Launch speed: why Moscow created a drug research ecosystem

How the program works, which at one time contributed to the rapid entry into the market of the world's first vaccine against covid-19 , and what opportunities it gives market participants - in the material of RBC

Moscow has created a large-scale ecosystem for conducting clinical drug trials. Its development will speed up the introduction of innovative drugs to the Russian market and provide them to residents throughout the country. For the first time, the system was successfully tested as part of a study of the world's first vaccine against COVID-19. It is expected that it will support domestic pharmaceutical manufacturers and accelerate import substitution.

According to Moscow Mayor Sergei Sobyanin, the capital has been a leader in clinical trials in RUSSIA for more than 20 years. “Over the past three years alone, metropolitan doctors have conducted more than 500 trials of new drugs - in the context of import substitution, an extremely important figure,” he noted in his TELEGRAM .

“We continue to support the pharmaceutical industry so that the residents of the capital always have access to all the necessary drugs, and we are confident in the quality and effectiveness of medicines,” said Anastasia Rakova, Moscow Vice Mayor for Social Development. — We are already cooperating with ten pharmaceutical companies, each of which develops its own line of drugs and conducts several studies at the same time. Recently, the number of clinical trials planned and already successfully launched at our medical institutions has more than doubled. This is already 31 studies in 22 nosologies, including oncology, endocrinology, cardiology, pulmonology, hematology and surgery.”

According to the vice-mayor, research centers based in Moscow hospitals and polyclinics have already been selected for 14 studies, and the selection process for five more is currently underway. Volunteer recruitment assistance was provided for two studies, and deployed patient databases are being prepared for nine studies to further assist in recruitment. In addition to organizational support measures, the Moscow government also provides financial assistance in clinical trials of drugs that are relevant for the capital's healthcare system. Two pharmaceutical companies have already applied for financial support for ten studies. Of these, for six studies, companies applied for not only financial support, but also organizational support.

Laboratory on the basis of the State Clinical Hospital named after S.P. Botkin (Photo: press service of the Moscow Social Development Complex)

Clinical trials are a common practice for bringing any drug to the pharmaceutical market, Sergei Zyryanov, DOCTOR of Medical Sciences, Professor, Chief Freelance Clinical Research Specialist of the Moscow HEALTH Department, explained to RBC.

“Before you give a drug to a patient in real practice, you need to be sure that it is effective and safe,” the expert continued. Therefore, clinical research is a necessity. Otherwise, not a single drug falls into the hands of a doctor or a patient.”

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According to Zyryanov, it is now necessary to conduct three phases of clinical trials before registration in accordance with legal requirements, this process takes years, sometimes more than ten years. “Therefore, research on new drugs should be ongoing and be as convenient as possible for manufacturers. In Moscow, it is precisely thanks to the creation of a single ecosystem for conducting clinical trials that all this is possible and successfully implemented,” he added, noting here the particular importance of import substitution in the current conditions and the development of modern domestic drugs.

How the urban ecosystem works

According to Rakova, an entire ecosystem has been created in Moscow to conduct clinical drug trials. Pharmaceutical companies and drug manufacturers have the opportunity to choose centers for research from about 90 metropolitan hospitals and clinics in 80 therapeutic areas and all phases of research. More than 7,000 qualified professionals with Good Clinical Practice (GCP) certificates and more than 15 years of experience work in these institutions.

Next, the ecosystem contour includes urban laboratories, each of which can become centralized in the case of a multicenter study. There are also local ethics committees, the Moscow City Independent Ethics Committee and a telemedicine center that makes it possible to monitor volunteers remotely.

Technopark of the Moscow Center for Innovative Technologies in Healthcare (Photo: Vladimir Novikov, press service of the mayor and government of the capital / Moskva Agency)

All city medical organizations are connected by a single digital circuit. It ensures the quality and safety of the study, since it gives doctors access to all information about the patient when forming the base of volunteers, and also allows you to see any request for medical help in the city in the process of monitoring him, whether it is a doctor’s house call, an appeal to a specialist in clinic, ambulance or the fact of hospitalization in a hospital.

