Second generation insulin analogue — insulin glargine 300 UI/ml (GLA-300) — can provide an effective control of Diabetes Mellitus (DM) with minimal risk of hypoglycemic events and prevent of cardiovascular complications or events (CVS). Pharmacoeconomic comparison of most used insulins — GLA-300 and detemir (IDet) has been based on indirect treatment comparison in DM Type 2.
Materials and methods. Indirect treatment comparison was created according to published data of a real world evidence data for the treatment of DM Type 2 with GLA-300 and IDet, and common comparator — GLA-100 — has been used. Patients (%) who reached HbA1c target were indicated as an efficacy criteria. Odds ratios (OR) were calculated for clinical efficacy and severe hypoglycemia’s rate comparisons for GLA-300 and IDet. Direct (cost of annual treatment, hypoglycemia correction, CVS treatment), indirect medical costs as well as indirect costs (GDP loses) were calculated for GLA-300 and IDet strategies. Sensitivity analysis has been performed for confirmation of the base scenario results.
Results. GLA-300 has advantages vs IDet by efficacy and less risks of severe hypoglycemia (OR 1.27 CI 95 % 1.02; 1.58 and OR 0.72 CI 95 % 0.56; 0.88 accordingly). Probability of good control of DM Type 2 (based on target of HbA1c<7.0 %) was higher on 27 % in GLA-300. Costs of insulins, expenditures for CVS treatment and payment for temporary disability were similar for GLA-300 and IDet groups (for the one-year treatment period), in the same time in GLA-300 group the less expenditures for hypoglycemia were observed. Total expenditures were slightly less for GLA-300 on 3.7 % vs IDet.
Conclusion. GLA-300 and IDet have no economic advantages between groups in total costs, but GLA-300 has tended for economic benefi ts in compare with IDet in DM Type 2.

The prevalence of comorbidity — asthma and atopic dermatitis — is not understood well yet. More severe processes decreasing quality of life and increasing a social-economic burden of disease are occurred in such kind comorbidity.

Aim: an evaluation of economic burden of non-control severe asthma in combination with severe atopic dermatitis in the local conditions.

Materials and methods. Analysis has been performed for adult patients; the bottom-up approach of costs evaluation was used. Direct medical and non-medical as well as indirect costs were calculated for two models: Model 1 — current practice of the treatment, Model 2 — treatment with Dupilumab.

Results. Model 1 — Weighted average expenditures for one patient were 3,1 mln RUR, indirect costs were dominated (76 % from the total), severe atopic dermatitis had 15 % of total. Model 2 (with Dupilumab) — Dupilumab has decreased the total weighted average cost on 903 905 RUR. The total economic burden of comorbidity was 17,6 bln RUR in the current treatment option, and 12,4 bln RUR in Dupilumab hand (different is 5,2 bln RUR, or burden decrease is expected on 29,2 %).

Conclusion. The wider introduction of Dupilumab into clinical practice, which allows achieving control in the treatment of severe asthma and severe atopic dermatitis, should reduce treatment costs and reduce the socio-economic burden of these diseases as a result.

The Government Decree, approved in December 2019, required registration certificates holders of reference drugs, included in the essential drug list (EDL), submit applications for mandatory price re-registration. Drugs included in the high-cost nosology list (high-cost list) must be included in the EDL.

Objective: to assess the budget impact of price re-registration for high-cost list drugs.

Material and methods. The comparing economic analysis of high-cost nosology program before and after price re-registration based on the Government Decree N 1683 (effective from 16.12.2019). 125 reference stock keeping units (SKUs), included in the high-cost list, were evaluated.

Results. The analysis showed, that after re-registration the prices of 66 SKUs will remain the same. The prices of 43 reference SKUs will be reduced after setting a single maximum selling price («equalization»). Prices for 16 SKUs will be reduced due to lower registered prices in the reference countries. Considering the contracts executed in 20192020, the budget of the high-cost program is up to 74.430 billion rubles, and after re-registration it will be equal to 64.162 billion rubles, so the savings will amount 10.267 billion (13.8 %). The main drivers of re-registration prices savings are: Advagraf (1.175 billion rubles), Elizaria (2.083 billion rubles) and Revlimid (2.247 billion rubles). Separately, we analyzed the consequences ofprices re-registration in the V-thgroup ofhigh-cost list, which are provided topatients with malignant neoplasms of lymphoid, hematopoietic and related tissues. It was calculated, that in 2019 the contracts for V-th group of high-cost list were signed for 19.217 billion rubles, and after the price re-registration for the purchase of the same number of drugs 16.762 billion rubles will be spent, so the savings from the price re-registration will amount to 2.455 billion rubles (12.8 %), among which 2.247 billion rubles will be provided by price re-registration of Revlimid.

