Objective: to assess clinical and economic implications of adding daratumumab (Dara) to the “lenalidomide + dexamethasone” (Rd) treatment program in early lines of therapy for patients with multiple myeloma (MM) ineligible for high-dose chemotherapy (HDCT) with subsequent autologous hematopoietic stem cell transplantation (autoHPSCT).

Material and methods. Partitioned survival model was developed to compare overall survival in the treatment programs of MM patients in the 1st to 3rd lines of therapy. The following treatment options were included in the analysis: 1st line – Dara+Rd; 2nd line – “carfilzomib + lenalidomide” (K+Rd) or “ixazomib + lenalidomide” (Ixa+Rd) triplets; 3rd line – pomalidomide (Pom+dex) and Rd+(Dara+Rd)+(Pom+dex) versus Rd+(K/Ixa+Rd)+(Pom+dex/Dara). Probabilities of transition between health states (progression-free, progressed disease, and death) were based on published clinical data. Lifetime direct healthcare costs and incremental cost-effectiveness ratios (ICERs) per 1 life year gained were calculated from a Russian health care perspective. The indicator of the difference in costs between current and expected practice was used in budget impact analysis.

Results. Dara+Rd combination increased life expectancy by 1.04 years (+16.05%) and 0.95 years (+14.57%) per patient, and in the target population (n=955) by 995.48 and 903.40 years for (Dara+Rd)+(K+Rd)+(Pom+dex) and (Dara+Rd)+(Ixa+Rd)+(Pom+dex) treatment programs, respectively, compared to Rd use in the 1st line. The ICER per 1 life year gained for Dara+Rd in 1st line therapy was 8.95 mln rubles for (Dara+Rd)+(K+Rd)+(Pom+dex) and 8.41 mln rubles for (Dara+Rd)+(Ixa+Rd)+(Pom+dex). It's lower than the median ICER of 13.64 million per 1 life year gained for antitumor drugs used to treat cancer of lymphatic and hematopoietic tissues (reference ICER). Dara+Rd triplet is used in 2nd line therapy after Rd, the number of life years gained in the target population due to greater efficacy is higher by 291.50 years compared with K+Rd and by 203.93 years compared with Ixa+Rd. The ICER per 1 life year gained for Dara+Rd is also lower than the ICER reference value: 9.25 mln rubles versus 13.64 mln rubles. The budget impact analysis showed that using Dara in early stages of MM therapy does not increase drug provision costs in the target population.

Conclusion. The obtained results allowed to conclude that it is economically feasible to add Dara to the 1st and 2nd lines of therapy in lenalidomide treatment programs for MM patients who are not candidates for HDCT with autoHPSCT.

Objective: to evaluate the pharmacoeconomic efficacy of “atezolizumab + bevacizumab + paclitaxel + carboplatin” drug combination compared to “pembrolizumab + pemetrexed + carboplatin” combination in adult patients with non-small cell lung cancer (NSCLC) in the first line of therapy.

Material and methods. The modeling was applied for cost minimization analyzis of using compared therapy regimens with comparable efficacy, and to estimate the impact on the healthcare budget when increasing the proportion of patients in the target population receiving “atezolizumab + bevacizumab + paclitaxel + carboplatin” combination. Published adjusted indirect comparison data were used in modeling. The calculations were based on the registered prices according to the state register of maximum selling prices.

Results. The use of “atezolizumab + bevacizumab + paclitaxel + carboplatin” combination instead of “pembrolizumab + pemetrexed + carboplatin” combination will decrease the direct medical costs of therapy per 1 patient for 2 years by 28,165.00 rubles (–0.4%). The budget impact analysis showed that an increase in the proportion of patients receiving “atezolizumab + bevacizumab + paclitaxel + carboplatin” combination from 50% (current therapy practice) to 100% (considered therapy practice) will reduce the budget load for the population of 6,240 patients over 2 years by 256.1 million rubles (–0.64%).

Conclusion. The results of pharmacoeconomic analysis demonstrated that the use of “atezolizumab + bevacizumab + paclitaxel + carboplatin” combination in first-line therapy for metastatic NSCLC is economically feasible and reduces the load on the budget compared to “pembrolizu- mab + pemetrexed + carboplatin” scheme.