The work is coordinated by the Moscow Center for Innovative Technologies in Healthcare (“Medtech”), namely the Department for Clinical Research Support established in it. Thanks to the center, companies can quickly access the infrastructure of the city, which simplifies the selection of research centers, volunteers and other organizational issues.

The well-coordinated work of the entire structure allows launching research in the shortest possible time.

The Moscow Center for Innovative Technologies in Healthcare assists in the selection of medical organizations subordinate to the Moscow Department of Health for conducting clinical trials, recommends researchers, and helps with the recruitment of volunteers, Yulia Linkova, Vice President for Clinical Development and Research at Biocad, told RBC. There are a number of other measures that the company plans to apply to Medtech for in the future, she shared.

Biocad has extensive experience in conducting clinical trials based on Moscow centers, Linkova said. Two projects have already been launched on the infrastructure of the urban ecosystem: a study of the innovative drug BCD-180 for the treatment of ankylosing spondylitis (Bekhterev's disease), as well as a study of the drug divozilimab for the treatment of systemic scleroderma.

“Thanks to the interaction with Medtech, the processes associated with the inclusion of participants in clinical trials were carried out as efficiently as possible,” said the Vice President of Biocad. “At the moment, the company is awaiting approval from the federal Ministry of Health to conduct five more clinical trials in such nosologies as neuroblastoma, melanoma (two clinical trials), Devic’s neurooptic myelitis and breast cancer.”

Moscow Center for Innovative Technologies in Healthcare (Photo: press service of the Moscow Social Development Complex)

The initiative itself brings a practical result both for drug developers and medical institutions, and for patients who sometimes find it difficult to find the necessary information about the tests being carried out in the city, Daniil Talyansky, CEO of Generium, is sure. “Thanks to the involvement of the city in this complex process, we see an increase in the quality of ongoing clinical research, an increase in the speed of information dissemination in the medical environment and a higher rate of patient inclusion,” he added. The presence of a coordination center represented by the Moscow Center for Innovative Technologies in Healthcare and the integration of clinical centers, laboratories and research customers into a single digital circuit ensure a high level of results, says Talyansky.

According to the medical DIRECTOR of R-Pharm, Mikhail Samsonov, the initiative is in line with the current tasks of import substitution and ensuring drug safety in Russia. The company historically has a wide network of partner research institutes and conducts research in different countries of the world, but now it has significantly increased the share of clinical trials in Russia. “A key role in their implementation is played by close cooperation with several centers and city clinics in the capital region, including through the Moscow Health Department,” Samsonov emphasized.

So, on the basis of two metropolitan medical institutions - GKB im. Davydovsky and Morozov Children's City Clinical Hospital - and two federal clinical trials of the efficacy and safety of olokizumab in adolescents with juvenile idiopathic arthritis are being conducted, said the medical director of R-Pharm.

How drug research works

The clinical center, which conducts studies of generic drugs, is a separate department where it is possible to place healthy volunteers, the HEAD of the department for organizing and conducting clinical trials of the City Clinical Hospital No. 15 named after O.M. Filatov, Head of the Department of Hospital Therapy named after Academician P.E. Lukom Medical Faculty of the Russian National Research Medical University named after A.I. Pirogov Ivan Gordeev. These are comfortable wards with bathrooms, where volunteers are closely monitored by medical staff, including with the help of CCTV cameras. If some event occurs while taking the drug, it is important to track it up to a minute, the specialist explained. For this reason, all rooms and corridors are equipped with large electronic clocks, operating from a single clock station, which show the same time to the nearest second.

According to Gordeev, entry and exit are carried out using electronic cards. Volunteers during the study cannot leave the department, buy any products in the store, smoke or even drink water in excess of the established norm, everything is very strictly regulated by the protocol.

Studies are conducted both on patients and on volunteers, we are talking about completely different nosologies. Most of them are of a cardiological and therapeutic direction, and trials are also underway in vascular surgery, cardiac surgery, neurology, ophthalmology, obstetrics and gynecology. All studies are carried out exclusively with the consent of patients and volunteers.

