FARMAKOEKONOMIKA. Modern Pharmacoeconomic and Pharmacoepidemiology

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Vol 13, No 2 (2020)


101-111 245

Aim. To assess the economic efficacy of a fixed combination tiotropium bromide+olodaterol (T+O) in comparison with other medications, included in the Vital and Essential Drugs List (VEDL), for the maintenance triple therapy of chronic obstructive pulmonary disease (COPD).

Materials and Methods. A Markov model was used for the estimation of direct medical costs associated with different medications. Costminimization and budget impact analyses were performed.

Results. The drug costs for T+O were the lowest among all compared treatment strategies. The cost savings in favor of T+O were 24.82% [15.86–29.95%]. The application of T+O strategy in 4,101 target patients led to a decrease in the total direct medical costs under the state programs of guarantees of free medical care by 13.13% in 3 years, which will make T+O therapy available to 643 more patients in the first year and 1,624 patients in three years.

Conclusion. A fixed combination T+O is a preferred efficient option for maintenance triple treatment for patients with COPD in comparison with other drugs from VEDL, because it is associated with lower total costs and equal efficacy.

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The article presents a description of amendments of the Russian Federation Government Decree No. 871 from August 28, 2014 (with amendments from November 20, 2018). The authors analyzed the historical development of approaches for complex drug assessment in Russia, also criteria for its evaluation were under investigation. The changes affecting both the order and the procedure of forming the lists of medical drugs for medical use are reviewed. The particularities of the current procedure for the formation of lists of drugs for medical use are described in detail. In reliance on the analysis, further direction for improvement/development of the system of formation the lists of medical drugs for medical use are educed (List of Vital and Essential Medicines, List of Medical Drugs for Certain Categories of Citizens, List of High-Cost Medical Drugs).

124-131 154

Aim. To evaluate clinical-economical effectiveness of direct oral anticoagulants (DOAC) dabigatran, rivaroxaban, and apixaban in comparison with warfarin in atrial fibrillation (AF) therapy.

Materials and Methods. Mathematical modeling (tree derivation of solutions) on a temporary 5-year horizon from the medical healthcare system perspective. Methods of clinical-economic analysis: analysis “cost-effectiveness”, “budget impact”, and “the analysis of unseized opportunities”.

Results. Total direct costs (DC) were lower by 10.3% when dabigatran was used, by 5.2%, when rivaroxaban was used, and by 10.9%, when apixaban was used in comparison with warfarin. The most significant difference was observed due to different cost of therapy for bleeding complications (in the structure of the costs, it occupied 30-38%). In the group of dabigatran, DC on bleeding complications were lower than in the group of warfarin by 22.0%, in the group of rivaroxaban – by 10.9%, in the group of apixaban – by 36.8%. Besides, in the group of dabigatran, the costs associated with the treatment for ischemic stroke were lower by 28.1% The strategy of the application of DOAC in comparison with warfarin provided more adjusted life years (ALY), complications adjusted life years (CALY), and its lower cost. The application of DOAC saves significant funds. At the same time, the saved funds will provide the purchase of additional modern drugs for patients. The cost-cutting reaches 12% for 5 years and up to 33 patients out of 1000 can receive additional treatment.

Conclusion. Due to the prevention of thromboembolic complications in patients that received direct oral anticoagulants, the direct costs can be reduced by 28.1% and due to the prevention of bleeding complications – by 36.8% in comparison with the application of warfarin. Direct oral anticoagulants provide more adjusted life years and complications adjusted life years at a lower cost. 

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Introduction. The COVID-19 pandemic revealed the vulnerability of the general population to this infectious disease, which is determined by the lack of immunity to the new SARS-CoV-2 coronavirus and is characterized by cytokine storm in severe cases. One of the most important reasons for this vulnerability is a high occurrence rate of micronutrient deficiencies, and above all, vitamin D deficiency.

Aim. To systematize the available data on the role of vitamin D in the prevention of COVID-19 infection.

Materials and methods. Systematic computer analysis of the entire array of available scientific publications on coronaviruses (21,300 publications in PUBMED and preprint repositories, including 7,500 publications on COVID-19 and SARS-CoV-2) was performed. The methods of topological and metric data analysis were used. About 50 most informative sections were identified that were mainly associated with COVID-19 / SARS-CoV-2. The analysis of the obtained “map” of molecular pathophysiology of COVID-19 was performed.

Results. Vitamin D activates the expression of many genes involved in supporting the immunity against coronaviruses and other singlestranded RNA viruses (interferon-dependent protection). The results of the systematic analysis of the publications on coronavirus showed that vitamin D is important for attenuating the effects of the cytokine storm and compensating for chronic comorbid pathologies.