Conclusions. The pricing policy implemented in the Russian Federation is aimed at increasing the availability of highly effective medical care to the population of the Russian Federation and significantly reduces the burden on the budget of the healthcare system.

The aim of the study consisted in assessing the long-term effectiveness of the drug in the treatment of chronic disease based on Markov modeling (on the example of the use of roflumilast in the treatment of chronic obstructive pulmonary disease).

Materials and methods. The data on the dependence of exacerbations on the stage of COPD from the ECLIPSE study (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) were used as materials for the study. The simulation was carried out using MO Excel software based on the Markov model. The input data were 1 000 patients with COPD II stage. The time horizon was 10 years. The Markov cycle was 1 year. Additional patients were not included in the model and did not drop out during the simulation.

Results. The number of patients with stage IV for the last modeling cycle (10 years) will be 265 patients with the addition of roflumilast to COPD, then without roflumilast, this figure will be 296 patients. The addition of roflumilast to COPD therapy slows the transition to stage IV COPD by 10.5 % for 10 years.

The conclusion. The Markov model of the transition of patients suffering from COPD through stages of the disease characterizes the course of the disease on the time horizon at 10 years. Of the model group of 1000 patients (suffering from stage II COPD), only 48.4 % of patients remain in this stage at the end of the simulation. On the last cycle of the modeling time horizon, in stage III there are 22.1% of the initial cohort of patients, in stage IV — 29.6 %. ttese data reflect actual clinical practice. When modeling using the frequencies of transitions between states obtained during studies in which the efficacy of adding roflumilast, inhibitor of PDE-4 to treatment regimens was studied, modeling slowed down the progression of the disease.

Aim. To assess the pharmacoeconomic feasibility of including the drug upadacitinib in restrictive lists and government funding programs to provide patients with rheumatoid arthritis.

Materials and methods. Study Design — Retrospective Analysisof Literary Data. Pharmacoeconomic analysis methods — indirect comparison, clinical-economic analysis (cost-effectiveness analysis) using sensitivity analysis; budget impact analysis using sensitivity analysis. Data on the effectiveness of the analyzed drugs are taken from publications on clinical studies of the compared drugs; on the cost of drugs — the state register of marginal selling prices, data of the manufacturer’s company.

Results. According to the results of indirect comparison, with respect to the frequency of achievement of the DAS28 test (CRP) <2.6, the effectiveness of the preparations tofacitinib and baricitinib does not significantly differ — OR = 1.275 (0.842; 1.931). At the same time, the preparation upadacitinib allows to achieve this indicator reliably more effective than the baricitinib — OR = 1.529 (1.021; 2.292) and tofacitinib — OR = 1.95 (1.285; 2.960). Costs for the use of upadacitinib against the background of methotrexate for 52 weeks will amount to 654 983.88 rubles, and will require 4.7 % less costs than the use of tofacitinib or baricitinib against the background of the use of methotrexate (687 217.53 rubles). In an indirect comparison of upadacitinib-baricitinib through the general comparator adalimumab, the effectiveness of upadacitinib with respect to the frequency of achievement of DAS28-CRP <2.6 turned out to be higher than baricitinib per 32.3 %. With indirect comparison of upadacitinib-tofacitinib under the same conditions, the efficiency of upadacitinib is 57.7 % higher than that of tofacitinib. Analysis of the impact on the budget showed that with the inclusion of the drug upadacitinib in the lists of VED and ONLS and a gradual increase in the proportion of patients, receiving upadacitinib instead of tofacitinib and baricitinib in the 1st year before 15 %, in the 2nd year — 30 %, in the 3rd year — 45 % for the group of 2.318 patients for 3 years, the reduction in the budget burden will be 1.4 % or 62.8 million rubles. With the provision of upadacitinib, 100 % of patients from the first year, the budget burden for 3 years will decrease by 4.7 % or 213.1 million rubles in comparison with the current regime.

Conclusion. tte drug upadacitinib at a lower course cost has greater effectiveness in achieving clinical remission according to the indicator DAS28-CRP (<2.6), and therefore its use in the conditions of the healthcare system of the Russian Federation for the treatment of patients with rheumatoid arthritis is pharmacoeconomic and expedient.