Currently, in the City Clinical Hospital No. 15 named after O.M. Filatov conduct bioequivalence studies of two domestic antiviral drugs in healthy volunteers and drugs for the treatment of rheumatoid arthritis. In addition, there are a number of cardiac studies that began even before the CORONAVIRUS pandemic. This is a long process, when patients come every six months, receive the drug, undergo medical examinations and examinations.

During the study, it is controlled that the drug is taken in accordance with the planned schedule, Gordeev explained. All adverse events are monitored; everything is recorded so that the company can then collect and study statistics based on this data. By the way, the instructions enclosed in the packaging of each drug are largely based on those adverse events that were noted by doctors in clinical trials, he said.

“We also conduct so-called observational studies, when large groups of patients are analyzed in real clinical practice on the basis of fairly simple questionnaires, tables or electronic systems accessible to many doctors. With their help, it is possible to identify the incidence of complications, to evaluate the effectiveness of a particular drug in a very large population,” Gordeev shared. — The Moscow Center for Innovative Technologies in Healthcare helps us with the selection of volunteers for research. He acts as a link for all participants in the process and provides really great support. The center helps us build communication with pharmaceutical companies, conducts educational events for doctors with the involvement of leading experts in the field,

Laboratory on the basis of the State Clinical Hospital named after S.P. Botkin (Photo: press service of the Moscow Social Development Complex)

When in July 2020 the task was set to organize a research center for the study of the Sputnik V vaccine, the team of researchers was formed from their own doctors, nurses, administrators, Natalya Shindryayeva, chief physician of the Moscow polyclinic No. 2, told RBC . All of them had to be trained for the GCP (Good Clinical Practice) certificate, which any research doctor must have, she recalled.

According to Shindryayeva, a single coordinating center for this study developed a standard for conducting clinical trials, which included training the entire team, the schedule of the functionality of each participant, creating infrastructure, navigation, preparing the premises where the screening was carried out and the vaccine was administered, forming the routing of study participants, monitoring the implementation of all stages of observation of volunteers, deviations and much more.

“Clinical trials of the Sputnik V vaccine have become the largest coronavirus vaccine trial in the world,” Shindryayeva said. “22 research centers were involved in it and more than 33 thousand volunteers took part,” the head physician recalled.

Prior to this, the clinic had already undergone clinical trials and was accredited for all their types and phases. But a study of this magnitude, in which it was necessary to recruit many volunteers in a short time, screen them, administer the vaccine in two stages, constantly observe, according to her, took place for the first time.

The research center at Polyclinic No. 2 was one of the first to receive the vaccine for research, she stressed.

Since 2020, productive cooperation has developed with the research centers of the Moscow Department of Health, and most importantly, a single coordination center has played a large role in this interaction, the National Research Center for Epidemiology and Microbiology named after N.F. Gamaleya, whose specialists developed Sputnik V.

“The result of this cooperation was the successful conduct of an unprecedented study with the participation of more than 33 thousand volunteers and the inclusion of more than 20 medical institutions in the city of Moscow,” representatives of the center emphasized in a conversation with RBC. “Currently, the cooperation continues successfully.”

Advice and money

The metropolitan ecosystem of clinical trials provides domestic pharmaceutical companies with both organizational and financial support.

Organizational support implies an assessment of the feasibility of the clinical trial itself, the selection of city medical organizations with the necessary equipment for the study. Research team and volunteers are selected. The city also organizes interaction with ethical committees and legal support.

CT scan in the city polyclinic No. 6 (Photo: press service of the Moscow Social Development Complex)

Moscow has created a platform for communication and solving the most pressing issues of conducting clinical trials, Zyryanov from the Moscow Department of Health noted in a conversation with RBC. Organizational support includes the search for clinical centers, and the solution of legal issues, and the provision of equipment, and much more. A pharmaceutical company can contact Medtech for any questions and they will help, he assured.

In addition, staff training can be attributed to organizational support: the study simply will not take place if there is no trained doctor or nurse who knows how to conduct clinical trials and maintain documentation, Zyryanov emphasized. According to him, more than 500 people were trained last year, and almost 600 specialists are planned to be trained this year. In addition, monthly webinars are held on the most significant issues of clinical research - the Moscow Researcher School.

