Objective. To determine the pharmacoeconomical feasibility of using a combination of atezolizumab + nab-paclitaxel in the 1st line of therapy for locally advanced or metastatic triple negative breast cancer (TNBC) in adult PDL1 positive patients in the Russian healthcare system. Materials and methods. A decision analysis model was used followed by Markov modelling for the economic evaluation of the drugs in the treatment of metastatic TNBC. We used the «cost-effectiveness» analysis and the «impact on the budget» (BIA) analysis. Two therapeutic approaches were evaluated: the use of combined therapy with atezolizumab + nab-paclitaxel and monotherapy with nab-paclitaxel. The analysis included direct costs. Additionally, the obtained pharmacoeconomical indicators of the use of a combination of atezolizumab and nab-paclitaxel and other drugs for the treatment of locally advanced and metastatic breast cancer were compared. Results. The use of the estimated therapeutic approaches in the treatment of metastatic TNBC was characterized by the following costs: with a modelling horizon of 1 year, the cost of using atezolizumab in combination with nab-paclitaxel was 5,076,321 rubles per patient. The costs for the use of single agent nab-paclitaxel with was 60 % less than: — 2 020 038,78 RUB. At the same time, the effectiveness of therapy with a combination of atezolizumab and nab-paclitaxel clinically significantly exceeded that of nab-paclitaxel monotherapy: a 38 % reduction in the risk of death or progression, a 10-fold increase in the frequency of complete response to therapy (10 vs 1 %), and a 7-month increase in the median overall survival (25 vs 18 months). The economic evaluation of the combination of atezolizumab with nab-paclitaxel was carried out with the calculation of the incremental cost-effectiveness ratios (ICER) — the calculation of the additional cost for each additional year of life in comparison with standard therapy. Due to the fact that currently in Russia for patients with metastatic TNBC no similar performance modes of therapy ICER for the combination atezolizumab + nab-paclitaxel compared with the ICER for palbociclib in combination with fulvestrant (drugs, showed improved overall survival in clinical research and included in clinical guidelines for the treatment of diseases of the same class ICD-10 in locally advanced and metastatic breast cancer). The ICER for overall survival at the end of the first year of follow-up for atezolizumab + nab-paclitaxel and palbociclib + fulvestrant was 30.5 million rubles and 47.4 million rubles, respectively. For the combination of atezolizumab + nab-paclitaxel, ICER is lower than the similar ICER for the palbociclib + fulvestrant mode by 36 %. Analysis of trends in the weighted average cost of systemic pathogenetic treatment of breast cancer (breast cancer) shows the following: increased use of the combination of atezolizumab + nab-paclitaxel for the treatment of patients with metastatic TNBC doesn’t lead to a considerable growth in the cost of therapy in patients with breast cancer — providing therapy to 1400 patients that includes the entire target population of patients with TNBC and expression of PD-L1 in Russia changes in the costs of chemotherapy and immunotherapy of breast cancer will remain within 2.6 %. Conclusion. Pharmacoeconomic indicators of the use of atezolizumab in combination with nab-paclitaxel are more cost-effective in comparison with other expensive schemes for the treatment of breast cancer, and tumors of other localities that are actively used in current practice, which suggests the acceptability and feasibility of introducing and expanding the use of this therapeutic option in the target population.

Rationale. Rheumatoid arthritis (RA) and systemic juvenile arthritis (sJA) are the most frequent rheumatic diseases in adults and adolescents, consequently. Biologics disease modifying antirheumatic drugs (bDMARDs) are eff ective in treatment of RA and s JA. Aim. To perform health-economic analysis of tocilizumab for subcutaneous and intravenous injections in patients with RA and sJA comparing to TNF-α inhibitors. Materials and methods. Cost-minimizing analysis was used from the perspective of healthcare system (accounting for direct medical costs) with the modelling horizon — 1 year. We included into the model cost of RA and sJA bDMARDs, cost of adverse events correction and costs of laboratory and instrumental diagnostic. Results. Cost minimizing ratio of tocilizumab (subcutaneous form) in RA patients comparing to adalimumab (Humira), сertolizumab pegol, golimumab were 111 536; 129 094; 85 244 RUR, consequently favour to tocilizumab. Tocilizumab was less costly comparing to adalimumab (Humira), certolizumab pegol, golimumab by 12.8, 14.5, 10,0 %, consequently. Cost minimizing ratio of tocilizumab in RA patients comparing to adalimumab (Dalibra), etanercept, infl iximab (Remicade) were 40 497; 54 355; 28 419 RUR in favour to comparators. Tocilizumab was more costly comparing to adalimumab (Dalibra) etanercept, infl iximab (Remicade) by 5.6; 7.7; 3.9 %, consequently. Cost minimizing ratio of tocilizumab in sJA patients comparing to kanakinumab, adalimumab (Humira) and adalimumab (Dalibra) were 6 535 234; 478 297 and 323 263 RUR. Tocilizumab was less costly comparing to kanakinumab, adalimumab (Humira) and adalimumab (Dalibra) by 93.3; 50.6 and 41.1 %, consequently. Conclusions. Tocilizumab is economically reasonable comparing to others TNF-α inhibitors in patients with RA and sJA.

