Objective: to review legislative and regulatory legal acts and other documents and consider the changing requirements for the development of medical care standards and the current standard form, to determine the key principles and methodology for the development of medical care standards based on clinical guidelines.

Material and methods. The article reviews the provisions of the Federal Law of November 21, 2011, No. 323-FZ “On fundamentals of health care in the Russian Federation”, which establishes the requirements for the development of medical care standards. A review of the procedure for the development of standards (Orders of the Ministry of Health of the Russian Federation (MH RF) of February 8, 2018, No. 53n and of February 22, 2022, No. 103n) was conducted. The form of the medical care standard was considered based on the example of the medical care standards approved in 2021–2022. A review of methodological materials regulating the development of medical care standards based on clinical guidelines was performed.

Results. The procedure for developing medical care standards was first regulated in 2018. The participants of the process (MH RF departments, MH RF chief external specialists, Center for Expertise and Quality Control of Medical Care), their functions, and the stages and terms of development are regulated. The methodology for the development of medical care standards based on clinical guidelines involves the formation of standardized modules of medical care and a mathematical model.

Conclusion. Currently, the process of developing medical care standards based on clinical guidelines is regulated and the methodology is defined. However, there are still issues that require additional regulation, such as the standard form, the methodology of medical and economic evaluation.

Objective: to evaluate the clinical and economic feasibility of expanding the preferential drug provision (PDP) program for adult patients at very high cardiovascular (CV) risk, including those who have not reached lipid targets on statin therapy, by increasing the frequency of use of ezetimibe, alirocumab, evolocumab and inclisiran used in combination with statins, compared with current PDP practice (use of atorvastatin, simvastatin and minimal use of other drugs).
Material and methods. A Markov model was constructed to characterize the development of atherosclerotic heart disease in patients with very high CV risk and to suggest a consistent change in hypolipidemic therapy if it is ineffective. The model considered patients' compliance to drug therapy over time and the factor of non-prescription of any treatment. The modeling horizon was 30 years, and the model cycle was 1 year. The outcomes used were quality-adjusted life years (QALY), life years gained (LYG), and probabilities of various individual and combined CV events. The baseline modeling scenario was to increase the frequency of рroprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors’ prescriptions. In addition, alternative scenarios were modeled that included prescription of highly effective lipid-lowering therapy for all patients who had not reached target low-density lipoprotein cholesterol (LDL-C) on statin therapy, and the scenario with 100% compliance to statin therapy.
Results. In comparison with current practice of treatment of patients with very high CV risk, clinical and economic modeling showed a decrease in the incidence of combined outcomes (combined CV events – by 8%, extended combined CV events – by 9%) and individual CV events (heart attack – by 4%, stroke – by 3%, unstable angina – by 2%, revascularization – by 3%) in the baseline scenario. In scenarios of prescribing PCSK9 inhibitors and inclisiran to all patients who have not reached target values of LDL-C on statin therapy, the frequency of individual events ranged from 4% to 8%. In the scenario, which also implies 100% drug compliance, the reduction was from 8% to 17% compared with current patient management practices, characterized by lower frequency of hypolipidemic drugs, including PCSK9 inhibitors and inclisiran. The incremental cost-effectiveness ratio (ICER) for QALY in the baseline scenario was 3,598,156 rubles, the ICER for LYG was 1,949,393 rubles. When comparing the ICER with willingness-to-pay (WTP) threshold in the Russian Federation (calculated as three times the gross domestic product per capita and in 2022 amounting to 2.8 million rubles per effect unit) the ICER for LYG did not exceed the WTP in all scenarios, while the ICER for QALY exceeded the WTP by 29–44%, depending on the realized scenario.
Conclusion. Expanding the PDP program for high CV risk patients will have a positive impact on their quality of life and life expectancy, as well as significantly reduce the likelihood of acute CV events. Comparison of ICER with estimated WTP suggests that expansion of the PBP program is a cost-effective organizational technology according to LYG criterion, but not according to the QALY criterion.

Objective: evaluation of the clinical and economic efficiency of using Levilimab in the treatment of moderate and severe COVID-19 based on real world data (RWD).
Material and methods. A single-center observational retrospective case-control study was performed. According to the matching algorithm, 834 pairs of patients with moderate and 347 pairs with severe infection were selected, similar in gender, age, vaccination status, severity of the disease and the level of C-reactive protein.
Results. The clinical efficiency of Levilimab with respect to in-hospital mortality was demonstrated both for the moderate course (6% in the Levilimab group and 10% in the standard therapy group; odds ratio (OR) 1.71; 95% confidence interval (CI) 1.19–2.47; p<0.01) and for the severe course of COVID-19 (63% and 82%, respectively; OR 2.70; 95% CI 1.90–3.82; p<0.01). The costs per 1 treated patient were also higher in the Levilimab therapy groups: the difference in costs compared to the standard therapy group for patients with moderate disease was 54 665.30 rubles, with severe disease – 91 285.85 rubles. The estimated cost of the additional effectiveness of Levilimab for the moderate course of the disease was 13,666.32 rubles, for the severe course – 4,804.51 rubles.
Conclusion. The use of Levilimab for the treatment of moderate and severe COVID-19 is feasible both from a clinical and economic points of view. Conducting RWD trials is an important tool to understand the effectiveness of medical technologies in real clinical practice.

