This issue of the journal includes articles on clinical-economic expertise of new drugs and the problem of clinical studies of early phases on healthy volunteers.

On the basis of multicriteria analysis, a pilot complex system for evaluating medicinal products (MP) used in the therapy of oncohematological diseases has been developed. The obtained results allow to rank MPs by priority of choice when making decisions on procurement of drugs or inclusion in MP lists in the framework of programs of preferential drug provision of the population. It has been shown that, according to the set of criteria, ibrutinib in treatment of chronic lymphocytic leukemia (CLL) has the highest priority, followed by obinutuzumab (CLL treatment) and ruxolitinib (treatment of myelofibrosis).

The high prevalence of BRAF V600 gene mutation in the Russian Federation and the cost of treatment the metastatic melanoma (MM) with immuno-oncology and combined targeted drugs make it relevant to assess the clinical and economic feasibility of their use. Objective. Cost-effectiveness analysis (CEA) and budget impact analysis (BIA) of PD-1 inhibitor pembrolizumab was performed in comparison with nivolumab and combinations of BRAF and MEK inhibitors in the 1st line therapy of MM with BRAF v600 gene mutation. Methodology. CEA and BIA was performed using the results of a network meta-analysis and based on the Markov model, which estimated the number of life years saved (LYS), duration of progression-free survival and direct medical costs (DC). Results. The cost of treatment per year in the 1st line therapy on pembrolizumab was 3.32 million RUB, what is 29 % cheaper than combination of dabrafenib + trametinib (4.67 million RUB), 60 % than vemurafenib + cobimetinib (8.30 million RUB), 1.7 % than nivolumab (3.38 million RUB). Total 3 years DC for the 1st line therapy on pembrolizumab (3.80 million RUB) were 43.9%, 68.2% and 1.8 % lower than the cost of dabrafenib + trametinib (6.76 million RUB), vemurafenib + cobimetinib (11.93 million RUB) and nivolumab (3.86 million RUB). CER per 1 LYS for pembrolizumab was 2.43 million RUB, nivolumab – 2.48 million RUB, dabrafenib + trametinib – 4.24 million RUB and vemurafenib + cobimetinib – 7.49 million RUB increase in the use of pembrolizumab to 50 %, by reducing the share of the use of combinations of BRAF and MEK inhibitors, will result in budget savings up to 1 507,5 million RUB (26.4 %). Conclusion. The use of pembrolizumab in the 1st line of MM therapy with BRAF V600 gene mutation allows to save the budget and is economically feasible.

Aim. To analyze the efficacy, safety and pharmacoeconomic indicators of ocrelizumab in adult patients with primary progressive multiple sclerosis (PPMS). Methods. An information search was conducted in the databases Embase, PubMed, Cochrane and eLibrary.ru. The levels of evidence were determined in the studies. Results. Therapy with ocrelizumab compared with placebo characterized by a decrease in the rate of progression of the disease. Treatment with ocrelizumab was associated with a significant slowdown in progression compared to other drugs: rituximab, fingolimod, myelin basic protein peptide 82–98, intravenous immunoglobulin; plasmapheresis / plasma metabolism, corticosteroids, general irradiation of lymphoid tissue, and other most common adverse events: infusion reactions, nasopharyngitis, upper tract respiratory and urinary tract infections, headaches. Life years and quality-adjusted life years for patients receiving ocrelizumab were 16.11 and 3.33, compared with 15.61 and 2.75 for patients receiving better supportive care, respectively. The annual average potential impact on the budget for 1 patient with PPMS in the treatment of ocrelizumab for 5 years ranged from $ 18,300 to 44 200. Conclusions. Ocrelizumab is the only drug that has proven its clinical efficacy in the previously non-curable type of multiple sclerosis, PPC, with risk profile acceptable with respect to clinical benefits.

