Goal: to conduct pharmacoeconomic analysis of using the darbepoetin alfa (Aranesp) and other erythropoiesis-stimulating agents for anemia correction in patients on hemodialysis or peritoneal dialysis. Methodology. The study included both original medications: darbepoetin alfa (Aranesp), epoetin alfa (Eprex), methoxy polyethylene glycol-epoetin beta (Mircera), and bioanalog - epoetin alfa (Eralfon). Due to the fact that data are available regarding the discrepancy between the actual dosage of darbepoetin and instructions for drug use (meta Bonafont et al.), to assess the actual practice in a national health system was conduct a retrospective observational study in 11 hospitals of different regions of Russia. Budget Impact Analysis (BIA) was used as the most informative method to identify sources to optimize budget spending allocated for drug coverage this category of patients - only direct medical cost took into account such as cost of the drugs, intravenous administration, the transfusion and the cost of unplanned hospitalization for cardiovascular reasons or due to infection. The same calculation was made changes total cost (savings budget) at a magnification of hospital purchases Aranesp share 15% (± 5% of each of the compared drugs) depending on the target value of the level of hemoglobin. One-way sensitivity analysis of the model to the price of Aranesp ± 10% and reduce the dose of Aranesp by 20% and 47% (based on expert data), as well as to changes in the cost of hospitalization was spend. Results. Data on the efficacy and safety of different types of anemia correction in patients on hemodialysis or peritoneal dialysis have been analyzed. In the literature review was concluded on a similar efficacy and safety of drugs included in the study. Cost analysis showed darbepoetin economic advantage for all the analyzed indicators (total costs per patient attained control, the total annual costs). Sensitivity analysis showed that the results are most sensitive to a change in dose and price of darbepoetin. Despite the fact that these actual practices indicate a possible reduction in the dose of Aranesp by 47%, the economic benefit of the drug Aranesp maintained even at reduction by 30%. Conclusions. Using Aranesp in dosages used in actual practice for correction of anemia in patients undergoing hemodialysis or peritoneal dialysis is more cost-effective way of treatment compared with other alternative erythropoiesis-stimulating drugs.

Chronic pain syndrome (CPS) is a complex, hard to treat polyetiological condition. While there is a wide array of possible causes for CPS, it is most important in oncological context, since within oncological setting it may be induced both by the tumor itself and by the treatment modalities used against it. Analgesic therapy is, according to WHO, the primary method of managing CPS, and is effective in approximately 90% of cases. However, patients requiring strong opioids for pain management (III step of WHO’s “analgesic ladder”) face a number of complications associated with adverse events (AE), such as inhibition of respiratory control center, nausea, vomiting, and constipation. While constipation and vomiting are themselves amenable to therapeutic management, they can both significantly reduce quality of life and even require alteration of analgesic medication regime, thus potentially compromising the management of chronic pain. This has necessitated the creation of painkiller medication that would have a more favorable gastrointestinal AE profile while maintaining analgesic efficacy, such as fentanyl transdermal delivery systems (TDS) and oral formulations combining oxycodone and naloxone. The pharmacoeconomic comparison of these two medications in order to determine which of them is more economically rational within context of Russian healthcare is thus justified, and is the subject of this research effort. Aim. To perform evaluation of pharmacoeconomic (PHe) properties of combined naloxone/oxycodone formulation (Targin®) compared to fentanyl TDS (Fendivia®) in Russian oncological patients with CPS. Methodology. This PHe is conducted perspective of public health organizations of the RF at federal and national levels. The modelling horizon was 25 weeks. Comparator drugs were Targin® and Fendivia®. Randomized controlled clinical trials investigating safety and efficacy of these drugs were used as data source on safety and efficacy. A Markov model was constructed in order to estimate healthcare costs and patients outcomes. Each simulated patient group contained 100 patients. Retention of patients with adequate pain management in main treatment regime without dose increase was used as efficacy criterion, since this surrogate endpoint is most clinically relevant, reflecting ability of a given modelled treatment regimen to control chronic pain. These modelling results were used to perform the following types of pharmacoeconomic analysis: carrying out cost-effectiveness analysis (CEA), budget impact analysis (BIA), and evaluation of pharmacoeconomic expediency based on willingness-to-pay ratio (WTP). Result. Naloxone/oxycodone formulation dominates in CEA analysis (direct costs were 2,091 mln. rub. for naloxone/ oxycodone versus 3,747 mln. rub. for fentanyl TDS). The CER indicator for oxycodone/naloxone was 51 218 rub., while fentanyl TDS had CER of 317 409 rub. BIA revealed considerable budgetary burden reduction for oxycodone/naloxone, which was due to considerable reduction of GDP losses and expenses associated with disability and loss of working capacity. The resultant economy of government funds reached 44%. According to PHe analysis, both drugs are attractive for purposes of drug reimbursement system, but oxycodone/naloxone is dominant due to WTP/CER indicator of 32,1 (fentanyl TDS had WTP/CER of 5,1). Sensitivity analysis confirmed the robustness of these findings - CEA and BIA results remained stable even in case of 25% oxycodone/ naloxone price increase. Conclusion. Oxycodone/naloxone combination has been determined to be most pharmacoeconomically attractive due to higher efficiency of healthcare spending (due to domination in terms of CER) and reduction of GDP losses associated with complete disability which resulted in government budgetary savings of up to 44%.