Objective: to perform a clinical and economic analysis of using drugs containing follitropin alfa as an active substance and to assess the impact of the studied drugs on the budget of the state healthcare system of the Russian Federation considering cost data for 2022 in the population of women with infertility and poor ovarian response who are undergoing treatment with the use of assisted reproductive technologies (ART).
Material and methods. Clinical and economic evaluation of follitropin alfa use in patients with infertility and poor ovarian response was performed by a cost minimization method, using data from the Uniform Information System for Procurement for the period from July to December 2022 inclusive. The budget impact analysis model compared the costs required for ovarian stimulation of patients with poor ovarian response receiving only a fixed dose combination (FDC) of follitropin alfa + lutropin alfa with the expected practice of switching 25% of these patients to follitropin alfa with a modeling time horizon of 1 year.
Results. A cost analysis of an ovarian stimulation course using biosimilar follitropin alfa showed cost savings of 17% compared with the cost of therapy using the original follitropin alfa. Also, cost minimization analysis per cycle of ovarian stimulation demonstrated that the use of the biosimilar follitropin alfa was characterized by cost savings of 24,420 rubles (32.37%) compared to FCD of follitropin alfa + lutropin alfa. Compared to the 2021 data, in the current study based on 2022 data and including only biosimilar follitropin alfa, there was a 103% increase in savings. Budget impact analysis determined that switching 25% of the population from FCD of follitropin alfa + lutropin alfa to follitropin alfa would reduce direct medical costs by 17.3 million rubles (8.1%) per year. Savings in direct medical costs in the current study compared to 2021 increased by 117%.
Conclusion. The clinical and economic analysis, as well as the budget impact analysis of using biosimilar follitropin alfa for ovarian stimulation in a population of women with infertility and poor ovarian response, confirm the economic expediency revealed in 2021. Moreover, according to 2022 data, the use of biosimilar follitropin alfa results in additional budgetary savings.

Objective: description of the current problems concerning the development and conducting of a protocol of clinical approbation (CA) of methods of prevention, diagnosis, treatment and rehabilitation to optimize the implementation of innovative medical technologies in practical health care through CA.
Material and methods. The review of the legislative framework governing CA and analysis of the proceedings of CA issues strategic session were carried out, management decisions to improve the effectiveness of CA were proposed. Analysis of legal acts stipulating the notion and status of CA was performed. The study included orders of the Ministry of Health of the Russian Federation, which established regulations on the organization of CA, the CA protocol templates, etc. Methodological materials, review articles on the organization of health care in the Russian Federation selected from various open sources were studied. The basis for making management decisions on improving the quality of CA procedure was formed by the participants of the CA issues strategic session which had been initiated by the Center for Healthcare Quality Assessment and Control.
Results. Based on the results of the strategic session and the analysis of legal acts, current issues related to CA regulation, such as lack of СА coordination and research publications, poor methodological quality of clinical and economic evaluations within CA, promotion of innovation through CA were identified. The developed managerial decisions on improvement of CA and promotion of innovations in practical health care were presented.
Conclusion. Current legal acts regulating CA activities should be updated with a view to establishing a transparent system of clinical and economic evaluations of new and innovative methods for making an informed decision to include them in clinical guidelines and routine clinical practice. It is proposed to legally assign the functions of CA coordinator to the federal medical development organizations. Regarding the promotion of innovative technologies in practical health care, it is advisable to create a system for the introduction of innovations, including taking into account conducting CA.

Objective: the development and verification of a scale for identifying patients at high risk of osteoarthritis (OA).

Material and methods. The results of the analysis of a sample of patients aged 35–90 years from the database of the Institute of Trace Elements (n=3440), which included information on clinical and anamnestic, diagnostic parameters and pharmacotherapy of patients, including patients with OA (n=107), are presented. To analyze information about patients, modern methods of data analysis proposed within the topological theory of pattern recognition were used.

