FARMAKOEKONOMIKA. Modern Pharmacoeconomic and Pharmacoepidemiology

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Vol 14, No 2 (2021)


103–114 131

Objective: comparative assessment of the economic effect of oral vinorelbine when used as indicated, taking into consideration the new registered price.

Material and methods. A clinical-economic study was performed to compare active platinum-containing chemotherapy regimens of the first line for stage IV non-small-cell lung cancer with oral vinorelbine and pemetrexed as well as first-line chemotherapy regimens for metastatic breast cancer presented with oral vinorelbine and ixabepilone alone. A systematic search for information in medical databases was carried out, the cost estimate was made out in accordance with the recommendations of The Center for Healthcare Quality Assessment and Control of the Ministry of Health of the Russian Federation. The direct medical costs were estimated, formed on the basis of the dosage, frequency and dosage regimen of the compared drugs, based on the data of the State Register of maximum selling prices, clinical guidelines for the studied nosologies, and instructions for medical use. The comparison of the economic effect of the studied drugs was carried out in pairs using the cost minimization method with a sensitivity analysis. Further, the calculations of the amounts of reimbursement of medical care provided were made using each of the compared drugs. An economic assessment of the economic effect of oral vinorelbine was carried out taking into consideration the change in the price of the drug and a budget impact analysis with a sensitivity analysis.

Results. It was determined that the use of oral vinorelbine provides financial savings for a medical organization at the amount of 246,042.34 rubles per 6 cycles of chemotherapy for each patient with stage IV non-small-cell lung cancer compared with the use of pemetrexed, and 558,659.32 rubles per year – for the treatment of each patient with metastatic breast cancer compared with ixabepilone. The results of the budget impact analysis showed that the indication of oral vinorelbine saved 3,287,470.56 rubles for the budget fund considering the change in the cost of 1 mg of the drug for a hypothetical population of patients with stage IV non-small-cell lung cancer in 1000 people. This would create the possibility of therapy for additional 15 patients with this diagnosis. The indication of oral vinorelbine in first-line chemotherapy of metastatic breast cancer for a similar target population would save 18,355,043.96 rubles for the budget fund, which makes it possible to treat 15 more patients with this diagnosis.

Conclusion. The use of oral vinorelbine is associated with the saving of financial resources of a medical organization. In addition, the reimbursement for medical care provided from the compulsory medical insurance funds when using regimens with oral vinorelbine is primarily lower than for comparison drugs. Thus, the use of regimens with oral vinorelbine is more beneficial for the payer (the Federal Compulsory Health Insurance Fund) and for the medical organization. The change in the cost of the drug is associated with an increase in the availability of medical care for patients with stage IV non-small-cell lung cancer and patients with metastatic breast cancer.

116–123 142

Objective: to perform cost-effectiveness analysis of the treatment for adult patients with psoriatic arthritis (PsA) with a Russian interleukin- 17А inhibitor netakimab in comparison with other biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) and to evaluate the influence of the inclusion of netakimab in the therapy for PsA on the budget of the Russian healthcare system.

Material and methods. The evaluation of cost-effectiveness was performed from the position of the Russian healthcare system for patients with moderate and severe PsA. The evaluation was performed based on the results of the network meta-analysis of the randomized clinical studies. The criterion of clinical effectiveness included the changes in the condition of the joints by the criteria of the American College of Rheumatology (ACR20, ACR50, and ACR70) and changes in skin symptoms by the index of the prevalence and severity of psoriasis (PASI 75 and PASI 90) with a recalculation into quality-adjusted life-year (QALY). The time horizon of the cost-effectiveness analysis was 2 years. The calculation was based on the registered prices and VAT. If there was an original drug and a biosimilar registered on the pharmaceutical market, the calculation was based on the median of the registered prices. The budget impact analysis of the influence of netakimab inclusion in the therapy for patients with PsA was performed considering the structure of the prescription of bDMARDs and tsDMARDs that was determined in the pharmaco-epidemiological study conducted in the Russian Federation in 2020. The analysis was performed for patients that received medication by the scheme of reimbursement. The time horizon of the study was 3 years old.

