The training manual «Clinical project management»

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

Evidence-based medicine: new in the search for evidence

The review is focused on discussing new trends in DM, rethinking the evidence base medicine with an emphasis on demonstrating the efficacy and safety of new therapeutic agents and medical technologies, from gene editing to AI algorithms. At the same time, clinical trials of drugs are also not standing still, there is active development, new approaches, methods and designs are being developed. The process of drug development, registration and market launch of any drug takes a significant period of time, requires high financial costs and human resources. The gold standard of evidence-based medicine was initially considered to be RCTs, but at the same time, they have objective disadvantages: limited sample, inability to control all factors; insufficient follow-up time,negative impact on participants, inability to determine cause-and-effect relationships; limited measurement methods, limited budget and others. This review discusses the trends in the methodology of clinical research. The active implementation of new designs such as Adaptive Clinical Trials, "Master" protocols including Umbrella Study, Basket Study, Platform Studies, Master Observational Trials and the increased use of Single Patient Trials (N-of-1 trials) are allowing studies to become more efficient, relevant and applicable to real-life health care practice settings and patient-centered. In the review, we also look at both the pros and cons of the expanded use of biomarkers and Digital Endpoints in clinical trials and virtual clinical trials, which use mathematical models to study patient heterogeneity and its impact on various therapeutic questions. The process of expertise and regulatory approval continues to slow down the entry of drugs into the pharmaceutical market. The review considers changes in the approaches of regulators (FDA, EMEA and Russian Ministry of Health) to the drug registration procedure. The COVID-19 pandemic and sanctions have led to the need to expand the list of drugs with authorized accelerated registration. However, accelerated registration raises many questions regarding the sufficiency of the level of evidence and safety. As we can see a deep synthesis and integration of all available data is needed to achieve the next generation of evidence-based medicine. The major challenge in the next two decades will be to exploit the potential of multidimensional evidence generation by extracting, collating and generating large data sets of natural course of disease, genomics and all other omics analyses, all published clinical trials, RWD to provide next generation evidence

Review of real-world data study

The article defines the terms «real-world data» (RWD) and «real-world evidence» (RWE); classification of RWD, advantages, disadvantages and their overcoming are outlined; provides a description of the purpose of collecting RWD

Pharmacoeconomic analysis of trastuzumab emtanzine comparing to lapatinib + capecitabine in pa-tients with HER2+ breast cancer and central nervous system metastases

Aim. To perform health-economic evaluation of trastuzumab emtansine (T-DM1) in patients with HER2+ breast cancer and CNS metastases. Materials and methods. Cost-effectiveness analysis along with sensitivity analysis and budget impact analysis were performed. Direct medical costs and indirect costs (GDP loss) were accounted. Results. At 3 years modeling horizon total cost of trastuzumab emtanzine were higher comparing to lapatinib+capecitabine due to significantly higher overall survival (OS) observed in trastuzumab emtanzine group. CER OS for T-DM1 and lapatinib+capecitabine were 1 686 222 RUR/patient/ year and 1 704 486 RUR/patient/year, consequently. T-DM1 ICER (OS) was lower than cost-effectiveness threshold in Russia in 2016. Conclusions. The study showed T-DM1 is a cost-effective strategy in patient with HER2+ metastatic BC and CNS metastases

Pharmacovigilance system in Eurasian Economic Union

The article deals with the main provisions of the basic document — «Rules of good practice of pharmacovigilance of the Eurasian economic Union», which regulates the study and prevention of adverse reactions and other problems associated with drugs in the member States of the Union, including the Russian Federation. Also, the Rules establish requirements for the organization of pharmacovigilance system in pharmaceutical companies, detail the work of manufacturers in the field of risk management, as well as determine the procedure for informing employees of the pharmaceutical industry and specialists of medical institutions of the authorized bodies about the identified safety problems in the use of medicines

Legal aspects of conducting real-world studies

The article describes the modern legal aspects of conducting research on real clinical practice both in the European Union and United States of America, as well as in Russia and EAEU member states

Socio-economic burden of COVID-19 in the Russian Federation

Purpose. Assessment of the socio-economic burden of COVID-19 in the Russian Federation (RF). Materials and methods. Identification and assessment of direct medical, direct non-medical costs, as well as indirect costs associated with the development of the coronavirus infection epidemic. When calculating the socio-economic burden, the prevalence-based calculation approach was chosen. The sources of data on the epidemiology of the disease were data from the Ministry of Health and data from the Government of the Russian Federation. Results. The socio-economic burden of COVID-19 in the Russian Federation will amount to 4.6 trillion rubles ($71.1 billion) or 4 % from GDP. In the cost structure, more than half of the costs are direct non-medical expenses (58.62 %), indirect expenses due to GDP losses are 40.65 %, direct medical expenses are only less than 1 % (0.74 %). The results of the sensitivity analysis showed that the extension of the self-isolation period from 1 month to 1.5 and 2 months will lead to an increase in the share of indirect expenses from 40.65 % (1 month) to 56.08 (1.5 months) and 67.76 % (2 months) for all expenses in connection with the COVID-19 epidemic. At the same time, the socio-economic burden of COVID-19 will amount to 6.2 and 8.5 trillion rubles, respectively. Conclusions. The epidemic of a novel coronavirus infection will lead to great economic losses in the Russian society

GCP inspection by Roszdravnadzor

State institutions determine the rules for conducting clinical trials of drugs; therefore, they must directly monitor their conduct. The main form of control over clinical trials of drugs by the state is the inspection. This is article describes the types of inspections, the main identified violations, proposed further actions and consequences

Baikal-GVD: status and prospects

Baikal-GVD is a next generation, kilometer-scale neutrino telescope under construction in Lake Baikal. It is designed to detect astrophysical neutrino fluxes at energies from a few TeV up to 100 PeV. GVD is formed by multi-megaton subarrays (clusters). The array construction started in 2015 by deployment of a reduced-size demonstration cluster named "Dubna". The first cluster in its baseline configuration was deployed in 2016, the second in 2017 and the third in 2018. The full scale GVD will be an array of ~10000 light sensors with an instrumented volume of about 2 cubic km. The first phase (GVD-1) is planned to be completed by 2020-2021. It will comprise 8 clusters with 2304 light sensors in total. We describe the design of Baikal-GVD and present selected results obtained in 2015-2017.Comment: 9 pages, 8 figures. Conference proceedings for QUARKS201