Background. Systematic research work on the assessment of medicines consumption allows timely identification of effective and problematic aspects of the existing system of preferential medicines provision, allowing to regulate the optimality of its functioning. Aims to identify regional epidemiological features and key aspects of drug provision for patients with ankylosing spondylitis (AS) in Moscow in dynamics for the period 20172020. To identify the trend of changes and their specifics in order to optimize further preferential drug provision (DLO) for patients with AS in Moscow. Materials and methods. The sources of the study were the data of LLO of patients with AS within the outpatient care, registered in Moscow in 20172020. The researchers analyzed the number of patients with AS who are entitled to free and preferential drug provision, who received drugs as an outpatient link in the period 20172020. The age structure of beneficiaries with AS and their ratio by gender has been determined. A tendency was revealed in the distribution of patients according to the main drug therapy regimens, according to the drugs they received during the reporting period. The structure of LLO of patients with AS was revealed by international non-proprietary names of drugs, their dosage form, quantities, cost minus payment by patients. Results. A retrospective analysis of real-world data showed that the population with AS in Moscow increased by 1.5 times from 2017 to 2020, as well as the cost of expenses for LLO of these patients, excluding patient payments, also increased by 1.5 times. The average age of patients was 5014 years in 2017, and in 2018, 2019, and 2020. This indicator increased to 5111 years. The ratio of patients by sex was 2:1 male and female, respectively, in all periods studied. The maximum proportion of patients fell on the age group 4059 years, which was about 50% of the entire population of patients with AS during the entire study period. The second place was occupied by the age group 6079 years, which accounted for 28.10% of all patients with AS in 2017 and by 2020 decreased by 3.38%, already amounting to 24.72% of patients, the third place in the number of patients belongs to the age group 3039 years, which accounted for about 1718% of the entire population with AS during the entire study period. The analysis of the polypharmacy indicator indicates a low drug load of most patients since a small proportion of patients from 1.54% (20 people) to 2.71% (49 people) had more than 10 items for international nonproprietary names per year. The leading position was occupied by the therapeutic scheme of monotherapy NSAIDs in 2017, since 2018 the first place belongs to the scheme of therapy with one iTNF-. Conclusions. The increase in costs for the relief of adverse reactions and the treatment of concomitant diseases indicates a shift in the approach to the treatment of diseases of the musculoskeletal system, as pathologies accompanied by a wide variety of comorbid and polymorbid conditions. Despite the positive changes in the regional system of LLO of Moscow, it is possible to improve the indicators of the provision of patients with AS when evaluating its effectiveness, taking into account clinical indicators and the results of the assessment of the quality of life reported by patients.

Современная система отбора лекарственных препаратов для включения в федеральные ограничительные перечни (например, в перечень жизненно необходимых и важнейших лекарственных препаратов – ПЖНВЛП) становится все более совершенной. Внедрена комплексная шкальная оценка по критериям.В настоящей статье рассмотрены три шкалы, которые являются определяющими на этапе подготовки предложения для обсуждения вопроса о включении препарата в ПЖНВЛП: оценки качества клинических исследований, оценки экономических последствий применения лекарственного препарата и оценки прочих (дополнительных) данных.Для того чтобы набрать проходной балл, а также повысить общий балл по этим шкалам, возможны действия в следующих направлениях:•включение в предложение систематических обзоров, метаанализов и рандомизированных клинических исследований и исключение исследований типа «случай – контроль», когортного дизайна, описания клинических случаев или серии случаев, а также экспертного мнения;•при планировании и проведении клинико-экономических исследований и анализа влияния на бюджеты следует обращать внимание на выбор сравниваемого препарата, целевой популяции пациентов, критериев оценки эффективности, видов затрат и методов их учета, а также временного горизонта и метода моделирования;•локализация производства на территории России либо поддержка ведущих авторитетов по лечению болезней, включая главных внештатных специалистов Минздрава, считающих необходимым применение лекарственного препарата, в т. ч. в рамках стандартов оказания медицинской помощи и клинических рекомендаций.