Results. In the base-case analysis, the cost-effectiveness ratio for netakimab was 1.210 mln rub/QALY (by 66.2–88.5% lower than in cases when comparison drugs were used). The budget impact analysis showed that the inclusion of netakimab in the therapy for PsA could reduce the costs by 376.60 mln rub (21.1%). Considering budget saving, the number of additional patients that can be treated will increase by 26.7% within 3 years.

Conclusion. Netakimab is characterized by higher cost-effectiveness in comparison with other bDMARDs (adalimumab, golimumab, guselkumab, ixekizumab, infliximab, secukinumab, ustekinumab, certolizumab pegol, etanercept) and tsDMARDs (apremilast, tofacitinib) prescribed in the Russian Federation for patients with PsA. The inclusion of netakimab in the therapy for PsA will reduce the financial burden on the healthcare system.

124–135 97

Objective: early assessming the clinical and economic efficacy of the thrombodynamics test in infertile patients undergoing treatment with assisted reproductive technologies (ART), as well as the impact of this test on the health care budget of the Russian Federation.

Material and methods. The study was carried out on the basis of statistical data on the number of ART cycles, the proportion of patients with hypercoagulation and normocoagulation of blood, data on the clinical effectiveness of ART programs in Russia, including the dependency on the status of blood coagulation, as well as cost data. The analysis was carried out according to three scenarios: 1) thrombodynamics test with subsequent correction of the revealed hypercoagulability status before in vitro fertilization (IVF); 2) thrombodynamics test with the subsequent refusal to perform IVF in patients with hypercoagulability; 3) thrombodynamics test with subsequent correction of the revealed hypercoagulability status before the start of the frozen-thawed embryo transfer. The criteria for clinical effectiveness were the following indicators: the number of children born and the number of potentially saved life years. Clinical and economic efficacy criteria included: total direct medical costs; incremental cost-effectiveness ratio (ICER); changes in the amount of total direct medical costs; resizing effectively and ineffectively spent funds.

Results. The use of the thrombodynamics test will potentially increase the number of children born by 21–33 children and the number of years of life saved, with discounting considered, within the range of 923–1448 years per 1000 ART cycles, depending on the study scenario. The smallest ICER values were observed in Scenario 2, and amounted to 112,120 rubles for 1 child born and 2519 rubles for 1 saved year of life. The highest ICER values were obtained in Scenario 1: 275,576 rubles for 1 child born and 6191 rubles for 1 saved year of life. The use of the thrombodynamics test in women with infertility before ART in Russia will require an increase in direct medical costs from 174 to 425 million rubles (by 1–5% of the initial level of costs) in absolute terms, depending on the chosen scenario with a time horizon of 1 year.

Conclusion. Due to the expected significant improvement in treatment outcomes and the small amount of additional costs, the introduction of the thrombodynamics test into the routine practice of assessing blood clotting in infertile patients before the start of the ART cycle is potentially cost-effective, but further clinical studies are required for a more accurate economic assessment.

136–150 105

Background. The introduction of innovative drugs has significantly increased the treatment effectiveness in patients with relapsed/refractory multiple myeloma (RRMM), but the question of whether these expensive options can be financially secured remains open.

Objective: to assess the cost of triplets of targeted drugs ixazomib, carfilzomib, elotuzumab and daratumumab with lenalidomide and dexamethasone used in the treatment of RRMM, and to determine possible payment options for this therapy at the level of the Russian Federation subjects.

Material and methods. The cost of an annual course of treatment with the studied regimens with centralized purchases and the cost of targeted drugs per hospitalization case were calculated based on the maximum registered prices, recommended doses and treatment regimens. The normative legal acts regulating the payment of drug therapy for multiple myeloma were analyzed and possible financing channels and their limitations were identified. Using the example of the Volgograd and Saratov Regions, tariffs under the compulsory medical insurance system were calculated and their sufficiency in covering the cost of targeted therapy was estimated.

