Serpik Vjacheslav Gennadievich

The limited financing of the program of pharmacological support of high-cost nosologies emphasizes the importance of more effective use of the available resources. In order to improve the efficiency of use of the available resources of pharmacological support of inhibitor hemophilia patients receiving therapy in the prophylactic regimen, a budget impact analysis of prophylactic treatment by BPA anti-inhibitor coagulant complex and eptacog alfa [activated] was performed. In accordance with the instructions for use of eptacog alfa, this medicinal product is not indicated for long-term preventive treatment of bleedings, however, as eptacog alfa is used in the said regimen, it was included in the analysis. The analysis horizon period made 1 year and 75 patients were included in the analysis. The analysis shows that prophylactic anti-inhibitor coagulant complex therapy offers better control over the disease and reduces the costs. The incidence of bleedings in prophylactic anti-inhibitor coagulant complex therapy is reduced by 72.5%, while the incidence of bleedings in prophylactic treatment by eptacog alfa is reduced by 59% as compared to on demand therapy. The annual costs of prophylactic anti-inhibitor coagulant complex therapy per patient make 58.8 million rub (per adult patient) and 23.5 million rub (per pediatric patient), while the annual costs of bleeding prophylactic eptacog alfa treatment proved to be higher by 37.4% and made 94 million rub per adult patient and 37.6 million rub for pediatric patient. Transfer of all patients who respond to anti-inhibitor coagulant complex therapy and receive therapy with this medicinal product in prophylaxis regimen will save 765 million rub or 17.3% of the budget, provided that the current distribution of patients is preserved. Thus, the budget impact analysis demonstrates that the transfer of patients receiving therapy with eptacog alfa in prophylaxis regimen to AICC will improve the control over disease and save the budget funds under the 7N Program.

With its high disability and severity, Crohn’s disease (CD) is a serious socio- economic burden for both the patient and society as a whole. Therefore, the choice of a therapy strategy for CD should be aimed not only at controlling the disease but also at the rational allocation of resources in health care system. Taking into account the appearance of innovative biologic drugs (biologics) that offer additional options for the treatment of the CD with new data from clinical studies, the decrease of registered maximal selling prices, the development and output of biological analogues (biosimilars) as well as taking into account the limited budget of the health care system, it became obvious that it is necessary to update the pharmacoeconomic evaluation of biologics in CD therapy. The purpose of this study was to evaluate the introduction of ustekinumab drug into clinical practice of CD therapy basing on cost analysis, cost-effectiveness analysis and budget impact analysis in comparison with alternative biologics. The study found that the sum of costs for the use of ustekinumab in the regimen of 1 injection at 12 weeks was the lowest among vedolizumab, adalimumab and infliximab biosimilars and comparable in costs among adalimumab, infliximab and certolizumab pegol. The cost-effectiveness analysis showed that treatment of CD with ustekinumab is characterized by lower costs per effectiveness unit (share of patients who achieved a CDAI-100 response, share of patients who achieved a CDAI remission of <150, and QALY) in a 1/12 weeks dosing regimen compared to all other biologics and in the 1/8 weeks dosing regimen among infliximab biosimilars; in the first year of therapy ustekinumab is also a “cost-effectiveness” technology compared to vedolizumab. Switching of 15% of patients to ustekinumab (1/12) is characterized by budget slight increase in costs within the ONLS and RLO financing channels for the 1st year and three years of therapy. Within the OMI system there is a decrease in costs allocated by the OMI Fund for a treatment facility and there is a decrease in the difference between the amount of payment received by a treatment facility for cases with the use of biologics and the cost of purchasing biologics. As a result of the study, the introduction of ustekinumab in clinical practice is justified from the pharmacoeconomics point of view.

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.

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.

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 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.

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.

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.

In recent years, due to the widespread use of pharmacoeconomic modeling for economic and decision analysis, the variety of pharmacoeconomic models has significantly increased, which from the point of view of methodology actualizes the problem of their systematization. The first step in solving this problem is to identify the key principles of a possible classification, for which, in turn, it is necessary to highlight and describe the interaction of the attributes of pharmacoeconomic models. In this article, the authors highlighted, grouped, and described 26 attributes of pharmacoeconomic models.