Objective: to conduct a STEP analysis (social, technological, economic, political) of macro-environmental factors influencing medical and drug care for patients with chronic myeloid leukemia (CML).

Material and methods. The materials used were information from the official website of the Federal State Statistics Service of the Russian Federation (RF), financial reports of the Ministry of Finance of the RF, the Ministry of Industry of the RF, the Federal Customs Service of the RF, the Federal Treasury, the All-Russian Center for the Study of Public Opinion, data from the World Health Organization and the Ministry of Health of the RF, regulatory framework of the RF, data from the State Register of Medicines of the RF and information from domestic and foreign scientific publications. The object of the study was the Department of Hematology and Chemotherapy of the Regional Clinical Hospital No. 1 (Tyumen). Structural, statistical, analytical, situational-logical, mathematical, graphic methods, as well as content analysis, STEP analysis and ranking were used.

Results. Providing medical and drug care to CML patients today is a vital and pressing problem in Russia and around the world. The effectiveness of pharmacotherapy directly depends on certain environmental factors, and each of them influences the functioning of a medical organization (MO) to varying degrees. Analysis of social factors made it possible to trace the dynamics and make a forecast regarding the capabilities of patients and MOs as well as the demand for drug therapy. Economic factors are based on the level of monetary income of the population and the expenditures of the RF budget on healthcare. The role of Russian export and import volumes is shown, first and foremost, the influence of these indicators on domestic prices, demand and on the macro-economic balance in general. Сreditor indebtedness changes the MO financial position and reflects the efficiency of using the monetary resources. Analysis of technological factors allowed assessing the equipment of the MO with medical facilities and drugs. The influence of such factors as the registration of new drugs for the treatment of CML patients and the digitalization program in health care was studied. Based on the analysis of political factors, the state’s interest in the development of domestic medicine and pharmacy was determined.

Conclusion. The STEP analysis of external factors influencing medical and drug care for CML patients allowed identifying the most significant ones for optimizing pharmacotherapy in this category of patients, which is relevant for medical practice and the pharmaceutical industry.

Background. Nonsteroidal anti-inflammatory drugs (NSAIDs) are characterized by ulcerogenic effects and used for effective and safe pharmacotherapy of inflammation and pain. The zinc-containing drug acyzole is a promising anti-inflammatory drug that potentially does not have this drawback. Objective: to conduct chemoreactomic modeling of the pharmacological effects of acyzole and zinc derivatives of well-known NSAIDs (diclofenac, nimesulide, ketorolac).

Material and methods. The analysis of the pharmacological capabilities of NSAIDs was based on a chemoinformatic approach, i.e. comparing the chemical structure of the studied molecules with the structures of millions of other molecules with established molecular pharmacological properties. The analysis procedure was based on the latest machine learning technologies developed in the theory of topological and metric analysis of feature descriptions.

Results. It was shown that acyzole might have an anti-inflammatory effect due to its impact on the activity of cytokines and, partly, on the metabolism of prostaglandins and leuktrienes. The central effects of acyzole are comparable to those of zinc-NSAIDs. The analgesic effect of acyzole may be associated with kinin receptors inhibition, and weak antihistamine and antinociceptin effects. Acizol may also exhibit a gastroprotective effect. It was established that acyzole, to a lesser extent than the reference molecules, negatively affected the metabolism of vitamins and microelements.

Conclusion. Chemoreactomic profiling of acyzole indicates prospects for its use as an anti-inflammatory drug.

Background. The study of drug availability for patients with chronic obstructive pulmonary disease (COPD) represents one of the priority tasks in the organization of effective counteraction to COPD in the Russian Federation.

Objective: to assess drug prices, affordability, and availability for COPD patients.

Material and methods. The analysis of drug availability for COPD patients was carried out according to the methodology of the World Health Organization and Health Action International (WHO/HAI). Bronchodilator and anti-inflammatory therapy of originator brands and lowestpriced generics was evaluated. The consumption volume of the studied drugs was also analyzed using the ATC/DDD (Anatomical Therapeutic Chemical classification / defined daily dose) pharmacoepidemiologic methodology over a three-year period (from 2020 to 2022), taking into account their share of total DDD (drug utilization analysis, DU90%).

