation of medical recommendations and low treatment adherence, make it necessary to search ways to optimize approaches to regimens of asthma therapy. According to GINA, not only correctly selected therapy but also the correct use of an inhalation device, increases control of the disease. Incorrect inhalation techniques affect the effectiveness of treatment and can lead to increased health system costs and a decrease in the patients’ quality of life. Objective. In this regard, the objective of this study was to conduct a comparative pharmacoeconomic evaluation of the use of vilanterol + fluticasone furoate (Relvar Ellipta) and budesonide + formoterol (Symbicort® Turbuhaler®) delivered with various inhalation devices. Materials and methods. Based on the clinical trials data on the effectiveness of the comparative treatment regimens, data on the cost of medical products, medical services, and the frequency of their provision, the effectiveness criteria were selected, their final values were modeled, cost analysis, cost-effectiveness and budget impact analysis were conduct- ed. Results. The cost analysis educed that the amounts of direct costs of asthma therapy with vilanterol + fluticasone furoate 22 μg + 184 μg / dose is 49% lower than the costs of treatment with high doses of budesonide + formoterol, the use of vilanterol + fluticasone furoate 22 mcg + 92 mcg / dose is 36% lower than the costs of asthma with medium doses of budesonide + formoterol, and is equal to the sum of direct costs of treating asthma with low-dose budesonide + formoterol. The «cost-effectiveness» analysis demonstrated that the therapy of vilanterol + fluticasone furoate in both dosages is dominant compared to therapy with equiv- alent medium and high doses of budesonide + formoterol. The budget impact analysis showed that the switching of 186,394 patients suffering from asthma from budesonide + formoterol to vilanterol + fluticasone furoate would result in savings of total direct costs of up to 6.2 billion rubles per year. Conclusion. Based on the results of the study, the pharmacoeconomic reasonability of use of vilanterol + fluticasone furoate, delivered by the Ellipta inhalation device, was established in the treatment of patients suffering from asthma.

Krylov V.A., Kulikov A.Y., Yagudina R.I. 529

Infertility is successfully treated by IVF and ICSI methods. One of the most important stages in IVF protocol is control ovarian stimulation (COS). There are recombinant and menopausal drugs to develop and mature oocyte. In this article was compared the economic efficiency of follitropin-alpha+lutropin-alpha vs follitropin-alpa+menotropin vs menotropin based on cost-effectiveness, budget impact analysis. Folliropin-alpha+lutropin-alpha cost of treating per one patient estimate 51 520 rubles, menotropin – 49 104 rubles, follitropin- alpa+menotropin - 61 298 rubles. Cost-effectiveness analysis, provided on the number of retrieved oocytes, rate of implantation and rate of clinical pregnancy, shown that follitropin-alpha+lutropin-alpha is dominant therapy. According to the results of the budget impact analysis, the increasing use of follitropin- alpha+lutropin-alpha on the market to 51.5% will save 29.2 million rubles.

Kulikov A.Y., Kulikov V.., Serpik V.G. 512

Currently, there are more and more cases of switching between drugs belonging to the same pharmacological group in favor of a drug with a lower cost. However, it is important to note that from the point of view of the overall economic effect of the use of a medicinal product, its market value may not be the main cost driver. Against this background, for rational prescribing of drugs and efficient use of resources of the health care system, first of all, attention should be paid to other factors characterizing medicines. In order to examine the actualized problem on a practical example, we carried out pharmacoeconomic research of two drugs for the treatment of type 2 diabetes from the group of selective inhibitors of dipeptypeptidase (DPP-4) - alogliptin and vildagliptin. The aim of the study was to establish whether the transition to an alternative, characterized by a lower cost, will be accompanied by savings in the health care system. The results of the pharmacoeconomic analysis obtained by the authors showed that “switching” patients from the drug vildagliptin to the medicinal drug alogliptin in order to save the health budget is an erroneous strategy, since according to the meta-analysis based on the Juan Ling et all, 2018. As result are total costs higher, increased complications and worse control of diabetes.

Goloenko N.G., Evstigneeva L.., Zhilyaev E.., Korotaeva T.., Kulikov A.Y., Logvinuk P.A., Lytkina K.., Protsenko M.V., Serpik V.G., Yagudina R.I. 569