Conclusion. The compensation for vitamin D deficiency is an essential component of COVID-19 prevention. This tactics of prevention is less costly than managing patients with severe forms of COVID-19 and can help save public healthcare resources.  

146-163 276

Introduction. The English-language databases PubMed/MEDLINE and Embase are valuable information resources for finding original publications in basic and clinical medicine. Currently, there are no artificial intelligence systems to evaluate the quality of these publications.

Aim. Development and testing of a system for sentiment analysis (i.e. analysis of emotional modality) of biomedical publications.

Materials and methods. The technique of analysis of the “Big data” of biomedical publications was formulated on the basis of the topological theory of sentiment analysis. Algorithms have been developed that allow for the classification of texts from 16 sentiment classes with 90% accuracy (manipulative speech, research without positive results, propaganda, falsification of results, negative personal attitude, aggressive text, negative emotional background, etc.). Based on the algorithms, a scale for assessing the sentiment quality of research (β-score) is proposed.

Results. Abstracts of 19.9 million publications registered in PubMed/MEDLINE over the past 50 years (1970–2019) were analyzed. It was shown that publications with low sentiment quality (the value of the β-score of the text is less than zero, which corresponds to the prevalence of manipulative and negative sentiments in the text) comprise only 18.5% (3.68 out of 19.9 million). The greatest values of the β-score were characterized by publications on sports medicine, systems biology, nutrition, on the use of applied mathematics and data mining in medicine. The rubrication of the entire array of publications by 27,840 headings (MESH-system of PubMed/MEDLINE) indicated an increase in the β-score by years (i.e., the positive dynamics of sentiment quality of the texts of publications) for 27,090 of the studied headings. The most intense positive dynamics was found for research in genetics, physiology, pharmacology, and gerontology. 249 headings with sharply negative dynamics of sentiment quality and with a pronounced increase in the manipulative sentiments characteristic of the tabloid press were highlighted. Separate assessments of international experts are presented that confirm the patterns identified.

Conclusion. The proposed artificial intelligence system allows a researcher to make an effective assessment of the sentiment quality of biomedical research papers, filtering out potentially inappropriate publications disguised as “evidence-based”.  

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Aim. To review scientific publications on clinical effectiveness and potential application of phytoestrogens (PE) in the treatment of climacteric syndrome.

Materials and methods. The PRISMA approach was used. The systematic search was performed in three electronic scientific databases: Cochrane library, PubMed/MEDLINE, and The publications were also manually searched for in the reference lists of the relevant articles.

Results. The filters were used to select 79 publications; 26 of them were included in the final review. The main method of treatment for the manifestations of the climacteric syndrome is menopausal hormonal therapy (MHT). One of the alternative methods for the control of its symptoms is the application of phytoestrogens (PE), primarily, isoflavones, lignans, and coumestans. Active metabolites of PE are expressed under the influence of gut microflora that is different in various groups of women, which can determine the differences in the effectiveness. Taking into account multidirectional character of the studies as well as numerous publications of low quality, it is still impossible to come to the final conclusion on the effectiveness of PE-containing food supplements (FS) when it comes to a decrease in the occurrence rate and expression of such symptoms as hot flushes, night sweats, and cognitive deterioration. The conclusions on the prevention of cardio-vascular diseases are not definite either.

Conclusions. The review showed that scientists could not come to the conclusion on the effectiveness and safety of PE-containing FS. Probably, the most prospective means of the control of climacteric syndrome are FS that contain isoflavones of red clover and soy in the maximum effective concentration. Considering free access to such FS on the market, they must meet high safety requirements.

Review article

170-182 215

Aim. To review foreign approaches to the evaluation and financing of in vivo gene therapy drugs.

Materials and Methods. The first stage of the review included the systematic search for publications of clinical-economic studies (CES) on in vivo gene therapy drugs registered on the international pharmaceutical market. The analysis of the methodology used in the found CESs was performed based on the given criteria. The second and third stages of the review included the search for the information on the approaches and results of the evaluation of in vivo gene therapy drugs by foreign agencies on the assessment of healthcare technologies (AHT) and the implemented approaches to the financing of expensive medical technologies.

Results. Totally, four in vivo gene therapy drugs registered on the foreign markets were found: talimogene laherparepvec (Imlygic), voretigene neparvovec (Luxturna), onasemnogene abeparvovec (Zolgensma), and alipogene tiparvove (Glybera). The analysis of the methodology of CES on in vivo gene therapy drugs did not reveal general methodological peculiarities. The analysis of the approaches to the reimbursement for the cost of these four drugs in the European countries showed that there were no special procedures intended for gene drugs. However, in the majority of countries, there are some mechanisms of reimbursement for orphan drugs and the majority of the above-mentioned in vivo gene therapy drugs are orphan. It was revealed that the most perspective methods of payment for in vivo gene therapy drugs were installment payments, risk-sharing agreements, and their combinations. Still, none of these payment methods are implemented in Russia because of the lack of regulatory and legal framework.