Purpose. Comparative economic analysis of complex rehabilitation of children with cerebral palsy (CP) with and without injections of botulinum neurotoxin type A (Dysport®, BoNT-A). Materials and methods. We clinically followed up 149 children with spastic forms of cerebral palsy (GMFCS II-IV) – 78 boys and 71 girls in the age period from 2 to 14 years (108 children who received intramuscular BoNT-A injections and 41 children who underwent similar complex treatment without it). In the budget impact analysis (BIA) only direct medical costs were taken: the cost of pharmacotherapy BoNT-A, rehabilitation care and surgery. Results. Children with CP of the main group needed surgical correction for the first time by 10.5±2.8 years, 4.6 % (5 children) of them needed repeated 95 % (39 children) of the comparison group during the period of active growth from 10 to 12 years. As a result, the BIA found that the use of the treatment scheme for children with CP using abobotulinumtoxinA will save the budget of 24 744 690 RUB per 100 children compared to standard therapy for 12 years of observation. During the CEA it was found that to achieve 1 % efficiency in children with CP with the use of abobotulinumtoxin A requires 1 854 426 RUB, and to achieve a similar result without BoNT-A — 40 702 271 RUB. Including abobotulinumtoxinA injections in the comprehensive rehabilitation of children with CP would allow to treat additional 14 % children (compared to a treatment without BoNT-A ) with the same budget. Conclusion. It was found that the use of treatment regimens for children with cerebral palsy using the BoNT-A is economically justified. Long-term therapy of children with CP with Dysport® during a 12-year-follow-up has considerably improved clinical outcomes and could provide a saving of 24 744 690 rubles compared with a standard therapy per 100 patients. Considering the register of children with CP in the Tyumen region on 01 January, 2018, the budget savings could account for 5,938,726 rubles a year.

This article reviews perspective of the targeted radionuclide therapy (TRT) as one of the rapidly growing fields of nuclear medicine. The characteristics, features of action, advantages and disadvantages of the most used α- and β-emitters (223Ra, 213Bi, 225Ac, 211At, 89Sr, 90Y, 131I, 153Sm, 177Lu) are presented. New approaches based on the use of α-emitting isotopes in the treatment of castration-resistant prostate cancer with bone metastases, acute myeloid leukemia, melanoma, neuroendocrine tumors, and brain tumors are discussed. The importance of TRT in routine clinical practice is underlined. The use of targeted radionuclide therapy in clinical settings in our country should be expanded

This article discusses important problem of early phase clinical trials – over-volunteering. The overlapping or dual enrollment of healthy volunteers is a potential high risk not only to study subjects, but also to commercial sponsors because it could cause the delay in advancement of promising drug candidates. The problem of over-volunteering is payed special attention by clinical research professionals in foreign countries. Guidelines for early phase clinical trials recommend implementation of different control and prevention measures of multiple enrollment. The most effective instrument to prevent over-volunteering is considered to be a central internet-based registry of healthy volunteers. Such registries operate in various countries and differ in structure, scope of information collected, types of funding and management. The general operating principles of such registries are described on the example of TOPS data base. TOPS is а special system to prevent over-volunteering that is used by UK phase 1 units. In conclusion, authors urge regulatory authorities and pharmaceutical companies to approach this problem closely because over-volunteering is already a burning issue in our country. It is essential to improve relevant regulatory framework and launch central registries of healthy subjects with regard to international experience.

This article discusses one of the most disputable issues in national clinical research practice in healthy volunteers. Regulatory requirements forbid to assess even minor deviations of laboratory parameters from reference intervals as not clinically significant. Authors made analysis of such requirements from positions of foreign and national guidelines of early phase clinical research and with regard to their own experience in the field. As an important part of this work, retrospective analysis of the laboratory test results data of healthy volunteers taken from several clinical trials was conducted. The aim of this analysis was to establish the rate of not clinically significant deviations from reference intervals. The results of the analysis revealed rather high rate of not clinically significant deviations of some laboratory parameters from reference intervals in volunteers with confirmed status “healthy”. Authors noted that developers of clinical trial protocols have no unified approach to generate list of necessary laboratory tests and methods of assessment of the results. Ethical and financial aspects of the problem under discussion are also touched in this article. In conclusion, authors suggest the scale of clinical significance assessment of deviations of basic laboratory parameters from reference intervals as one of the possible options of optimizing current regulatory requirements.