Results. The cost of an annual course of triplet therapy per patient in the case of centralized procurement of drugs ranged from 5.51 million rubles (regimen with ixazomib) up to 8.03 million rubles (regimen with carfilzomib). The cost per hospitalization, depending on the number of doses, ranged from 80,667–242,000 rubles (ixazomib, 1–3 doses) in the Saratov Region up to 239,618–958,472 rubles (daratumumab, 1–4 doses) in the Volgograd Region. Possible reimbursement channels are High-Cost Nosologies (HCN), Obligatory Medical Insurance (OMI) and Regional Drug Coverage (RDC) programs, nevertheless triplet therapy cannot be purchased via the single channel and the combination of them is required. It has been shown that, in most cases, the costs for a case of targeted drug treatment in studied regions are covered by the average tariff for the corresponding diagnosis-related group (DRG), except for cases with a maximum duration in a day hospital setting. An analysis of the RDC lists and the procurement of drugs in the studied regimens at the expense of regional budgets showed that lenalidomide, ixazomib, carfilzomib, elotuzumab and daratumumab are included in the restrictive list in regions 77, 74, 66, 63 and 47, but they are purchased only in regions 15, 24, 6, 4 and 6, respectively.

Conclusion. The use of a triplet with ixazomib is characterized by the lowest costs, which indicates its greater economic attractiveness relative to carfilzomib, daratumumab and elotuzumab in the treatment of patients with RRMM. The tariffs established in the current DRG model retain the possibility of paying for treatment with the high-cost medicines at the expense of the OMI funds in combination with the HCN or RDC programs. There are reasons to believe that the expansion of the list of 14 HCN program will increase the provision of patients with highly effective therapy and also reduce the financial burden on the regions.

151–166 178

Objective: scientific rationale of changing approaches to medical care payment for hospitalization of patients suffering from severe asthma (SA) that require the prescription of biologic disease-modifying drugs (bDMDs) within the constraints of diagnosis-related groups (DRGs) on the level of the Moscow Region.

Material and methods. For the federal model regional adaptation, the authors used the mechanism of subgroups selection in the structure of basic DRG No. 336 st36.003 and No. 139 ds36.004 “Treatment with biologic disease-modifying drugs and selective immunosuppressants” in the round-the-clock (RH) and day-time hospital (DH). Budget impact analysis (BIA) was performed to provide scientific and economic feasibility for the improvement of medical care payment for bDMDs proscribed to patients with SA within DRG at the level of the Moscow Region.

Results. The analysis of cost of drug therapy and medical services per 1 case of hospitalization of patients with SA, that required bDMDs therapy, considering the classification criterion (international nonproprietary name of drugs and drug therapy regimens), showed 10 subgroups in DRG No. 336 st36.003 (level 1) and 9 subgroups in DRG No. 139 ds36.004. Expert estimates on the rate of hospitalizations and drug dosage regimen indicated for patients with SA were used to calculate the relative cost weights (CW). The highest CW was observed in the subgroup that received benralizumab in RH (CW=7.46) and in DH (CW=12.08) conditions. BIA demonstrated 110,103,901.53 rubles (or 31%) budget savings for the health care system of the Moscow Region.

Conclusion. The implementation of the adapted DRG federal model in the conditions of the health care system of Moscow Region is an economically feasible approach to the organization of the inpatient medical care provided to patients with SA needing bDMDs prescription.

167–179 93

Objective: to analyze the availability and affordability of pharmaceuticals for children in need of palliative care.

Materials and methods. The price, affordability and physical availability of pharmaceuticals for children in need of palliative care were analyzed in accordance with the Health Action International guidelines of the World Health Organization. Linear distribution index (LDI) was calculated to produce the best estimates of availability. Research data was sourced from AlphaRM (as of April 26, 2021) and International Medicine Reference Piece Data. The data array was based on the fiscal data provided by pharmacies. The research was carried out on the total population of pharmacies in the Russian Federation (69,050 pharmacies) and in St. Petersburg (1986 pharmacies).