Results. According to the results of DU90% analysis, the most purchased drugs for bronchodilator and anti-inflammatory therapy for all the years under study were drugs from the groups of short-acting bronchodilators (salbutamol, fenoterol, ipratropium bromide + fenoterol) and inhaled glucocorticoids (budesonide, beclomethasone). The obtained data were confirmed by the results of the physical availability study. Thus, the highest percentage of physical availability was for short-acting inhaled beta-2-agonists (SABA) (salbutamol). Analysis of drug affordability also revealed a tendential superiority of SABA and short-acting anticholinergics over baseline bronchodilators and antiinflammatory drugs.

Conclusion. Low affordability of the main drugs of baseline therapy contributes to the burden of COPD and necessitates improvement of drug supply mechanisms for individuals, especially those with low material income, which in the long term will significantly reduce the costs of the healthcare system for the treatment of these patients by decreasing the severity and frequency of exacerbations.

Background. The lack of targeted patient recruitment for clinical trials reaches 90%, which leads to failures of a trial as a whole and insufficient access to the necessary treatment or diagnostic method for patients. To find out the reasons for recruitment failures, many factors are considered, the action of which is difficult to assess due to high variability. In general, various factors are named that reduce patient recruitment, while factors that improve it are much less known.

Objective: to investigate changes in the parameters and indicators of patient recruitment for clinical trials depending on the influence of external factors.

Material and methods. A retrospective analysis of four international multicenter clinical trials of phases II–III was performed by 16 patient recruitment parameters and their 6 derivatives (indicators) – both widely used in the literature and newly proposed. A total of 622 patients from 70 clinical centers located in 59 cities of Russia, Ukraine, and Belarus were included in the study. The methods of descriptive statistics and typing were used. To study the influence of factors, internal and external factors were selected, external factors including population size, area and density of residence were analysed, and changes in parameters and indicators depending on the influence of each factor were examined. The area and population density were studied in inseparable connection with each other.

Results. A simple classification of factors was proposed – external and internal to the clinical center where patients were recruited. The factors classified as external were analyzed depending on the change in the proposed parameters of patient recruitment for clinical trials and their relationships – indicators (derivatives). The final rate of patient recruitment and the final number of patients recruited in the population group of 1–2 million people had statistically significant (p<0.05) higher values (0.57±0.20 and 15.08±5.06, respectively) than in group with up to 1 million people – 0.14±0.05 and 3.75±1.24.

Conclusion. For the first time, an extended panel of parameters and indicators that allow evaluating the influence of various factors on patient recruitment for clinical trials was proposed. The value of the proportion of parameters and indicators that had statistical differences among themselves in the group influenced by the population size factor was more than twice as large as the proportion of similar parameters and indicators in the group influenced by area and population density: 47% and 23%, respectively, which may indicate more strong influence of the first factor.

Objective: to assess the degree of doctors’ awareness on the prevention, diagnosis and treatment of patients with osteoporosis.

Material and methods. The study was conducted using the Yandex Forms service through an original anonymous questionnaire comprising 16 questions concerning personal characteristics (specialty, work experience, category, and academic degree), as well as the degree of awareness in the prevention, diagnosis and treatment of osteoporosis. The questions about the treatment of the disease were compiled based on Russian and foreign clinical guidelines.

Results. Knowledge of the causes and symptoms of osteoporosis was relatively high, but further findings from the survey on prevention, diagnosis and treatment revealed a lack of awareness among physicians in this area. Only 13.7% of respondents identified the potential use of the promising FRAX tool in osteoporosis diagnosing, and only 25% correctly selected first-line medications for treating the disease.

Conclusion. The study revealed that doctors lack sufficient knowledge regarding the prevention, diagnosis, and drug therapy for osteoporosis. In our view, this finding underscores the need for a more comprehensive approach to this issue within the context of continuing medical education. The therapy effectiveness and patients’ complience directly depend on the communication between physicians and pharmacists. Therefore, it becomes essential to consider enhancing their collaboration in osteoporosis prevention and management.