Pharmacoeconomic assessment is an obligate element for including a drug in the reimbursement lists – EDL and state federal reimbursement drug list, which in turn represents an important step in ensuring the availability of drug therapy. In this regard, the registration of a new drug of the group of janus kinase inhibitors, baricitinib in Russia, used in the treatment of rheumatoid arthritis in patients with moderate and severe degree of intolerance or lack of adequate treatment for one or more basic antirheumatic drugs, actualized the task of its pharmacoeconomic assessment. The pharmacoeconomic analysis of baricitinib by the cost-effectiveness methods compared with adalimumab and the “budget impact” compared with the entire group of genetically engineered biological products showed that, from the point of view of the cost-effectiveness evaluation, baricitinib is characterized as a dominant alternative, and with the position of the “budget impact” evaluation, the use of baricitinib is accompanied by budget savings. In accordance with the current rules of pharmacoeconomic assessment, the drug baricitinib gains + 9 points and, by decision of the Commission of Ministry of Health, was included in the lists of EDL and state federal reimbursement drug list, approved by Order of the Government of the Russian Federation 2406-R of October 12, 2019.

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).

This article discusses the issues of pharmacoeconomic modeling related to the description of the movement of patients in the pharmacoeconomic model, as well as approaches to determining the course dose of drugs under the condition of integer calculations. In particular, we described two possible ways of distributing patients between treatment regimens in pharmacoeconomic models, also analyzed the effects of simultaneous and uniform entry of patients into the model. As part of the issue of determining the course dose of a drug, we described the limitations and possibilities of calculations based on the active substance and packaging, as well as the transition factor of the remainder of the drug in the next time period.

Budget impact analysis of treatment of ankylosing spondylitis was carried out on the for cohort of 100 patients in the Russian Federation. With the current distribution of patients, adalimumab received 26%, golimumab – 14%, infliximab – 26%, etanercept 18%, certolizumab pegol 7%, secukinumab – 9%. With the simulated distribution of patients, the share of the most economical drug, secukinumab, was increased to 21.8%, while the shares of adalimumab, golimumab, infliximab, certolizumab pegol and etanercept were 21.6%, 13.8%, 13.8%, 5, 8%, 13.8%, respectively. Also, in the simulated distribution, the shares of recently registered drugs – netakimab - 6.8%, and ixekizumab – 2.6% were taken into account. With the current distribution of patients between drugs the budget is 92,868,680 rubles in the first year and 258,825,970 rubles for three years. With a simulated distribution, the costs in the first year are 86,626,248 rubles and 240,444,152 rubles for three years. Thus, when calculating per 100 patients, the simulated distribution of patients in comparison with the current one provides savings in the amount of 6,242,431 rubles in the first year and 18 381 818 rubles for three years. With the saved money, 9 patients can be additionally treated with secukinumab.

Aim: to conduct a comparative assessment of the efficacy and safety of ERT drugs in MPS II type patients and analyze drug provision organization for pa- tients with this nosology. Methods: to conduct a comparative assessment of the efficacy and safety of ERT drugs, clinical trials data and real clinical practice data, including data from the Hunter outcomes survey register, were used. To assess the drug pro- vision organization were analyzed the current legal framework of the Russian Federation and public procurement data. Results and discussions: provision of pathogenetic therapy to the patients with orphan diseases is attributed to a number of administrative, clinical and eco- nomic constraints. The best example of the management of provision of this patients in Russia is a so-called Federal Program of High-cost nosologies (HCN) that has clear and transparent state regulation and the patient register that is essential for budget planning. The example of mucopolysaccharidosis type II (MPS II) that was included in HCN in 2019 shows noticeable increase in pa- tients’ access to therapy when transferring from regional budgets. Two medical products – idursulfase and idursulfase beta – are available in Russia for life-time pathogenetic treatment of this nosology. These products are produced using different cell lines; they have different INNs and are not interchangeable. Both drugs have registration clinical research, however, unique real world evidence is available for idursulfase only and show the survival rate of the patients with MPS II collected during 15 years of maintaining the international patient register cov- ering more than 1,000 patients from 129 countries, including Russia. According to the analysis, mortality risk in the patients treated with idursulfase is lower by 54% than in those who received no treatment (HR 0.46, 95% CI: 0.29; 0.72). This evidence can be used by health care decision makers to prioritize value of this medicinal product from both clinical and pharmacoeconomic perspectives. Predictability of therapy outcomes and higher prescription frequency according to current standards of care justifies idursulfase as a first choice treatment.