“The city is actively involved in the search for centers and expert doctors, building a system for informing patients and volunteers,” says Talyansky from Generium. “Now and in the future, this support is essential, because it allows Russian patients to access modern therapy faster.” As an example of successful cooperation, he cited trials of a nasal vaccine for the prevention of coronavirus. “Now we are working together on a protocol for psoriasis and are planning to start a whole series of studies in the near future,” Talyansky shared his plans.

According to Biocad's Linkova, the ecosystem has already shown its effectiveness on two projects of the company: in the BCD-180 study, the recruitment of participants in the second phase, which is now underway, has been completed. Divozilimab is currently being recruited for a phase 3 trial for the treatment of systemic scleroderma. “We plan to continue to cooperate with Medtech in all of our multicenter clinical trials, as well as to use other measures to support clinical trials,” the vice president of the company concluded.

The capital program allows pharmaceutical companies to receive financial support, namely, to compensate for part of the cost of conducting a clinical trial. According to the rules, the amount of compensation cannot exceed half of the total cost of conducting a study in a city medical organization.

Moscow Center for Innovative Technologies in Healthcare (Photo: press service of the Moscow Social Development Complex)

“Moscow is ready to financially support clinical trials on the most significant and important drugs that can be applied in the metropolitan healthcare system, will help achieve indicators of increasing life expectancy, reducing morbidity, and so on,” Zyryanov emphasized. “The decision on support is made at a meeting of the clinical committee at the Department of Health, and the main freelance specialists of the department take part in the discussion of the issue.”

According to him, in the short time the project has existed, two clinical trials have already received this support, and the relevant agreements have been concluded.

“So, the Moscow government allocated 6 million rubles. to support the research of a drug aimed at the treatment of chronic idiopathic thrombocytopenic purpura, an autoimmune hematological disease associated with increased destruction of blood elements - platelets involved in its coagulation processes, ”said Rakova. She added that the study drug is a modern biosimilar to a foreign one and is intended for the treatment of patients with a severe course of the disease, in which disability can occur in the absence of therapy.

“If drug developers were so supported by everyone, then we would already be ahead of the rest. We wouldn’t need import substitution, we ourselves would become suppliers of fundamentally new, most innovative drugs,” the director of the N.F. Gamalei Alexander Gintsburg. — Our institute has always seen support from the government of Moscow, the capital's depzdrav, and not only saw it, but also felt it. Both organizational and financial.

Ecosystem efficiency and perspectives

The completed study of the vaccine, which was developed by the N.F. Gamaleya is a clear confirmation of the efficient operation of the ecosystem, Zyryanov believes.

“If there was no such ecosystem, then it would be impossible to organize such a study in two to three months and recruit more than 33 thousand volunteers,” he said. “It is thanks to the well-coordinated and confident work of our teams, the Unified Coordination Center, the centralized laboratory, the telemedicine center, as well as the presence of a unified medical information system integrated into the process of conducting clinical trials, that we were able to conduct a high-level study of the Sputnik V vaccine and prove its effectiveness and safety.

Telemedicine Center (Photo: press service of the Moscow Social Development Complex)

As part of the study to create the Sputnik V vaccine, Moscow screened more than 113,000 people in just 3.5 months and included more than 33,000 volunteers in the study. The study was conducted on the basis of 22 medical organizations and was completely digital: all medical documentation was conducted without the use of paper, exclusively in electronic form in EMIAS.

Over the entire period of the clinical study, the Centralized Laboratory, created on the basis of the Diagnostic Center for Laboratory Research of the Moscow Department of Health, conducted about 820 thousand studies. They were performed within a day from the moment of biomaterial sampling. Thanks to the well-organized logistics, the biomaterial arrived at the laboratory within four hours. The results of the team's research were seen online electronically.

“Only thanks to a very clear modern organization, namely, that in Moscow absolutely all stages of medical care are digitized and computerized, it was possible to effectively conduct a study in such huge volumes in such a short time,” Gunzburg emphasized. According to him, now the center's scientists are focusing on clinical trials at the capital's base of fluorothiazinon, a drug for the treatment of bacterial infections. There are also plans to conduct clinical trials of a fundamentally new vaccine against tuberculosis, aimed not only at treatment, but at prevention, protection against infection.