# Serpik Vjacheslav Gennadievich

Abstract: We provided a pharmacoeconomic evaluation of the treatment of gastric cancer in the second line of therapy with ramucirumab, using the relative value analysis method. Ramucirumab is the only anti-angiogenic drug registered for the treatment of advanced gastric cancer. In comparison with the standard regimens of the second line of chemotherapy for gastric cancer, the use of the ramucirumab has a statistically significant advantage, increasing the median overall survival by 30%. Ramucirumab (Cyramza) cost of treating per one patient is 1 761 564 RUB. From the perspective of relative value analysis the cost of an additional unit of effectiveness of ramucirumab is comparable or even lower than the same criteria of other antitumor drugs of monoclonal antibodies already included in the national EDL. Consequently, ramucirumab can be characterized as an acceptable technology. The budget impact analysis showed that providing patients with advanced gastric cancer with the ramucirumab is characterized by a lower burden on the drug support budget for oncological patients than bevacizumab, trastuzumab and cetuximab in the therapy of the oncology nosologies, at the their approval date. According to the results of the budget impact analysis on the drug supply of ramucirumab, 200 patients will additionally require 329.19 million rubles, which is only 0.64% of the budget for the treatment of cancer in 2016. Key words: gastric cancer, pharmacoeconomics, cost-effectiveness analysis, budget impact analysis, relative value analysis, bevacizumab, cetuximab, ramucirumab, trastuzumab.

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.

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.

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.

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.

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Abstract: We provided a pharmacoeconomic evaluation of the treatment of gastric cancer in the second line of therapy with ramucirumab, using the relative value analysis method. Ramucirumab is the only anti-angiogenic drug registered for the treatment of advanced gastric cancer. In comparison with the standard regimens of the second line of chemotherapy for gastric cancer, the use of the ramucirumab has a statistically significant advantage, increasing the median overall survival by 30%. Ramucirumab (Cyramza) cost of treating per one patient is 1 761 564 RUB. From the perspective of relative value analysis the cost of an additional unit of effectiveness of ramucirumab is comparable or even lower than the same criteria of other antitumor drugs of monoclonal antibodies already included in the national EDL. Consequently, ramucirumab can be characterized as an acceptable technology. The budget impact analysis showed that providing patients with advanced gastric cancer with the ramucirumab is characterized by a lower burden on the drug support budget for oncological patients than bevacizumab, trastuzumab and cetuximab in the therapy of the oncology nosologies, at the their approval date. According to the results of the budget impact analysis on the drug supply of ramucirumab, 200 patients will additionally require 329.19 million rubles, which is only 0.64% of the budget for the treatment of cancer in 2016. Key words: gastric cancer, pharmacoeconomics, cost-effectiveness analysis, budget impact analysis, relative value analysis, bevacizumab, cetuximab, ramucirumab, trastuzumab.

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.

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.

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.

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.

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