INTRODUCTION:Liver cirrhosis is a major but preventable cause of health loss worldwide. The era of «big data» allows us to evaluate this nosology in a new format.PURPOSE:Evaluation of the registered population of patients with cirrhosis of the liver of cirrhosis of various etiology in Moscow. Moscow.MATERIALS AND METHODS:Based on the data of the Moscow Department of Healthcare for the drug provision for the period from 2017 to 2019. Тhe population of patients with an established diagnosis of liver (other etiology) was characterized according to ICD-10 code K.74 (K74.0-74.6) according to the International Statistical Classification of Diseases and Related Health Problems of the 10th revision.RESULTS:Over a 4-year period, more than 2 thousand patients with established diagnosis of liver cirrhosis received preferential drug provision in Moscow. The largest part of the population of patients with liver cirrhosis receiving preferential drug provision in Moscow is represented by the patients of age groups 40-59 years old and 60-79 years old, the groups 30-39 years old and 80-99 years old were comparable annually. There was a decrease in the number of patients with liver cirrhosis in the age groups of 30-39 and 18-19 years compared with the base year (2017) by 37% and 57%, respectively. At the same time, in pediatric patients (from the neonatal period to 17 years), there was an intensive increase in patients from 52 to 550% compared to the baseline year (2017).

Objective: to review the data on the efficacy and consumption of octocog alfa and rurioctoctog alfa pegol in standard prophylaxis and individualized prophylaxis in hemophilia A patients based on published international data. Material and methods: a systematic literature search and review were performed. Among 25 sources identified within the systematic search 7 relevant sources describing the comparison of treatment with octocog alfa and rurioctocog alfa pegol in adult and pediatric patients with severe and moderate hemophilia A based on personalized assessment of the pharmacokinetic curve using the interactive tool myPKFit versus the standard (non-personalized) dosage regimen were selected. Data on individual patients, as well as data from secondary subgroups defined by age, bleeding rate, risk of bleeding associated with the daily physical activity were combined and analyzed. Results. In observational studies, adjustments of the dose and administration of octocog alfa in patients with severe hemophilia based on personalized assessment of the pharmacokinetic curve using myPKFit resulted in the reduced consumption and/or increased efficacy of prophylaxis — a reduced annual bleeding rate. In an extended controlled study of rurioctocog alpha pegol a trend toward reduced bleeding rate and increased mean annual consumption of the drug was reported in patients who received myPKFit guided prophylaxis compared to a non-personalized treatment regimen. In the single-cut studies, myPKFiT use resulted in the regimen revisions in less than a quarter of patients. Summary. Personalized dosing for octocog alpha and rurioctocog alpha pegol based on pharmacokinetic curve built using pharmacokinetic population model enables reasonable dose adjustments and improves outcomes.

Interest in chloroquine, and its analog with a more favorable safety profile - hydroxychloroquine, in 2020 is certainly associated with the outbreak of a new coronavirus infection, SARS-CoV-2. The high pathogenicity and lack of specific immunity in the population caused the rapid spread of infection with an extraordinary increase in the burden on the health systems of many countries. In such conditions, it was necessary to quickly find and implement effective methods of treatment and prevention. One of the most promising candidates for this role was hydroxychloroquine, as a multi-purpose drug with a well-studied safety profile and a rich history of use. The article describes some historical stages of the study of chloroquine and its derivatives starting from the 19th century and ending in 2020. The experience of its use for the treatment of diseases such as malaria, rheumatoid arthritis, diabetes, bronchial asthma, photosensitivity and skin porphyria was reviewed. Separately, some historical aspects of its use for the treatment of viral and oncological diseases were considered. The bibliometric method used in this scientific work clearly demonstrates the dynamics of the changing interest of the scientific community in chloroquine and its derivatives. Chloroquine and its derivatives can definitely be attributed to «pharmaceutical centenarians» with an intense life that continues.