Pragmatic clinical trials (PCTs) allow combining the advantages of observational trials in real-world evidence with the scientific rigor of randomized clinical trials (RCTs), and thereby provide more effective answers to questions of real-world evidence.

Aim. Assessment of differences in conducting RCTs and PCTs, as well as analysis of the features related to conducting PCTs at different stages.

Methods. An analysis of publications in the period from 1999 to 2017 was conducted to identify data on PCTs.

Results. There are significant differences in conducting classic RCTs and PCTs. First, PCTs use more flexible inclusion criteria and differ in the approach to choosing an investigator’s site. Also, the procedure for obtaining informed consent has significant differences from that of classical RCTs; alternative options are proposed but a unified approach has not yet been developed. When conducting PCTs, monitor intervention should be minimal in order not to interfere in the routine therapy, which, however, can lead to a violation of reporting. A possible solution may be remote data collection.

Conclusion. PCTs represent a huge potential for studying the effectiveness of drugs in real-world evidence. However, despite a significant increase in the number of such trials, there are still a sufficient number of points that need to be resolved.

The liver is the main organ responsible for the biotransformation and elimination of drugs, and therefore its function is often impaired by different medications. In this article, the authors inform practical health care professionals about the possible liver damage with cholestasis caused by drugs (DILI). Most often, DILI is caused some antibacterial drugs, steroids, barbiturates and some other drugs. DILI has no pathognomonic clinical manifestations. tte scientific literature describes both an asymptomatic increase of “liver” enzymes and the development of acute liver failure. Important diagnostic methods are the collection of anamnesis (especially the medicinal one), analysis of blood biochemical tests, and data from visual diagnostic methods. If the patient has DILI, it is necessary, whenever possible, to stop intake of a drug. ttere are no specific drugs recommended for pharmacotherapy of DILI but there is some the positive effect of ademetionine and ursodeoxycholic acid. ttere are no specific preventive measures for DILI. Healthcare practitioners are recommended not to use drugs off-label, optimize pharmacotherapy and fight with polypharmacy, monitore biochemical tests regularly etc.

The article emphasizes the need to develop and apply standard operating procedures (SOP) as an instrument of quality management system of rational pharmacotherapy in primary care practice. To justify the reasonability of SOP implementation into outpatient clinical practice pharmacoepidemiologic analysis of the quality of care provided to patients with stable coronary artery disease in the primary care setting of Moscow over two consecutive periods was used. tte key variables of interest were characteristics that reflected physician adherence to clinical practice guidelines.

Actuality. Drug safety issues in patients with psychiatric disorders are relevant due to specifics of clinical pharmacology of the medicinal products used, possible treatment-resistance of mental illnesses and concomitant use of multiple antipsychotic drugs. One of the aspects of treatment safety is a prediction of drug-drug interactions.

The aim of the study was to analyze potential drug-drug interactions in patients with psychiatric disorders.

Materials and methods. The study enrolled 500 patients with psychiatric disorders in two age-related groups. Drug therapy was analyzed to reveal potential cases of drug-drug interactions.

Results. A total of 1 031 cases of the use of drug combinations leading to drug-drug interactions of various clinical significance were revealed in 72.4 % of patients. There were significant differences between two age-related groups in respect of the specifics of medications use and clinical significance of drug combinations.

Conclusion. Prediction of drug-drug interactions is likely to ensure improved drug safety in patients with psychiatric disorders.

The rational prescription of medicines with preferential drugs provision, including nootropics, which are widely used in patients receiving pharmacotherapy under the «Program for Providing Certain Categories of Citizens with Necessary Drugs», is possible only if modern evidence is available.

Aim. Conduct information content of the «Database of Clinical Trials of Medicines» for relevant in preferential drugs provision: cerebrolysin there is no international non-proprietary name; piracetam; livestock cortex polypeptides; citicoline and create recommendations on the use of nootropics.

Materials and methods. Search and analysis of the results of clinical trials, systematic Reviews and meta-analysis was carried out in the international databases PubMed, EMBASE, Cochrane Collaboration, followed by entering into the electronic resource «Database of Clinical Trials of Medicines» for nootropics.

Results. Nootropics have a positive effect mainly on the studied «surrogate» outcomes (improving the clinical condition of patients), without significantly affecting clinical outcomes (reducing the number of adverse outcomes and mortality) in severe neurological pathology.

Conclusion. Service «Database of Clinical Trials of Drugs» for use by healthcare professionals and recommendations on the use of nootropics can apply for rational drugs prescription in preferential drugs provision.