Rheumatoid arthritis (RA) is a severe, autoimmune disorder characterized by relatively high prevalence among working-age adult population, significant quality of life and work performance impact, as well as high risk of complete disability in case of inadequate or ineffective treatment. The creation of Biologic Disease-modifying anti-rheumatic drugs (bDMARDs) has allowed to significantly improving prognosis for many RA patients, however, the issue of choosing therapy for patients with RA, especially in case of resistance to methotrexate treatment remains problematic, especially in terms of pharmacoeconomic justification of bDMARD choice. Ongoing improvement of clinical understanding of bDMARDs also ensures the significance of further investigating the pharmacoeconomic qualities of these drugs. Aim. To perform the pharmacoeconomic analysis (PHe) of therapy using tocilizumab, adalimumab, as first-line bDMARD therapy in patients with RA receiving standard combination therapy with methotrexate, as well as in patients who require bDMARD monotherapy due to methotrexate resistance, methotrexate nonresponse, or other issues within context of Russian healthcare Methodology. This PHe is conducted from societal perspective which includes interests of Russian healthcare system within context of Obligatory Medical Insurance system and interests of Russian economic system as a whole, including impact on. The time horizon for this research was 2 years. Randomized controlled clinical trials investigating safety and efficacy of these drugs when used in combination with methotrexate and as monotherapy were used as data source on safety and efficacy. A complex PHe model consisting of a «decision tree» (used to form simulated cohorts of patients for each investigated drug, 1 000 simulated patients per cohort) and a Markov model for evaluating treatment outcomes was constructed. Cycle length for the Markov component of the model was 1 week. Clinical improvement of ACR70 was chosen as efficacy end-point because of its high clinical and social relevance. Patients achieving ACR70 can return to workforce. The results of this modelling were used to perform cost-effectiveness analysis (CEA) and budget impact analysis (BIA). Result stability was confirmed by performing sensitivity analyses (SA). Result. During CEA, tocilizumab dominated in terms of cost-effectiveness ratio (CER). CER was 28 525 007 rub. for tocilizumab, 30 898 104 rub. for adalimumab per 1 000 simulated per year in patients receiving standard combination therapy and 21 564 612 rub. for tocilizumab, 30 970 348 rub. for adalimumab per 1 000 simulated per year in patients receiving monotherapy), as well as in terms of clinical effectiveness (as expressed with number of patients achieving ACR70) and with highest healthcare resource utilization effectiveness. BIA indicates that tocilizumab is associated with 4,8% reduction in budget burden compared to adalimumab (estimated per 100 000 per 2 years of Russian population (246 patients), accounted for RA prevalence) in case of standard combination therapy and a 3,98% reduction of budget burden in patients receiving monotherapy. That amounts to 35 575 400 rub. and 28 835 840 rub. respectively (taking into consideration 3,5% discounting factor). SA confirms result robustness to price fluctuations up to 20%.for patients receiving combination therapy and more than 25% for patients receiving monotherapy. Additional sensitivity analysis investigating possible effects of assuming strict safety and efficacy equivalence between the investigated drugs confirms tocilizumab advantage even under such assumption. Conclusion. Modelling results indicate that tocilizumab is pharmacoeconomically rational which is associated with higher effectiveness of healthcare resource utilization. Tocilizumab treatment is also attractive in terms of budget impact as it is associated with up to 4,8% budget burden reduction within scope of 2 years, which is a significant result in context of treating an expensive, potentially debilitating pathology such as RA. Aforementioned results demonstrate that tocilizumab is attractive, pharmacoeconomically effective option for treating patients with in the RF. Prioritization of tocilizumab within context of relevant purchasing channels is thus highly recommended.