Objective : to determine the economic and clinical consequences of using atezolizumab in metastatic urothelial cancer compared with pembrolizumab and nivolumab. Materials and methods . An assessment of the effectiveness and safety of medicines for urothelial cancer was carried out on the basis of a systematic search and review of clinical studies and an analysis of direct medical costs for medicines from public procurement in Moscow in 2019-2020 and information from official instructions for medical use. Results . Systematic search identifies 4, 4 and 7 clinical trials of nivolumab, pembrolizumab and atezolizumab, respectively, as well as 2 meta-analyses. The obtained data on the efficacy and safety did not allow us to identify greater or lesser effective options. Calculation of cost of three months therapy revealed that the cost of atezolizumab (935 thousand rubles) is 7 % lower vs. pembrolizumab (1 million rubles) and 18 % lower vs. nivolumab (1,136 million rubles). Thus, when using atezolizumab instead of pembrolizumab or atezolizumab, budget savings may occur, or allowing additional therapy to be provided to every 14th or every 6th patient, respectively within fixed budget. Conclusion . The use of atezolizumab in metastatic urothelial cancer led to budget savings or the possibility of additional treatment coverage with immuno-oncological therapy.

The article presents a review of the historical facts related to the discovery and introduction of chloroquine and hydroxychloroquine. The history of studying aminoquinoline preparations is associated with the discovery of the antimalarial action of the bark of the quinine tree, the isolation of quinine from other active substances - alkaloids and the determination of their structure. The structural similarity of quinine and one of the first chemically synthesized dyes - methylene blue-was an important factor at the beginning of the synthesis of molecules with antimalarial activity in the 1930s in Germany. Pamaquin (plasmoquin, plasmoсid), quinacrine (quinacrine, Atebrin, Mepacrine), sontoquine (sontochin), chloroquine, primaquine, hydroxychloroquine, and mefloquine (Lariam) were consistently introduced in medical practice. Many of these medications are no longer widely used. However, chloroquine and hydroxychloroquine have not lost their relevance. The scope of their use has been expanded.

To find a method for preliminary HTA of therapeutically similar medicines (used in the same clinical situations with similar efficacy and safety) in the basis of criteria ranking in the low or middle decision-making level (e.g. in a city or hospital). We were searching for solution for the resource- and time-saving approach to the question of priority setting in therapeutically similar medicines (e.g. modern medicines for rheumatoid arthritis, severe asthma, diabetes, multiple sclerosis, and viral hepatitis). Then, we described and compared the methods. We found and considered three methods: ranking rows constructions (RaRos), Interval Distribution (InDis), and Proportional Scaling (ProSca). RaRos means ranking of each criterion value from best to worst and then putting the ranks together. If one medicine has preferable ranks than another then it should be the drug of choice. RaRos method helps to underline small differences, but neglects volume of differences. InDis (e.g. quartile distribution) means the spread of each criterion value in the fixed number of intervals (e.g. four intervals in quartile distribution). This method seems vaguer than the other ones. ProSca means placement of the criteria values in the fixed scale from 0 to 1, 10, or 100 by using proportional interpolation (minimal criteria value ∼ 0 and maximal ∼ 1). To compute average mean value we need to determine relative weights of each criterion. ProSca is more précised but more time and resource consuming method. All three methods allowed comparing different criteria within time and resources constrains. In some cases, preliminary assessment can be enough to make decision on a local level. RaRos method is one of the favorable preliminary HTA methods, which allow making a decision whether one medicine would dominate over another or whether next level of HTA is strictly required.

This article presents the results obtained during the analysis of different types of health technology assessment (HTA). In the world HTA agencies can be organized at the national (federal), regional or local levels; they can have various levels of dependence on public authorities (independent, public, dependent), various sources of financing (state, mixed). The nature of the tasks and the range of powers of the institutions for HTA differ: regulatory, organizational or advisory. They themselves can initiate HTA (proactive), or they can conduct HTA at the suggestion of the applicants and analyze the quality of the HTA reports provided (reactively). HTA can be focused on economic assessment, comparative clinical assessment, as well as balanced, both on economic and comparative clinical assessments. HTA may be conducted on drugs, medical devices, and other medical technologies. The methods for conducting HTA significantly depend on its subject. In terms of the scope of the assessment, it is possible to single out full OMT, mini-OMT and express-OMT, as well as fast-track-OMT, proposed by the HTA agency in the UK. The final users of HTA (administration, suppliers, patients) and its perceptions (instrumental, conceptual, or formal) are specified. The impact of HTA on decision-making is progressively increasing, as the number of medical technologies that should be assessed to maintain budget discipline is increasing. The versatility of HTA indicates its universality and can contribute to the further expansion of its application at various levels of medical care around the world.

