Insulin Glargine-300 (GLA-300) is an innovative basal analogue of insulin that has been released into the market in our country and is prescribed to patients with diabetes mellitus (DM). In the real-life practice, GLA-300 is oft en a replacement for the drug of the previous generation - Insulin Glargine-100 (GLA-100) that has been prescribed for more than 10 years and has proved its effi cacy and safety. Government pays for insulins in auctions and tenders, the cost aspects regarding the implementation of GLA-300 in practice are a current problem. According to the aggregated data on patients transferred from GL-100 to GL-300 obtained from the Federal Register of DM of the Russian Federation, the direct costs (DC) for the both types of DM were determined, considering age, complications, and achievement of the target levels of glycated hemoglobin (HbA1c). Th e drugs prices were determined on the basis of the State Register of the Price Ceiling on those medications which are included in the list of the vital and essential medicines (VED). It was found that in case of type 1 diabetes (580 patients), the transfer from GLA-100 to GLA-300 was not accompanied by the transfer from prandial insulin and changes in the total daily dosage of insulins, or HbA1c (59.19 U/day and 59.85 U/day, and HbA1c level was 7.86 % and 7.71 %, respectively). Aft er transferring to GLA-300, the cost of one day of insulin therapy was less by 5.3 %, mainly due to the lower cost of GLA-300 compared to GLA-100 (11.7 % per unit). As for the prandial insulins, insulin aspart (37.4 %) and insulin glulisine (25.5% of prescriptions) were most oft en used. When using GLA-300 + glulisine and GLA-300 + aspart, the levels of HbA1c were similar: 7.71 ± 0.44 % and 7.64 ± 0.48 %, respectively (p< 0.05). Th e cost minimization analysis (CMA) showed the economy cut of 4.5 rubles/day on average when using GLA-300 + insulin glulisine in comparison with GLA-300 + insulin aspart. In type 2 diabetes, 331 patients received monotherapy and 494 patients were given basal + and basal-bolus treatment. In case of monotherapy, daily doses of GLA-100 and GLA-300 did not statistically diff er in both the general study population and in subgroups of patients with and without complications (29.80 U and 30.90 U; 25.61 U and 26.91 U; 30.71 U and 31.63 U, respectively). At the same time, there were no changes in HbA1c levels before and aft er the transfer. CMA showed the reduction in treatment costs by 8.4% when transferring to GLA-300 in the general population and by 9.0% in the group of patients with complications. Th e same dosages of 30.4 U/day of GLA-100 and GLA-300 were used in 42.9% of cases with similar HbA1c levels (7.42 ± 0.33% and 7.42 ± 0.41%, respectively), before and aft er the transfer, and the economy cut upon transferring to GLA-300 in this case amounted to 277.4 thousand rubles/year/100 patients. Th ere were 242 patients aged >60 years (73.1 %). Th e costs of using GLA-300 in this population were 5.2% lower than those when using GLA-100. In a subgroup of patients with complications who reached the target level of HbA1c (153 patients), the dosage of GLA-300 was higher by 1.58 U/day, but the costs for using GLA-300 were 7.2 % lower than those for the therapy with GLA-100. Th e costs for using basal + and basal-bolus schemes in type 2 diabetes decreased by 7.1% aft er the transfer, mainly due to the lower cost of GLA-300 with practically equal dosages of insulins before and aft er the transfer. Conclusion: Th e transfer from GLA-100 to GLA-300 in patients with both types of DM in real-life practice of prescribing these drugs does not require increased dosages, is not accompanied by any changes in HbA1c level, and reduces the direct costs on insulin therapy.

Rationale. There is a certain variability of endpoints in diabetes pharmacoeconomic research in Russia. It makes difficult to compare the economical effectiveness of hypoglycemic drugs. Aim. To estimate a proportion of final and surrogate endpoints used as effectiveness criteria in pharmacoeconomic studies of hypoglycemic drugs proposed for inclusion into the Russian essential drug list in 2014-2016. Methods. 22 pharmacoeconomic studies on 12 hypoglycemic drugs were reviewed. Results. 8 effectiveness criteria were analyzed. Four of them (50%) were final endpoints. 26 of 41 outcomes (63%) related to final endpoints. The most often used endpoint was quality adjusted life years (QALY) - 62% of all final outcomes. The number of avoided cardiovascular events was another commonly used final endpoint (31 % of all hard outcomes). Change in glycated hemoglobin level was the most often used surrogate endpoint (73% of all surrogate outcomes). Conclusions. 1. At least one final endpoint was used in 19 of 20 studies (95%). 2. The most commonly used final endpoints are QALYs and the number of avoided cardiovascular events (93% of all hard outcomes). 3. Glycated hemoglobin level should not be used as the main effectiveness criteria determining the inclusion of drugs into the essential drug list.

Over the past several decades, adaptive design methods in clinical trials has become more popular as a way to increase the efficiency of the early and late phases of clinical development by means of reducing costs, resources and duration as well as increasing the likelihood of trial success and the chance for patients of being allocated to the treatment that’s more effective and safe. The following prospectively planned modifications can be implemented in an adaptive study: eligibility criteria, sample size and/or study duration, randomization procedure, treatment regimens, including the number of treatment groups, concomitant medication, patient evaluation schedule, endpoints, statistical methods. Opportunity to change some elements of the design based on interim results during the course of the study provides advantages over the traditional fixed design. Nevertheless, the implementation of adaptive designs is more complex, such trials require more thorough planning, and are often accompanied with various degrees of statistical, procedural, logistic and regulatory issues. The aim of this article is to provide the main definitions, to highlight the pros, cons of adaptive design at different phases of drug development from statistical and regulatory point of view for better understanding of the methodology.