Background. The search for an effective and safe pharmacotherapy for tumor diseases includes the evaluation of the action of candidate molecules on various types of tumor cells. Vitamin B12 and its derivatives are promising molecules whose properties can be controlled through chemical modifications.

Objective: conducting in silico chemoreactom screening and in vitro experimental study of aquacobalamin and heptamethyl ester of cyanoaquacobyrinic acid (HECСA).

Material and methods. Chemoreactome screening was carried out on the basis of a problem-oriented theory of chemograph isomorphism analysis, which is an extension of the algebraic approach to machine learning and recognition problems. Trainable algorithms for calculating chemical distances between molecules were used, on the basis of which the values of half-maximal inhibitory concentration (IC50) were calculated. Screening was carried out for 470 cultures of human tumor cells, including SNB19 (astrocytoma), HCT116 (colon cancer), HeLa (cervical carcinoma), BT-474 (breast duct carcinoma), and A549 (lung carcinoma) cell lines. Dicyanocobyric acid heptamethyl ester ((CN)2Cby(OCH3)7) was obtained by boiling a solution of vitamin B12 in methanol with sulfuric acid (1.0 M) for 4 days. HECСA ((CN)(H2O)Cby(OCH3)7) was obtained by vacuum drying an aqueous solution of (CN)2Cby(OCH3)7 (pH 4.0 and 25 °С). The ester structure and purity were confirmed by 1H nuclear magnetic resonance data, elemental analysis, and MALDI-ToF (matrix-assisted laser desorption/ionization time of flight) mass spectroscopy. Experimental studies of tumor cell cultures were carried out using the MTT testwith aquacobalamin and HECСA on cell lines of immortalized (telomerized) fibroblasts (Fb-hTERT), lung carcinoma (A549), and breast duct cancer (BT-474).

Results. Chemoreactome screening of the effects of molecules on tumor cells made it possible to obtain estimates of cell growth IC50 for 470 tumor cell lines. Depending on cell line and vitamin B12 derivative molecule, IC50 values varied in a fairly wide range: from 15 to 2000 nM. In vitro studies on cultures of two human tumor cell lines (BT-474 and A549) and telomerized Fb-hTERT fibroblasts confirmed the cytotoxic effect of aquacobalamin and its hydrophobic derivative HECСA. It was shown that aquacobalamin had weak cytotoxic properties in the concentration range of 3.125–200 µg/l (IC50 > 200 nM), and HECСA significantly reduces the survival of BT-474 and A549 tumor cell lines at high concentrations (100–200 µg/l, IC50 about 100 nM).

Conclusion. Correspondence was shown between the results of in silico chemoreactome screening and in vitro cell culture studies: IC50 values for HECСA were significantly lower than for aquacobalamin, and the conversion factor from chemoreactome estimates to experimental ones was almost the same (2.64 for BT-474, and 2.63 for A549). The results of chemoreactome screening for other tumor cell lines can be used to plan further cell experiments with vitamin B12 derivatives.

The article aims to examine technological, organizational and regulatory aspects of drug quality and safety assurance system, as well as peculiarities in civil circulation of extemporaneous drugs in Latvian pharmaceutical market to improve approaches for statutory regulation of this special and socially significant type of activity of pharmaceutical organizations. This work continues a series of articles about compounding pharmacy practice in different world healthcare systems.

The article describes a clinical case of ectopic pregnancy with localization in the liver. The patient Sh. was admitted to the gynecological department with pain in the lower abdomen and epigastrium. Clinical, laboratory and instrumental examinations were conducted in accordance with clinical recommendations. The examinations showed that human chorionic gonadotropin level was 17,440.85 mIU/ml. Pelvic ultrasound did not determine the fetal egg in the uterine cavity. However, free fluid in the pelvis (about 50 ml) was found. Repeated pelvic ultrasound revealed a paraovarial formation on the right, and free fluid in the pelvis. Laparoscopic surgery was performed, during which a fetal egg was found in the V segment of the liver. Liver resection and cholecystectomy were performed on an emergency basis. This case describes the importance of timely and correct diagnostics and determination of patient management tactics to prevent the development of life-threatening complications.