Results. Based on the analysis of the sample, a 100-point scale of 27 points was developed which allows to identify patients at high risk of OA (sensitivity 88%, specificity 100%). For patients with high scores on the scale, a kind of “preemptive” prescription of symptomatic slowacting drugs for osteoarthritis (SySADOA) based on highly purified substances of chondroitin sulfate (CS) and glucosamine sulfate (GS) is promising. The evidence for CS/GS is extensive and has been reviewed previously.

Conclusion. Early adoption of preventive measures (including the usage of SySADOA – CS/GS) in patients with a high score on the developed scale may reduce the risk of OA.

In order to improve regulation of socially significant type of activity in the field of compounding pharmacy production, the review summarizes the technological, organizational and regulatory requirements for ensuring quality and safety of compounding drugs, as well as historical and technical analysis of the compounding pharmacy regulation in North American pharmaceutical market. The main imperatives are identified and the best practices recommended for implementation into the current state of the pharmaceutical market in the Russian Federation. 

The results of published studies of modern biomarkers used in the diagnosis of acute kidney injury (AKI) were summarized. The search was carried out in the PubMed/MEDLINE, Scopus, eLibrary databases. AKI occurs in 10–15% of all inpatients and 50% of intensive care patients, and affects economic aspects of treatment and rehabilitation. The literature review allowed to draw conclusions about the significant advantage of new AKI biomarkers (cystatin C, neutrophil gelatinase-associated lipocalin, β2-microglobulin, kidney injury molecule-1, fatty acid binding protein) over the conventional glomerular filtration rate, serum creatinine and urinary volume. Serum creatinine increases only in cases when 50–60% of nephrons are damaged, urinary volume has limitations such as the overdiagnosis of AKI in dehydrated patients, the inability to assess based on a single measurement, and the need for regular and frequent follow-up. Modern biomarkers make it possible to verify renal dysfunction in advance, at the subclinical level. This allows to make a correction in the therapy of the underlying disease and initiate nephroprotection to prevent the development of AKI and the further development of multiple organ failure, which may be more effective than the treatment of already developed AKI. 

Background. The rapidly developing resistance of viruses to synthetic antiviral drugs indicates the need to use substances with multitarget action (to avoid polypharmacy and to improve the safety of treatment).

Objective: systematic analysis of the scientific literature on the pharmacology of bioflavonoids with an emphasis on their antiviral action.

Material and methods. More than 150,000 references of primary sources were found in the PubMed/MEDLINE database of biomedical publications, including 3282 references on the antiviral effects of bioflavonoids. A systematic computerized analysis of this array of publications was carried out in order to identify the main directions in the pharmacology of bioflavonoids with an emphasis on their antiviral, antibacterial and immunomodulatory effects. The literature analysis was carried out using modern methods of topological and metric analysis of big data.

Results. The molecular mechanisms of action of baicalin, hesperidin, rutin, quercetin, leukodelphinidin bioflavonoids and epigallocatechin-3-gallate, curcumin polyphenols, their anti-inflammatory, antioxidant, antiviral, bactericidal, angioprotective, regenerative effects, and their prospects in therapy, prevention and rehabilitation of patients with COVID-19 and other respiratory viral infections were described in detail.

Conclusion. Bioflavonoids and synergistic polyphenols exhibit not only multitarget antiviral effects by inhibiting the main protease, spike proteins, and other target proteins, but also pronounced anti-inflammatory, hepatoprotective, and immunomodulatory effects.

High-throughput next-generation sequencing (NGS) technologies such as whole exome sequencing (WES) and bulk RNA sequencing (RNA-seq) allow identification of the new biomarkers of response and resistance to antitumor therapy. Retrospective studies have shown that the state of the tumor microenvironment (TME), identified via RNA-seq, is an independent prognostic and predictive biomarker. WES and RNA-seq technologies, along with classical immunohistochemistry, provide a comprehensive analysis of the tumor and TME. Affordability of high-throughput sequencing will enable personalization of antitumor pharmacotherapy.

Acute respiratory failure (ARF) is the leading cause of death in hospitalized patients with severe forms of COVID-19. At the beginning of COVID-19 pandemic the starting respiratory protocol suggested early use of intubation and artificial lung ventilation (ALV) in patients with severe pneumonia complicated by ARF. However, after the analysis of the published studies it was noted that the pathophysiology of the development of ARF in COVID-19 had features that determine the atypical clinical pattern – “silent hypoxemia”. This leads to the late onset of respiratory support (RS) and, as a result, to the lower effectiveness of non-invasive RS methods. This article discusses the creation of an algorithm for the early use of various non-invasive RS methods in patients with COVID-19 complicated by ARF, that will decrease the frequency of hospitalization to the Intensive care units, tracheal intubation and ALV, reduce the duration of treatment and improve prognosis.