Conclusion. The design and methodological peculiarities of CES on in vivo gene therapy drugs are similar to orphan drugs (in some countries, there is a special flexible procedure). In the Russian Federation, there is no special procedure of ATH for orphan drugs, which can provide difficulties in the reimbursement for these drugs. Besides, in the Russian Federation, the issue of the implementation of innovative models for drugs provision (risk-sharing, installment payments is acute). The changes in this area would also lead to the optimization of the influence of expensive healthcare technologies on the budget of the system of healthcare.

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Chondroitin sulfate (CS) and glucosamine sulfate (GS) are used in the treatment of osteoarthritis and exhibit a pronounced anti-inflammatory effect. CS/GS inhibit the NF-kB signaling cascade, which realizes the biological effects of tumor necrosis factor (TNFa). Excessive activity of NF-kB also stimulates the development of atherosclerosis. The results of experimental and clinical studies show that inhibition of NF-kB by CS/GS will inhibit the formation and growth of atherosclerotic plaques also reducing levels of other markers of inflammation.


193-204 149

Aim. To analyze the methods of the state regulation of prices for the manufacturers of pharmaceutical drugs in the Eurasian Economic Community counties (EAEC).

Materials and Methods. The comparison of the aspects of the price regulation was presented as short characteristics of the regulating impact of the key normative legal acts (NLA) in the sphere of price formation on pharmaceutical drugs in the EAEC. The study included the following stages: the analysis of NLA in the Russian Federation, Republic of Belarus, Republic of Kazakhstan, Republic of Moldova, Republic of Armenia, and the Kyrgyz Republic, the comparison of the list of reference countries, and decreasing coefficients.

Results. The authors revealed the differences in the procedure of the registration, re-registration, referencing of prices, and decreasing coefficients for the generics. The authors highlighted the drawbacks of the existing procedure of the registration of prices in Russia in terms of the formation of the list of the referent countries, the re-registration of drugs with an increase in price, and limited economic efficiency.

Conclusion. The performed analysis showed that the differences in the methods of the state regulation of prices on pharmaceutical drugs in the EAEC countries do not allow for the formation of a unified approach. However, the creation of supranational method of price formation is an essential condition for the functioning of the united market of pharmaceutical drugs.


205-219 351
Gallstone disease is revealed in 10–20% of the population with a clear tendency to affect the younger population. In a clinically manifested course, cholecystectomy remains the treatment of choice. Symptoms and signs persist or even become more severe after gallbladder surgery in 10-15% of cases (“postcholecystectomy syndrome”). Postcholecystectomy syndrome includes heterogeneous disorders of liver, pancreas, duodenum, sphincter of Oddi, etc. that can be associated with errors or negative consequences of surgical intervention. Often, symptoms may persist because of previously unrecognized chronic diseases of neighboring organs. The spectrum of effective conservative measures is rather limited. The Advisory Board was held on May 4, 2019, in Almaty (Kazakhstan) to re-estimate the definitions and categories related to the issue of the postcholecystectomy syndrome and to develop the diagnostic and treatment algorithm for patients with the postcholecystectomy dysfunction of the sphincter of Oddi. The statements discussed by the interdisciplinary team of gastroenterologists and surgeons were addressed to general practitioners, therapists, gastroenterologists, and surgeons. The Advisory Board emphasized that organic and functional biliary diseases manifest mainly by biliary pain, main characteristics of which were defined in the Rome IV consensus based on the statistical analysis of a large pool of clinical data. For a more accurate bile duct system assessment and the exclusion of cholelithiasis, the examination algorithm was proposed, which included abdominal ultrasound investigation, endoscopic ultrasound investigation of the pancreatobiliary area, and magnetic resonance cholangiopancreatography. Diagnostic algorithm for differentiation of functional biliary disorders from organic gastrointestinal pathology was developed. Sphincter of Oddi dysfunction may be considered as a postcholecystectomy syndrome manifestation in 1.5-3% of cases. Apart from rational nutrition, conservative management of functional gastrointestinal diseases implies  pharmacological therapy. The efficacy of non-steroidal anti-inflammatory drugs, prokinetics, nitrates, antispasmodics, calcium channel antagonists, botulinum toxin, and hymecromone was demonstrated in previous studies. Papillosphincterotomy is not effective in relieving biliary pain in cases of the sphincter of Oddi dysfunction. The proposed algorithm for the management of patients with the postcholecystectomy syndrome was presented.

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