Purpose. Assessment of the socio-economic burden of COVID-19 in the Russian Federation (RF). Materials and methods. Identification and assessment of direct medical, direct non-medical costs, as well as indirect costs associated with the development of the coronavirus infection epidemic. When calculating the socio-economic burden, the prevalence-based calculation approach was chosen. The sources of data on the epidemiology of the disease were data from the Ministry of Health and data from the Government of the Russian Federation. Results. The socio-economic burden of COVID-19 in the Russian Federation will amount to 4.6 trillion rubles ($71.1 billion) or 4 % from GDP. In the cost structure, more than half of the costs are direct non-medical expenses (58.62 %), indirect expenses due to GDP losses are 40.65 %, direct medical expenses are only less than 1 % (0.74 %). The results of the sensitivity analysis showed that the extension of the self-isolation period from 1 month to 1.5 and 2 months will lead to an increase in the share of indirect expenses from 40.65 % (1 month) to 56.08 (1.5 months) and 67.76 % (2 months) for all expenses in connection with the COVID-19 epidemic. At the same time, the socio-economic burden of COVID-19 will amount to 6.2 and 8.5 trillion rubles, respectively. Conclusions. The epidemic of a novel coronavirus infection will lead to great economic losses in the Russian society.

Improving the quality of drugs is the main task of the pharmaceutical industry as a whole. Getting safe and eff ective medications is directly related to minimizing the risks of conducting clinical trials. Maintaining the quality of clinical research based on risk management is a continuous, constant and dynamic process ensuring the success of the study, which in turn leads to the integrity of the data collected, the safety of subjects and compliance with legal requirements, as well as to the financial cost savings of pharmaceutical companies. The cost of research is growing inexorably, and the quality of their research is rapidly declining, so it is important to use a risk-based approach when developing the upcoming clinical trial project.

Objectives. Obesity is a chronic relapsing disease that requires long-term and lifelong treatment. The development of diseases associated with obesity may cause the additional need for prescribing drug therapy. The main aim was to analyze the structure of preferential drug prescriptions for patients with obesity for the period 2015-2018 in Moscow. Methods. A pharmacoepidemiological retrospective analysis of the structure of drug prescriptions for the period 2015-2018 in Moscow according to the chosen nosology — obesity (code ICD-10 — E66) was performed. The total number of patients receiving medications, the total number of prescribed prescriptions and packages were analyzed. The results are processed using the MS Excel 2013 package and are presented in the form of absolute values, shares (%). Results. For the period from 2015-2018 there is a 3.5-fold increase in the number of obese patients receiving preferential drugs — from 259 people up to 899 people. Over the entire analyzed period, there is a gradual increase in the proportion of drugs for the treatment of diabetes (from 43.1 to 51.6 %), mainly due to metformin, and for the treatment of the gastrointestinal tract (from 6.7 to 18.7 %). The total costs of drug therapy for obese patients over the analyzed period increased by 3.6 times. The largest share of the costs was attributed to drugs for the treatment of diabetes mellitus (from 38.1 to 62.5 %). Conclusions. Analysis can help to improve the system of rational distribution of financial resources for the drug provision of obese patients through the development of clinical and economic approaches that allow choosing the most effective and less costly approaches to providing medical care to patients.

Conducting of clinical trials is closely associated with the ethical justification, with ensuring the rights and safety of the subjects participating in them. Only through trials, it becomes possible to obtain reliable data for the inclusion of new drugs in practice, which are designed to save millions of lives. In the constantly developing field of clinical research, science does not stand still and it becomes necessary to conduct more and more new research: pediatric, geriatric, biomedical products and research involving acute social problems, and of course they all involve certain risks during their implementation. The question of the ethics of conducting research in the context of the COVID-19 pandemic is very relevant at the moment, when it is necessary to make quick decisions in the interests of all mankind, assessing all possible risks that they may entail.