Results. Pharmaceutical price and affordability estimates show that low-priced generics, which cover over 75% of the whole range, have the most optimal median value of the median price ratio (MPR<1) on top of low affordability ratios (AR<1). Ibuprofen, paracetamol, gabapentin, diazepam, morphine, midazolam, and carbamazepine were found to be the least affordable medications, price-wise (MPR>1). Midazolam (AR=2.494), morphine (AR=2.324), and celecoxib (AR=1.373) had low affordability. Notably, prescription-based pharmaceuticals such as diazepam, midazolam, tramadol, morphine, and fentanyl had the lowest physical availability scores (LDI<3%) in the Russian market compared to the relatively high scores of over-the-counter drugs (LDI>60%).

Conclusions. The results call for better organizational action in the pharmaceutical industry to provide due drug regimens to children in need of palliative care.

180–189 89

Objective: to study the prevalence of vitamin D deficiency and analyze the results of therapy in office workers, including an assessment of the quality of life.

Material and methods. An observational non-interventional cross-sectional, cohort, prospective phase IV clinical study included office workers (151 people, age 18–44 years), who were prescribed an aqueous solution of vitamin D. The concentration of 25(OH)D in the blood of patients was measured before and after undergoing treatment. The duration of therapy, depending on the degree of deficiency, was 4 or 8 weeks. The SF-36 scale was used to assess the physiological and psychological status.

Results. In 75.5% of the study participants, a insufficiency or deficiency of vitamin D was detected. Differences in the average content of 25(OH)D in blood serum before and after treatment with vitamin D were statistically significant. The level of vitamin D in blood serum, measured by the content of its metabolite 25(OH)D <30 ng/ml, is regarded as suboptimal, i.e. its insufficiency occurs, and <20 ng/ml – as vitamin D deficiency (p<0.0001). The SF-36 score showed significant statistically significant improvements in overall health, physical functioning, and pain in individuals with vitamin D deficiency after vitamin D supplementation. The use of multiple linear regression demonstrated an association of serum 25(OH)D levels with vitamin D-rich foods taken less than once a week.

Conclusions. Vitamin D deficiency is very common among office workers: 75.5% had D 25(OH)D levels below 30 ng/ml. Vitamin D deficiency is corrected by taking this vitamin. Vitamin D supplementation helps to improve physical and mental health indicators. Serum 25(ОН)D levels are associated with intake of vitamin D-rich foods and duration of vitamin D treatment.

191–211 188

Background. So-called rational drug design is suboptimal when it comes to finding effective and safe drug-based treatment for COVID-19. Another approach seems promising: to reprofile the pharmaceuticals registered in the Anatomical, Therapeutic, and Chemical Classifier (ATC).

Material and methods. Chemoreactome screening, a method that simulates the results of inhibiting viral growth in a cell culture, models the effects of pharmaceuticals on the human virome, and estimates the adverse effects of medicines, was used to reprofile about 2700 pharmaceuticals from the ATC. The information technology behind chemoreactome analysis is based on the topological recognition theory advanced by the Institute of Pharmaceutical Informatics, Federal Research Center for Informatics and Control, Russian Academy of Sciences.

Results. Sixty two pharmaceuticals and 20 micronutrients were found to have a pronounced antiviral effect with minimal side effects. Comparison against data of basic research and clinical trials showed 31 out of 62 pharmaceuticals to have been independently confirmed usable in COVID-19 treatment. These inhibit coronaviral proteins and/or function as adaptogenic molecules that improve the functioning of cells exposed to viral stress. Glucosamine sulfate was found to have the best safety profile and minimum effects on the healthy human virome out of all the tested anticoronaviral micronutrients.

Conclusions. Reprofiling of pharmaceuticals registered in the ATC could significantly speed up the search for more effective and safer drugbased COVID-19 treatments. Several micronutrients show promise for long-term coronavirus prevention, especially in the elderly.

213–224 127

Objective: identification of the relationship between the news coverage of global diseases and the dynamics of the return on shares of the pharmaceutical sector for Russia and the United States.