Over the past few years, risk-sharing schemes have gained a significant position in drug supply in developed and developing countries. In the Russian Federation, the introduction of innovative drug supply models (IDSM) has been underway for the past few years. Aim of the study is presentation of the algorithm for developing the necessary documents for the introduction of risk-sharing schemes in today's Russian legal environment. The analysis of foreign and Russian scientific literature, Russian federal and regional legal acts was conducted in the search for existing innovative schemes for providing patients with the necessary medical technologies that have issues about their effectiveness and / or their costs. As a result of the analysis, it was found that currently there is no officially approved algorithm for the implementation of risk-sharing schemes in Russia, and also to organize and conduct a valid IDSM, the following documents will need to be developed: agreement, requirements for the formation of a patient register, the form of inclusion in patient register, performance evaluation procedure, product specifications, invoice, acceptance report, delivery notes, and software for monitoring the results of IDSM (in the case of pay for result type of agreement). Documentary support for conducting IDSM in the Russian Federation is a task requiring serious legal support.

Objective. To determine the consequences of the use of a fi xed combination of solifenacin and tamsulosin in patients whom recommended the prescription of these drugs. Methods. Analysis of prices of drugs solifenacin + tamsulosin controlled release (Vasomni), solifenacin (Vesicare), tamsulosin controlled release (Omnic Okas) and tamsulosin modifi ed-release (several registered trade names of the drug) conducted on the basis of information from several sources: 1 — the register of maximum ex-works prices of manufacturers of vital and essential medicines, 2 — data on average prices in pharmacies of Moscow (as of 15.02.2018), 3 — weighted average prices of public procurement for 2018 according to the monitoring of the pharmaceutical market. To determine the points of relative value of drugs, a survey of experts was conducted: 1 — to determine the values of the criteria for the drugs under consideration — urologists; 2 — to determine the weight of the criteria — persons involved in the decision-making on the selection and purchase of drugs. Results. We found that the cost of the equivalent course dose of Vesomni was on 40-42 % lower than the combination of drugs Vesicar and Omnik Okas. Compared with the non-fi xed combination of solifenacin with tamsulosin in a drug form with modifi ed release, no signifi cant diff erences in price levels were found. At the same time, the relative value of a fi xed combination is 5-6 percentage points higher compared to non-fi xed combinations, mainly due to ease of use. Conclusion. Use of a fi xed combination of solifenacin + tamsulosin can lead to budget savings with an increase in the level of relative value.

To determine short-term financial consequences of the use of mepolizumab in severe eosinophilic asthma (SEA) versus omalizumab and reslizumab where the comparison is reliable. Assessment of clinical outcomes was based on published meta-analyses. Cost-minimization and budget impact analyses were performed from healthcare perspective and one year time horizon. Targeted populations included adult severe eosinophilic asthma patients with elevated IgE level, and weight ranged 66,6 - 100 kg. We collated only annual drug costs. Dosages were derived from the labels. We used prices data from different sources (incl. tender-auction, retail and registered prices). Exchange rate: €1 = 73,26 rubles (as of 10/06/2019; available at www.cbr.ru). Deterministic one-way sensitivity analysis was performed. Based on meta-analyses (Cockle 2016, Henriksen 2018) we assumed the same efficacy and safety. Annual treatment cost of mepolizumab, reslizumab, and omalizumab were €11425, €13461, and €22043, respectively. Therefore, budget savings when using mepolizumab amounted to €2036 versus reslizumab, and €10618 versus omalizumab per patient per year. Results can be sensitive to price fluctuations. Once the price landscape will change the results should be recalculated. Mepolizumab can be cost-saving alternative versus reslizumab and omalizumab in the specified population of eligible patients with severe eosinophilic asthma.