In last years, special attention has been paid in the Russian Federation (RF) to improving medical care for patients with atrial fibrillation (AF) and the prevention of thromboembolic complications (TEC). The appearance on the Russian market of new oral anticoagulants (NOAC) has become a help for doctors, however, their cost imposes restrictions on the use. A humanitarian aid drugs to medical organizations of the RF, an active information program from manufacturers over the past 1.5 years have significantly increased the use of NOAC. In different regions, a different situation arises regarding the procurement and frequency of use of one or another anticoagulant. Analyzing the procurement of additional drug supplies for different regions of the Russian Federation, we see that dabigatran is preferred in a number of regions of the Central Federal District, and rivaroxaban in the Northern regions. The cost of warfarin is low. Data on the important role of the genotype in determining the individual dose and the development of bleeding, which is associated with the metabolism of warfarin, have been obtained. The pharmacogenetic approach allows you to quickly and efficiently choose its dose. The use of generics is highly relevant on the Russian market. Also, a number of regions are of great interest as a basis for conducting clinical trials of drugs.
Aim. To analyze the current use of anticoagulant drugs taking into account personalized treatment approaches (the implementation of pharmacogenetic examinations and the work of anticoagulation clinics).
Methods. Analysis of real clinical practice in the Russian Federation, patient registries, evaluation of adverse events in anticoagulation therapy and pharmacogenetic studies. Analysis of anticoagulant purchase under the Drug Reimbursement Program in several regions of the RF. Evaluation of the effect of anticoagulation clinics throughout the RF.
Results. We analyzed the use of anticoagulants. To reduce the risk of thromboembolic complications and select the appropriate antithrombotic therapy, the entire range of antithrombotic agents is required, including NOACs and vitamin K antagonists (warfarin). Th e appearance of warfarin and NOACs on the Russian market has significantly improved the quality of medical care and treatment outcomes in these patients. Active awareness raising, the addition of anticoagulants to the national clinical guidelines and to clinical practice, and state support as part of the Drug Reimbursement Program have significantly increased the frequency of anticoagulant use. Nevertheless, the frequency of anticoagulant use varies slightly between regions. Warfarin is the most widely used anticoagulant and has high affordability (from 44 to 72.5 % out of all anticoagulants). The frequency of bleeding does not differ significantly between different anticoagulants, with an average of 2.8 %. A first INR value of ≥2.0 aft er 3-5 days is significantly associated with over coagulation during warfarin dose titration. The rapid achievement of an anticoagulation effect is often associated with a specific genotype (CYP2C9*2/*2, *3/*3 and 2/*3 variants and A/A of the VKORC1 gene, or CYP2C9 and VKORC1 polymorphism). Pharmacogenomics-guided warfarin dosing in clinical practice allows the warfarin dose to be selected in a faster and more effective way and for the risk of adverse reactions to be reduced. The creation of a network of anticoagulation clinics has proven to be highly effective. The most well-structured system of anticoagulation clinics is present in the Kursk Region. Rivaroxaban was the biggest selling anticoagulant out of the NOACs on the Russian sales market in 2018, but given the growth in apixaban sales, it is likely that this NOAC will move into first place in the near future.
Conclusion. A personalized approach to anticoagulant use is crucial for the prevention of thromboembolic complications.

Predicting the results of bioequivalence studies is an urgent and important task in developing protocols for clinical studies of bioequivalence. Objective: to develop an algorithm for predicting bioequivalence results based on factors with a sufficient degree of informativeness. Materials and methods: the analysis of the main factors associated with conducting bioequivalence studies on the data of 290 bioequivalence studies; the informativeness of the factors is characterized and the corresponding points (prognostic factors) of each gradation of each factor are determined; a forecast table and forecast calculation algorithm have been developed; The sensitivity and specificity of the developed prognostic algorithm are compared with the control sample (data from 65 bioequivalent studies from open sources). Statistical processing was performed using SSPS Statistics v. 25 and Microsoft Office Excel 2016. Results: The results of the analysis performed to determine the informative factors by various assessment methods are described. Equations are given for performing the corresponding calculations. The key and most informative features are shown, on the basis of which a forecast table is created and a forecast algorithm is developed. The results of the analysis of the sensitivity and specificity of the algorithm for predicting the results of bioequivalence studies are presented. Conclusion: an algorithm and a calculator for predicting the results of bioequivalence based on factors with a sufficient degree of information content have been developed. The algorithm showed high values of sensitivity and specificity, as well as a low percentage of errors.

Relevance. Residency remains an integral part of quality postgraduate education in Russia. Improving the education system of medical workers and creating a system of motivation for their quality work is one of the priority tasks implemented within the framework of the Concept of development of the healthcare system in the Russian Federation until 2020.

Objective. Comparison of the European standard of postgraduate training of medical specialists in the field of “internal diseases” with the existing training system in the Russian Federation.

Results. The residency program of the Russian Federation pursues a similar aim to the European standard — the training of a qualified general practitioner. The program is based on a modular system and includes the study of various disciplines, an extensive practice program and state final certification. An analysis of the content of the work programs of the disciplines indicates that the training is aimed at the formation of both universal (general cultural) competencies, which are essentially similar to CanMEDS, and professional competencies. There is no significant difference between the list of knowledge, skills and practical skills that a general practitioner must possess after graduation from residency in Europe and Russian Federation. However, the development of a similar program in the Russian Federation takes much less time (2 years or 4,320 hours), which raises a logical question about the quality of training.

Conclusion. Despite the diff erence in the programs for postgraduate training of internist (primarily in terms of hours), the learning goal is the formation of similar competencies. It should also be noted a well-structured control system, which makes it possible to objectively evaluate the acquired competencies and adjust the individual learning process.