Material and methods. The empirical base of the study includes more than 700 thousand tweets on Ebola and COVID-19 in Russian and English, news of the RBC news agency. The sentiment of the text was assessed on the basis of five English and four Russian-language dictionaries, the influence of fundamental and textual variables on the profitability of pharmaceutical companies' shares was carried out using the ARMAX-GARCH econometric model.

Results. It has been proven that the dynamics of the stock index of pharmaceutical companies is explained by fundamental (economic) and sentimental factors. News of any epidemics negatively affects the pharmaceutical sector in the US and Russia, that is, there are no industries that benefit from this situation. Pandemic news affects US pharmaceutical companies more than Russian companies. The effect of news influence depends on the level of spread of the disease. News influences not only at the moment of their publication, but also after: there is a "delayed effect". Ebola news affects the American pharmaceutical market for 2 weeks, and the dynamics of the increase in influence can be traced. News on the COVID pandemic amplifies its impact during 1 week for the Russian pharmaceutical market and for 2 weeks for the US pharmaceutical companies. As for news sources, the elastic network has identified more significant variables based on publications from RBC; therefore, Internet publications generate more publicity, shaping a more significant overall sentiment in the markets.

Conclusion. The models developed in the framework of the study and the economic conclusions obtained have not only theoretical, but also practical significance, and can also be used for further research in this area. It is possible to give recommendations on the practical use of dictionaries to assess the sentiment of the text. In our study, the elastic network method chose the Loughran–McDonald dictionary for evaluating economic texts in English and the EcSentiThemeLex dictionary (designed in R and Python programming environments). Avenues for further investigation may include analysis of other sources of information about the pandemic.

225–233 87

Objective: to evaluate the awareness of pharmaceutical specialists on the pharmacotherapy of climacteric syndrome based on survey results.

Material and methods. The authors analyzed 394 surveys of pharmaceutical specialists in Saint-Petersburg. The survey consisted of 13 questions, covered the personal characteristics of the participants (age, education, professional experience) and their knowledge about special medicines and food supplements to control climacteric symptoms, indications, and contraindications.

Results. The results showed that pharmaceutical specialists saw the difference between combined oral contraceptives and menopausal hormone therapy, but they do not know about the protective cardiovascular effects of menopausal hormone therapy. Most specialists consider menopausal hormone therapy more effective than phytoestrogens, but they have no idea how it works. For most of them, there is hardly any difference between various classes of phytoestrogens. In their opinion, medical representatives and scientific conferences are the main providers of medical information.

Conclusion. The analysis of the level of awareness of pharmaceutical specialists about the pharmacotherapy of menopausal syndrome based on the results of the survey revealed insufficient knowledge among pharmacy workers on a number of fundamental issues. Therefore, it is necessary to develop methodological recommendations on menopausal hormone therapy preparations and phytoestrogens-based drugs for pharmaceutical specialists who act as an important intermediate between a doctor and a patient.


235–248 237

Treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) is a current problem worldwide. Currently, special attention is paid to the possibility of using new high-cost chemotherapy regimens in the treatment of MDR/XDR-TB. Numerous studies have shown that, from a clinical point of view, the effectiveness of MDR/XDR-TB therapy increases with the inclusion of bedaquiline, delamanid, linezolid, fluoroquinolones (moxifloxacin, levofloxacin), and pretomanid. At the same time, there is an assumption that the use of new and repurposed anti-tuberculosis drugs (ATDs) may be associated with an increase in overall costs. This paper demonstrates the potential of pharmacoepidemiology and pharmacoeconomics to evaluate the widespread introduction of new anti-tuberculosis drugs (ATDs), taking into account all the typical features of MDR/XDR-TB therapy. The authors analyzed studies of pharmacoeconomic feasibility of using expensive drugs in treatment regimens of pulmonary tuberculosis patients with MDR/XDR pathogen. It was shown that the use of chemotherapy regimens containing new high-cost and highly effective drugs (moxifloxacin, linizolid, and bedaquiline) in rational combinations with other drugs of the basic and reserve series, selected concerning drug resistance of the pathogen, is associated with a significant economic effect. From the applicability of pharmacoeconomic analysis point of view, the introduction of short-term MDR-TB treatment regimens is also a promising direction in phthisiology. The key link to achieve effective MDR/XDR-TB treatment is the use of new drugs. Considering the specificity of pharmacoeconomic analysis in phthisiology and results of existing clinical and economic studies, the authors have formed recommendations aimed at a more complete realization of pharmacoeconomic analysis potential in MDR- and XDR-TB treatment.