Possessing a high prevalence and disability, psoriatic arthritis (PsA) is a serious socio-economic burden for the patient and for society. Therefore, the choice of the PsA treatment strategy requires focusing on not only the prevention and control of the disease but also the effective allocation of the available resources of the healthcare system. Objective. In this regard, the purpose of this study was to conduct a comparative pharmacoeconomic evaluation of biologics: secukinumab (Cosentyx), golimumab (Simponi®), certolizumab pegol (Cimzia®), Ustekinumab (Stelara®), adalimumab (Humira®), etanercept (Enbrel®) and infliximab (Remicade®, Flammegis®, Infliximab produced by local BIOCAD company). Materials and methods. Based on data on the effectiveness of compared treatment regimens, data on the cost of drugs and medical services, as well as the frequency of their provision, an analysis of direct costs, cost-effectiveness analysis, as well as budget impact analysis were carried out. Results. The cost analysis educed that the amount of direct costs for treatment with secukinumab 150 mg for ‘biologic-naive’ patients with active PsA is on average 28% and 40% lower than the cost of treatment with certolizumab pegol, golimumab, ustekinumab, adalimumab, etanercept and infliximab in the first and subsequent years of therapy, in accordance. Estimation of costs and efficacy showed that treatment of PsA with secukinumab 150 mg is characterized by lower costs per unit of effectiveness (ACR 20/50/70 response), relative to the indicators of the compared drugs in the first and subsequent years of therapy. The assumed prescription of secukinumab instead of certolizumab pegol, golimumab, ustekinumab, adalimumab, etanercept, and infliximab (including biosimilar) 19% of patients with active PsA leads to budget savings of 468 million rubles and 1.5 billion rubles for the first and three years of treatment, in accordance, on the calculated patient population. Conclusion. According to the results of the study, the pharmacoeconomic feasibility of using secukinumab 150 mg as a first-line line biologic for the treatment of active PsA has been established.

Kostina E.O., Kulikov A.Y., Serpik V.G., Yagudina R.I. 578

The fifth year in the system of state drug provision at the federal level, the Decree of the Government of the Russian Federation N871 of 08.28.2014 introduced the requirement of pharmacoeconomic evaluation of drugs when they are included in the lists of drugs. At the end of 2018, the second edition of this document was adopted and brought dramatic changes to the rules of pharmacoeconomic evaluation. This fact prompted us to conduct a comparative analysis of the old and new versions of the document from the point of view of pharmacoeconomics in order to retrospectively identify and systematize the shortcomings and advantages of the rules of pharmacoeconomic evaluation given by the original version of the document and prospectively determine to what extent the new version of the Russian Federation Resolution N871 of 28.08. 2014 (ed. From 10.29.2018) managed to overcome the identified problems and whether it contains any new contradictions. The adoption of the first edition of the Decree of the Government of the Russian Federation N871 of 08.28.2014 approved the mandatory status of pharmacoeconomic evaluation when including drugs in the lists. At the same time, practical experience in applying the developed rules for pharmacoeconomic evaluation revealed their imbalance: due to the minimum number of scores received by a drug according to the cost-effectiveness analysis, the probability of including innovative or even modern effective drugs in the lists was very small. The lack of clear requirements for the interpretation of the results of the cost-effectiveness analysis (and the incremental cost- effectiveness analysis), the conduct of the budget impact analysis and the selection of comparative drugs with an unbalanced integral scale led to pharmacoeconomic studies aimed at achieving positive pharmacoeconomic evaluation (preparation of the minimum required number of points on an integrated scale). The new version of the document largely corrected the lack of the first version of the rules, increasing the number of scores awarded by the cost-effectiveness analysis and introducing various scenarios of this analysis method, which undoubtedly should make the new rules more focused on the evaluation of innovative and effective drugs. At the same time, the “country-specific” methodology for assessing the results of the incremental cost-effectiveness analysis was included in the updated rules. It can be predicted with high probability that an insufficiently complete and accurate description of it in Government Decree N871 of August 28, 2014 (as amended on 10.29.2018) will cause discrepancies in the integral scoring of this type of analysis, creating difficulties for all participants in the listing process: for customers of pharmacoeconomic evaluations, researchers, as well as expert organizations. Attention is drawn to the contradictions that arise when evaluating drugs according to the “cost minimization” analysis scenario, in which the required minimum passing score does not provide for the very fact of cost savings on the considered drug, but only the condition that the savings will exceed 20%. Unfortunately, the new version of the document did not solve the problem of the validity of the used gradation of the integral score scale, and moreover, this problem was increased, violating the logic of interpretation of the results of the cost-effectiveness analysis and the cost-effectiveness incremental analysis.

Kulikov A.Y., Litvinenko M.M., Yagudina R.I. 373

In the first part of this publication, the methodology of analyzing the “cost of the disease”, the specifics of its calculation in the conditions of public health of the Russian Federation, various levels of research are considered in detail. The second part of the article is devoted to the presentation of the results of the first domestic study of the economic burden of multiple sclerosis, based on Russian data. The direct and indirect costs associated with multiple sclerosis were calculated. The results of the pharmacoeconomic analysis showed that the economic burden per patient per year depends on the form of the type of the underlying disease and amounts to 418,954 rubles for patients with a remitting type of flow, 556,150 rubles for patients with a returnable progressive type of flow with primary progressive course of multiple sclerosis. For the first time it has been shown that the ratio of direct and indirect costs for multiple sclerosis depends on the type of flow: with a remitting type of flow, direct costs prevail and they account for 65.7%, while for a backward-progressive and primary-progressive, a larger volume is occupied indirect costs, and they are 63.9% and 68.2%, respectively.

Kulikov A.Y., Novikov I.V. 378

Purpose of the study: Determine whether linagliptin is a pharmacoeconomically sound choice when it is included in therapy in patients with insufficient glycemic control, receiving the maximum tolerated dose of metformin in monotherapy, or in combination with sulfonylurea derivatives or thiazolidinediones, as well as in comparison with the IPDP-4 preparations present on the market St. Petersburg.