The purpose of this literature review is to systematize and synthesis of the available data for the period 20132016 years of pharmacoeconomics evaluation on the application of modern antiplatelet agents in patients with acute coronary syndrome (ACS). Methods. We conduced search in PubMed system and RNITS keywords «pharmacoeconomis and ticagrelor», «cost-effectiveness and ticagrelor», «budget impact analysis and ticagrelor», «analysis and ticagrelor», «pharmacoeconomics and ticagrelor». The review considered approaches to modelling, identifying the main cost and performance criteria. Results. Based on our analysis of published from 2013 to 2016 years literature, it can be concluded that use of ticagrelor instead of clopidogrel in patients with ACS is the dominant technology in the world and Russian practice. The subject of the comparison is most often (81%) spoke of generic clopidogrel and the entire cohort of patients with ACS, without division into tactics of treatment (81%). In the structure of the published studies pharmacoeconomic prevails (95%) temporary retrospective focus of research with a long time horizon (more than 1 year - 88% of foreign studies). In conducting research using Markov modelling in 71% of cases and the analysis of «cost-effectiveness», 52% of researchers, all of them foreign, further analysed the «cost-utility». The cost analysis of 62% of the authors consider only direct medical costs account for 19% of direct medical costs and indirect costs. The main feature is the inclusion of Russian studies in the analysis of indirect costs is that foreign researchers are doing much less (only 17% of researchers). Conclusion. The analysis of pharmacoeconomic studies of ticagrelor can be recommended as a cost-effective method for the treatment of ACS patients, regardless of treatment strategy.

A study of the safety and tolerability tiozonid manufacturing by JSC «Pharm-Sintez» (Russia) at the single dose with it increasing (25, 200, 400 and 600 mg) in healthy volunteers. In each group, the volunteers were enrolled sequentially, based on the interim evaluation of safety parameters. This study was conducted in compliance with the requirements of legislation and the ethical principles set forth in the Federal Law «On Circulation of Medicines» (number 61-FZ of April 12, 2010), the Declaration of Helsinki of the World Medical Association (1964, with subsequent amendments), GOST R 52379-2005 «Good clinical practice» The study drug tiozonid manufacturing by JSC «Pharm-Sintez» (Russia) has shown a sufficiently high safety and well-tolerated at single oral doses in the range of 25-600 mg.

The history of development the ethical and legislative tools for regulation the biomedical research in the states-members of Commonwealth of Independent States (CIS) in the frame of the close collaboration the Forum for Ethics Committees in the Commonwealth of Independent States (FECCIS) and Inter-Parliamentary Assembly CIS (IPA CIS) is demonstrated in this article. The collaboration between FECCIS and IPA CIS stands on the unique experience of IPA CIS in the building of the new, humanistic legislation in the field of health care and on the initiatives of FECCIS to create a single legal space inside and outside of the CIS region. The necessity to promote the dignity, rights, and well-being of human participants in health research was the real reason for creation the Model Law «On the Protection of Human Rights and Dignity in Biomedical Research in the CIS». The process of the law creation, its direction, structure, compliance with international ethical standards and implementation in the local legislation of CIS states are analysed by the main authors of Model Law «On the Protection of Human Rights and Dignity in Biomedical Research in the CIS» and presented in this review.

A serious problem of treatment of infectious disease in preterm infants is the lack of sufficient information on pharmacokinetics of antibiotics in this group of patients. This is due to the insufficient number of clinical trials with premature babies, so in practice is difficult for doctor to choose appropriate antibiotic dose and frequency of dosing him. We have summed up the experience of the American pediatric form NEOFAX, British pediatric form, some clinical trials results and selected the optimal dosing regimen of antibacterial drugs based on gestational and post-conceptual age. This will contribute to safety and efficiency in the treatment of infectious diseases in premature infants caused primarily problematic nosocomial pathogens, such as Acinetobacter spp., Klebsiella pneumonia, Pseudomonas aeruginosa, MRSA, and reduce the risk of adverse drug reactions.

Questions of replacement of original medicines with generic are discussed. The sintesation of identical medicine is a complex challenge from the technological point of view. It is caused by distinctions in production of substances, influence of the variable pharmaceutical factors giving change of the size of particles, a different amorphous forms, a deviation of structure and quantitative content of impurity. Auxiliary substantion characteristics of a production process of ready dosage forms matter. Data on pharmacokinetic equivalence of each generic to original are necessary. For carrying out pharmacotherapy original medicine which receive as a result of the researches executed under the regulated protocol needs data on comparative therapeutic efficiency and shipping the generic of drugs.

Periconceptional folic acid (FA) supplementation for prevention of neural tube defects (NTD) used around 30 years. The effect of FA using for prevention of NTD expected only in case of folate deficiency. The World Health Organization (WHO) identified biomarkers of folate status. The concentrations of serum and red blood cells folate, plasma concentration of homocysteine have potential for therapeutic drug monitoring during FA supplementation. FA should be intake only if it needed clearly in pregnancy. Pregnant women often exceed the tolerable upper intake level of FA. Maternal excessive intake of FA during pregnancy increases risks of epigenetics effects for offspring. The aim of the practical recommendations is to increase awareness among physicians about the most common causes of folate deficiency, the possibility of routine use of biomarkers of folate status, as therapeutic drug monitoring during FA supplementation for prevention of NTD, in accordance with the data of evidence based medicine and WHO guidelines (2015).