The aim is to develop a generalized algorithm and methodology for conducting clinical and economic studies (CeS) on medications used in treatment of malignant neoplasms (MnP). Materials and methods. We conducted a literature search and then reviewed the recent reports on similar CeS. In so doing, we paid special attention to the model type, the modeling methodology, information on the effectiveness and cost, the cost elements, performance criteria, the assessment of the CeS final results, as well as the possibility of applying these results to the national healthcare system. We used the methods of generalization, systematization, as well as visual-graphical and mathematical modeling. Results. A general algorithm for conducting a pharmacoeconomic study has been proposed; this includes an effectiveness analysis, a cost analysis and a comparison of costs and effectiveness (cost-effectiveness). The effectiveness analysis includes selection, digitization, and approximation of overall survival (OS) and progression-free survival (PFS) curves followed by their extrapolation. The choice of extrapolation method is discussed. The cost analysis includes calculating the cost of medications in question, the costs associated with the indicated therapy and with adverse events (Ae), as well the costs associated with disease progression (for certain drugs). The possibility of analyzing indirect and non-medical costs is also discussed. A dynamic version of the Markov model pertaining to the first order course of a disease is proposed; this includes the status before progression (first-line therapy), after progression (second-line therapy) and death. Considering the succession of treatments and the availability of additional data, a similar second-order model (and subsequent orders) can be applied to incorporate additional patient’s condition after the first progression to the second progression (second-line therapy) and after the second progression (third-line therapy). Conclusion. A generalized algorithm has been developed and proposed for carrying out CeS of medications used in MnP.

Objective. To determine the clinical and economic consequences of the drug mepolizumab in patients with severe bronchial asthma (SBA) and the ineff ectiveness of omalizumab. Methods. We conducted cost-eff ectiveness and budget impact analysis of the use of mepolizumab or omalizumab in omalizumab-refractory patients with SBA. Source of information about the eff ectiveness were the results of published clinical studies; the cost of drugs — maximum ex-works prices of manufacturers of vital and essential medicinal products and instructions for use of drugs; the cost of medical services — program of state guarantees of free medical assistance on the territory of the Russian Federation, as well as the coeffi cients of relative cost intensity for clinicalstatistical groups. Results. According to the results of a multicenter open study OSMO, the use of mepolizumab in patients with ineff ective omalizumab therapy led to a decrease in the frequency of clinically signifi cant exacerbations and exacerbations requiring hospitalization (1.18 and 0.19 cases / year, respectively) compared to 12 months before screening (3.26 and 0.63 events / year, respectively). Result of the cost analysis showed that switching to mepolizumab leads to signifi cant savings: the sum of direct medical costs was 865 217 and 1 666 401 RUB per patient per year, respectively. Budget impact analysis demonstrated savings in the CHI system in the treatment with mepolizumab within the analyzed cohort of patients (n=18) by 2.8 million rubles in the fi rst year and 12.7 million rubles in 5 years. Analysis of «missed opportunities» showed that the use of mepolizumab can allow to treat an additional 3 people for 1 year of therapy and 15 people for fi ve years of implementation of the analyzed drug. Conclusion. The use of mepolizumab in patients with SBA resistant to omalizumab, will reduce budget costs and will increase the eff ectiveness of treatment.

To pilot a questionnaire on weights of medicines’ value criteria, and understand which improvements are needed? We developed a questionnaire which included 5 questions about the value of medicines themselves: 1. Influence to survival, 2. Influence to quality of life (QoL), 3. Safety, 4. Usability, 5. Prevention of costs in future; 5 questions about the importance of targeted patients’ population: 1. Prevalence/incidence, 2. Mortality, 3. Availability of treatment options, 4. Age, 5. Burden for society; And 7 questions for expertise adjustments about a level and role of respondent in decision-making. Survey was conducted as anonymous written form fulfillment. Each criterion was proposed to be evaluated in a visual scale from 1 to 10 where 1- not important, and 10 – crucially important for decision making. We calculated weighted average and standard deviation (SD). We collected fulfilled forms from 15 employee of The HTA Center of Moscow healthcare department. The most important value factor was influence to survival (9.5 SD1.00), then safety (9.25 SD0.96), cost prevention (8.5 SD1.91), influence to QoL (8.25 SD2), and usability (4.5 SD1.29). Patients’ population factors has next weights: mortality (9.0 SD0.82) and treatment options availability (9.0 SD2), then prevalence (8.3 SD1.26), burden (8 SD1.41), and age (6.5 SD3.11). The results are only approbation of the questionnaire and then should be interpreted carefully because of small sample size and one-sided respondents. To reduce deviations in responses it is needed to reformulate questions about target population importance, as well as specify scales ranges for all criteria. Current version of the questionnaire can be used in a value of medicines assessment. The mentioned improvements can make the questionnaire more accurate and precise. The questionnaire is an obligatory part of a tool for substantiated value-based decision-making in healthcare.