Kulikov A.Y., Pochuprina A.A., Serpik V.G. 371

Basal cell carcinoma (BCC) is the most common non-melanocytic skin cancer and is a tumor of the basal layer of the epidermis and hair follicles. Patients with a history of locally advanced or metastatic forms of BPC, undergo surgical treatment or radiation therapy. Until now, in the absence of the effectiveness of these methods, palliative medical care was provided to the patient with CCB. The emergence of a molecular-directed drug, vismodegib (Erivedge ™), opens up new prospects for the treatment of these forms of BPC and requires justification of its use in BPC patients with the help of health technology assessment (HTA). In the decision-making process regarding the implementation of this treatment method for patients with locally advanced and metastatic BPC, it is necessary to take into account both economic, clinical components and social significance, since the use of vismodehyb represents the only possibility of treating patients with these forms of BPC, surgical method and radiation therapy is not applicable.

Kulikov A.Y., Serpik V.G., Yagudina R.I. 393

The article presents the concept of the development of the methodology of cost-effectiveness analysis. The classic cost-effectiveness analysis allows us to determine the cost per unit of efficiency of the technologies under consideration. If one of the technologies, which is characterized by the greatest efficiency, also has a minimum value of CER, then it is considered strictly preferable. The CER in this case reflects the cost of achieving the unit of efficiency on this technology. If the more expensive technology, which is more efficient, is also characterized by a large value of the cost-effectiveness ratio, then there is a need for an incremental cost-effectiveness analysis. Its result is a calculated incremental cost-effectiveness ratio (ICER), which reflects the additional cost of additional efficiency on a more efficient technology. Thus, the result of the incremental cost-effectiveness analysis directly depends on the choice of comparison technology, as well as the presence (or absence) of these alternatives on the market, and even the order of their registration in the country. The degree of acceptance by the health authorities of the notion of a “willingness to pay” threshold directly affects decisions made. In this regard, against the background of the registration of new innovative technologies, innovative approaches to their assessment are also required, which will adequately reflect in the assessment the factors of innovation and the increase in technology efficiency. This article presents the concept of the development of the cost- effectiveness analysis methodology with the transition to a new method of pharmacoeconomic evaluation - an analysis of the «relative value», which allows solving a number of methodological problems and making decisions under conditions of greater certainty.

Kostina E.O., Kulikov A.Y. 279

As part of this work, a pharmacoeconomic study of drugs used in enzyme replacement therapy (ERT) of patients with mucopolysaccharidosis (MPS) type II: idursulfase and idursulfase beta was carried out. As a result, it was found that the use of the drug idursulfase beta, is a more pharmacoeconomically beneficial treatment regimen for patients with MPS type II. Saving money when switching one patient from idursulfase to idursulfase beta makes up for one year - 7 377 746 rubles, for 5 years - 36 888 728 rubles. During the budget impact analysis, it was determined that an increase in the proportion of patients up to 50% in the idursulfase beta will make it possible to achieve an overall savings of 796 845 270 rubles. for 5 years. The missed opportunities analysis showed that an additional 28 patients could be treated with money saved as a result of a change in treatment strategy.

Arinina E.E., Kostina E.O., Kulikov A.Y., .., Serpik V.G., Yagudina R.I. 76

The aim of the research was a comparative analysis of the economic consequences of smoking in the Russian Federation (from 2009 to 2018). The analysis included calculations direct (costs the cost of economicburden of tobacco-related diseases) and indirect costs (losses gross domestic product (GDP) due to premature disability, premature death, reduced productivity, damage from fires due to smoking). As a result of the study, it was determined that the total economic damage from smoking in 2018 amounted to 5 604 billion rubles, which amounted to about 5.4% of GDP for the year. Compared to 2016, the economic burden of smoking increased by 46% (including inflation).

Kulikov A.Y., Protsenko M.V., Serpik V.G., Sobolev N.P. 85

Wide range of available platforms for phacoemulsification of cataracts and limited financing of the health care system make crucial of optimal decisions in choosing specific models of platforms. In this regard, for the first time in Russia and in the world, an assessment of healthcare technology (HTA) of 6 platforms for cataract phacoemulsification was carried out - Centurion, Infiniti, Stellaris, Stellaris PC, Whitestar Signature, Visalis 500. Our study revealed the limitations of the existing evidence base for comparative purposes evaluations of various phacoemulsification platforms from a health system perspective. Due to this we made an assumption of the use expert assessment of the analized platforms in terms of ultrasound time and the volume of aspirated liquid allowed us to provide HTA, the results of which on the one hand confirm the applicability of the HTA methodology itself for the analysis of the type of medical device under consideration, and with available cost data demonstrated «cost-effectiveness ”of the Centurion platform and its advantage in terms of budget impact analysis among other platforms of the latest generation. The full use of HTA for cataract phacoemulsification platforms requires the creation of an evidence base, taking into account perspective of organizational decision-making process.

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Professor of the Department of organization of drug supply and pharmacoeconomics, leading researcher pharmacoeconomic studies of the Laboratory Research Institute of Pharmacy, First MGMU them. IM Sechenov. Moscow, Russia