249–262 91

A range of 6700 publications from the PubMed database on the association of micronutrient supply and results of antibacterial and antiviral vaccination was reviewed by the method of topologic and metric analysis. This method allows for a selection of features (i.e. key words) by their informativity, the establishment of the most informative that provide the basis for “synthetic” features and algorithms, or the classification of the reviewed text by the relevance to the subject of the study. The results of fundamental studies showed that folates, vitamins A, D, and B12 are the regulators of mitosis of T and B-lymphocytes that exert the functions of the acquired immunity. Such microelements as zinc, iron, selenium, manganese, and omega-3 polyunsaturated fatty acid support the functioning of T and B-lymphocytes (energy metabolism, intracellular signal transmission, and transcription). Clinical studies showed that the support of vaccination with the specified micronutrients not only increases the titre of the respective antibodies to viral and bacterial pathogens but can also prevent unfavorable effects from vaccination. The administration of micronutrients before and after vaccination will contribute to a decrease in the mortality rate and severity of the pathology development (in case of disease). A systematic analysis allowed the authors to determine the perspectives of the proposed measures for an increase in the effectiveness and safety of vaccines, including COVID-19. Additional micronutrient supply contributes to an increase in the effectiveness and safety of vaccination. The application of specialized vitamin and mineral complexes during vaccination is economically feasible and reduces the vaccination risks for patients with polyhypoavitaminoses.

263–269 78

Objective: comparative systematic analysis of clinical trials of staged and simultaneous approaches in the surgical treatment of combined carotid and coronary stenosis based on the literature search.

Material and methods. A systematic literature search was performed in PubMed/MEDLINE, Google Scholar and Scopus using predefined acceptance criteria. To compare data of simultaneous and staged surgery cumulative indicators of heart attack, stroke and mortality, expressed as percentages and absolute numbers, were analyzed; the Mantel–Hensel formula and the χ2 method were used to assess the relative risk of major adverse cardio-cerebral events development and mortality.

Results. The analysis included 7 studies containing one intervention (4 simultaneous and 3 stage methods). The risk of developing myocardial infarction was RR 0.13 (95% CI 0.02–0.67) for simultaneous tactics, and RR 7.79 (95% CI 1.5–40.43) for staged tactics (p˂0.005). The risk of stroke developing was RR 1.29 (95% CI 0.56–2.99) for a simultaneous approach, and RR 0.78 (95% CI 0.33–1.8) for stage approach (p˃0.05). The risk of mortality was RR 0.77 (95% CI 0.31–1.88) for simultaneous procedures, and RR 1.3 (95% CI 0.53–3.18) for staged procedures (p˃0.05).

Conclusion. Staged tactics for combined carotid and coronary stenosis may be accompanied by a significantly higher risk of myocardial infarction. There was no statistically significant difference between the groups in terms of the risk of stroke and mortality, but there was a trend towards a higher risk of stroke in the simultaneous group and a higher risk of death from all causes in the staged group.

270–276 115

The article provides an overview of the advantages and issues associated with the use of artificial intelligence (AI) and machine learning (ML) in medicine. Based on the analysis of scientific publications, the leading healthcare areas using AI and ML have been identified. The applied problems that modern technologies allow to solve are described, as well as the goals that can be achieved using such technologies. The legal protection issues of technologies using AI are highlighted. A comparison is given of the key aspects of copyright and patent law, and the advantages of patent law and comprehensive patent protection of technologies for process automation in healthcare are presented. The possibilities of complex patent protection and its strategy in the leading areas of AI use in healthcare are considered on specific examples.

ISSN 2070-4909 (Print)
ISSN 2070-4933 (Online)