To determine key factors for therapeutically similar medicines (TSM) differentiation and solutions for interpretation of controversial cost-effectiveness results. We analyzed results, authors’ conclusions, criteria and other in-depth details (where available) of local (Russian) cost-effectiveness analyses (CEA) of next TSM: 1) iDPP-4 in diabetes mellitus type II: alogliptin, linagliptin, saxagliptin, sitagliptin, and vildagliptin; 2) LABA+ICS in bronchial asthma: formoterol+budesonide (For+Bud), salmeterol+fluticasone propionate (Sal+FP), Formoterol+Beclomethasone (For+Bec) and vilanterol+fluticasone furoate (Vil+FF); 3) BRAF-inhibitors in metastatic melanoma: dabrafenib and vemurafenib. 1) One CEA demonstrated advantage of saxagliptine over sitagliptine and vildagliptine by cost per case of normoglycemia (ArininaEE 2012). Two CEAs demonstrated domination of alogliptine over other iDPP-4 by cost of drugs (SabanovAV 2015) and cost per QALY (NedogodaSV 2015). These CEAs contradicted in the place of Linagliptine: 2nd in Sabanov and 4th in Nedogoda research. Recent CEA (KulikovAU 2018) showed vildagliptine predominated over alogliptine by cost per life year gained. 2) Sal+FP versus For+Bec and For+Bud had minimal cost per QALY, but authors concluded priority of For+Bec (KulikovAU 2017). Two another CEA are both stated advantage of Vil+FF over Bud+Form by cost per QALY (Kulikov AU 2018) and cost of drugs (PogudinaNL 2017). CEA of LABA+ICS were enough consistent. 3) Results of two local CE analysis of Dabrafenib and Vemurafenib completely contradict each other in spite of the same criterion (direct medical cost; KulikovAU 2016; KolbinAS 2017). In-depth analysis of the CEAs of TSM found: clinical outcomes varied in the narrow limit (±5%) and often ambiguous; cost of medicines varied more widely (±10-30%) and was determining factor of CEA results. Key factor for TSM differentiation is drug prices. Interpretation of diverse CEA of TSM may base on actual cost per drug comparison.

Objective: Based on the cost-effectiveness analysis (CEA) to determine economic and clinical consequences of using mepolizumab instead of omalizumab in adults with severe eosinophilic asthma, when omalizumab is administered once every 2 weeks or mepolizumab is administered once every 4 weeks. Methods: Effectiveness and safety analysis was conducted based on the published network meta-analysis, because head-to-head clinical trials of omalizumab versus mepolizumab were not identified during targeted scientific literature search. Direct medical costs were calculated using information from the register of manufacturers` maximum selling prices for vital and essential drugs (VED), instructions for medical use, the unit cost of healthcare services. Results: Effectiveness and safety of the compared drugs were determined based on the results of the network meta-analysis. Frequency of clinically significant asthma exacerbations (risk ratio = 0,19; 95% CI: 0,02–2,32) and withdrawals due to adverse events (risk ratio = 0,05; 95% CI: 0,002–0,95). Therefore, despite the tendency to mepolisumab benefits, it was concluded that there are no statistically significant differences in the effectiveness and safety of the compared drugs due to the insufficient statistical power of the result. Direct medical costs were 870130 rubles and 1852063 rubles for mepolizumab and omalizumab respectively. Saving of direct medical costs for mepolizumab treatment was 959170 rubles per patient per year or 52%. Conclusion: treatment with mepolizumab versus omalizumab in patients with severe eosinophilic asthma, when omalizumab is administered once every 2 weeks or mepolizumab is administered once every 4 weeks, leads to saving of direct medical costs for drug treatment.