The article presents the new possibilities of preventing the onset of irreversible myocardial damage during ischemia and effective approaches undertaken in the early reperfusion period (per - and postconditioning of the myocardium) through coronary the introduction of cardioprotective drugs. Practitioners need medicines, which have fewer complications and are universal this is by far the metabolic drugs. The author surveyed 300 patients (three groups) with acute coronary syndrome (ACS) hospitalized no later than 4 hours from the beginning of anginal attack. Patients in group I (n=109) in the prehospital phase was carried out by the system tromboliticescoy therapy (TLT) in combination with intravenous etilmetilgidroksipiridina succinate (200 mg), which the hospital performed mechanical recanalization and angioplasty of the infarct-related coronary artery (IRA) with intracoronary introduction of etilmetilgidroksipiridina succinate (200 mg). Patients in group II (n=101) etilmetilgidroksipiridina succinate (200 mg) primary intracoronary injected during the endovascular procedure. Patients III (control) group (n=90) was carried out only angioplasty of the IRA. Conclusions: the effect of restoration of coronary circulation set after conducted thrombolytic therapy with intracoronary administration of etilmetilgidroksipiridina succinate immediately after successful angioplasty of the IRA, which helped to restore adequate blood flow to prevent relapses and extension of the necrosis zone, transition to a higher angina functional classes.

This article is about the efficiency of web based systems for pharmacovigilance (PV) processes management in connection with pharmacovigilance signals based on case study of the implementation of Flex Databases PV system. It describes principles of signals management, provides analyses of modern methods of signal management (quality and quantity), and also describes perspective methods of signals management. The article highlights the importance of signal management in pharmacovigilance as an obligatory process for all companies-holders of registration certificate and investigation companies in all EAEU member states, including Russia.

Purpose. To study the structure of serious adverse drug reactions and «off label» drug use in children by means of analysis of the national pharmacovigilance database. Materials and methods. We analyzed 341 spontaneous reports about serious adverse reactions in children, submitted to the Russian pharmacovigilance database in 2012, and 467 suchlike spontaneous reports registered in 2015. Results. Children of preschool age have higher risk of medical therapy complications. Most frequently, skin (33,4% in 2012 and 38,7% in 2015) and organism as a whole (21,4 and 21,1%, respectively) were involved in the pathological process. Antimicrobial drugs for systemic use (43,5% in 2012 and 43,8% in 2015) and drugs for nervous system (25,1 and 26,1% respectively) often caused them. Unexpected serious adverse reactions accounted for 16,9% of all complications in children in 2012, 10,8% in 2015. It was established that 58,7% of suspected medicines in 2012 and 47,5% in 2015, the use of which was associated with the development of serious complications in pharmacotherapy in children, were prescribed with deviations from the recommendations of approved prescribing drug information. The main types of «off-label» drug use were inappropriate indications, deviations from the recommended dosage regimen, the use of a drug in the age group of patients, wherein the drug has not been approved, and the use of a drug in the presence of contraindications to its use. Conclusion. Our research confirms that the practice of «off-label» drug use in children is an independent risk factor for developing adverse drug reactions. It is shown that the method of spontaneous reporting can help to identify the problems of drug safety and to develop recommendations for minimizing the risk of complications of pharmacotherapy in pediatric practice.

Practical approaches to use of oral anticoagulants for prevention and treatment of thrombotic and thromboembolic complications in patients with atrial fibrillation, venous thromboembolism and coronary heart disease are considered. Comparison of main pharmacologic properties of DOACs and warfarin as well as their efficacy and safety in prospective randomized controlled trials are present. Clinical situations with minimal or no evidence for use of DOACs are specified.

The results of fundamental and clinical studies show the importance of providing males with vitamin D in order to (1) assist the formation of the testicles, (2) maintain the steroid-synthesizing and other functions of the testicles, (3) maintain the functioning of the spermatozoa and, in general, maintain the male fertility.

The training manual «Clinical project management» describes a methodology for the effective management of a clinical project for finding, developing and marketing pharmaceuticals products, starting with the search for new chemical compounds, preclinical testing of candidate substances, clinical trials of candidate in drugs, pharmacovigilance, data management, analysis of the data, drafting the final study report, obtaining registration certificate, quality assurance of trials, publication the results, ending with the organization of post-authorization safety studies, conducting non-interventional and pharmacoepidemiological studies, audit and inspection of regulatory authorities, creating standard operating procedures and archiving research documents. The material is based on modern Russian Federation and Eurasian Economic Union regulations. The manual is addressed to those who are directly involved in the development of new drugs: clinical project managers, clinical research associates, specialist in pharmacovigilance, data management, statistical analysis, quality assurance and control, registration, representatives of regulatory and medical departments, medical writers, working in innovative pharmaceutical companies and contract research organizations. Presented materials will also be useful to investigators, employees in research institutes and organizations involved in the search of new molecular entities, preclinical and clinical trials, and to the health authorities, that regulate their conduct.