The presence in Russia of legally approved rules for the pharmacoeconomic assessment of drugs when considering their inclusion in the lists of vital and essential drugs (reimbursement), as well as in the list of medical nutrition for children with disabilities, has features of pharmacoeconomic analysis of parenteral and enteral nutrition. Since parenteral and enteral nutrition can have different legal status - a drug (MP), biologically active additive (BAA) and even medical products, the rules for pharmacoeconomic assessment at the federal level will be different for them.

The article describes the principles of the international classification of rare diseases, proposed by the organization Orphanet. The supranosological nature of rare diseases predetermined the task of developing their new classification, which is more convenient for coding in the framework of their treatment than ICD-11, but coordinated with it. For these purposes, the international organi- zation Orphanet, formed in France in 1997, together with WHO, is developing an additional classification of rare diseases with the assignment of each noso- logical unit its own unique code based on the collection of information and the formation of its own database of their nomenclature. The Orphanet nomencla- ture includes the following elements: a unique Orpha disease code, a common or most common disease name, synonymous disease names, keywords often used to search for a given disease, if any, and the disease definition itself.

The global pharmacoeconomic model of cost-effectiveness analysis of insulin degludec (Tresiba®) use in comparison with insulin glargine U300 in the treatment of type 2 diabetes mellitus, was validated. As the result, it was found that the model is relevant to local clinical practice, fully complies with the pharmacoeconomics methodology, takes into account the entire spectrum of costs relevant for the pharmacoeconomic evaluation of insulin in Russia, and the computations built in it is correct. Based on the actual cost data entered, the model calculated the ICER of degludec insulin, which was 214,714 rubles, which does not exceed the sum of three GDP per capita – 2,184,562 rubles and corresponds to the willingness to pay threshold in the Russian Federation. Thus, the insulin degludec (Tresiba®) can be considered as cost-effective from the standpoint of the conducted pharmacoeconomic analysis.

We conducted an budget impact analysis was made of the treatment of spinal muscular atrophy (SMA) with drugs Nusinersen and Risdiplam. Its results showed that from the point of view of the organization of drug provision for patients with SMA at current prices, treatment of patients under 18 years of age within the framework of the responsibility of the Circle of Kindness Foundation, given the current distribution of patients, in which 57.6% receive Nusinersen, and 42.4% Risdiplam, is characterized by a smaller budget already in the first year – 18.82 billion rubles, in comparison with the budget of the simulated distribution, in which 42.4% of patients receive Nusinersen, and 57.6% of Risdiplam – 19.27 billion rubles. Thus, with the current distribution over 5 years, budget savings in comparison with the simulated distribution reaches 3.24 billion rubles, excluding the discount factor, and 2.86 billion rubles, when discounting. Analyzing the long-term effect of the budget impact of the use of Nusinersen drugs per patient at the beginning of therapy at the age of two months, it was found that the total savings before the patient switches to provision through regional funding (reaching 18 years of age) can reach 59.72 million. rub. From the point of view of drug provision for patients with SMA at the regional level, that is, patients over 18 years old, the main pool of patients will be formed due to the successive transfer of patients from the Circle of Kindness Fund, since most of the patients (1039 people) are now provided precisely for the account of the Circle of Kindness Fund, and upon reaching the age of 18, this cohort of patients will be transferred to provision at the expense of the budgets of the regions of the Russian Federation. At the same time, it is noted that the costs of initiation of these patients with Nusinersen were covered by the Circle of Kindness Foundation, and therefore, from the point of view of the regions of the Russian Federation, savings on Nusinersen in comparison with Risdiplam will be noted already in the first year of therapy, based on the fact that the annual costs for Nusinersen maintenance mode are 16,957,680 rubles. per patient, and the annual cost of treatment with Risdiplam drug for one adult patient (weighing more than 20 kg) exceeds 20 million rubles. Thus, the stated results of the budget impact analysis revealed the economic feasibility of Nusinersen in the treatment of SMA in comparison with the Risdiplam.

In order to preserve the health of elderly patients, methodological approach- es to the pharmacoeconomic substantiation of the inclusion of drugs for the treatment of dyslipidemia in the list of vital and essential drugs (EDL) were adapted and an appropriate assessment of the drug of cholesterol absorption inhibition was carried out, which showed that from the point of view of the healthcare system, the presence of this drug in the list will have a positive effect: Impact on the budget by increasing the availability of this drug for patients and delaying the prescription of expensive drugs of the PCSK9 inhibitor class. From a clinical point of view, increasing the availability of cholesterol absorption inhibition drugs for patients when it is included in the list of essential drugs will ensure that the correct sequence of the therapeutic line is followed in the treatment of dyslipidemia.