Russia has a long and well established background in clinical research supported by various audits including ones made by the FDA and other state agencies, world sponsors, etc. The country also has a strong track record in recruiting patients with a high commitment of site staff.
The goal of this article is to reveal to those yet to venture into Russia of the country’s potential as a hub for clinical research in Eastern Europe.
Clinical Trials in Russia
To place things in perspective, Russia is one of the biggest countries in the world with a population of 145 million inhabitants (sixth place in world). As an emerging economy, Russia is in sixth place in terms of GDP (per PPP).
While political issues enveloping the country could deter international sponsors intending to enter Russia, the government has made extensive efforts to protect any foreign businesses working in the country.
Meanwhile, the Russian medical system is largely centralized, with most hospitals ruled either by the state, by regions or by cities. This is an important consideration sponsor companies should factor when making study agreements with hospitals or principal investigators.
The number of clinical trials approved by health authorities (HAs) has remained quite stable for years. The table below demonstrates the number of only international multicenter clinical trials approved between 2004 – 2015.
Source: Association of clinical trials organization (http://acto-russia.org/en/)
At the same time, there’s been a substantial growth in the number of trials sponsored by local pharma companies: bioequivalence in level 60-80 trials in 2004–2011 has soared up to 140–210 after 2012. On the other hand, bioequivalence trials sponsored by foreign sponsors have increased to approximately 150-200 every year after 2012. There are many reasons for that growth, chief among them is the major change in Russian regulations that has required local patients to register for trials.
Russian trial centers have passed through many audits being measured by FDA standards. The overall reputation is very good as the number of findings tends to be very low. This is especially important as the recruitment rate of Russian sites is usually better on average than in countries across Europe and North America.
Modern technologies, like Electronic Data Capture (EDC), are equally available due to the modern communication infrastructure that is available for a majority of hospitals.
Plenty of companies are working in the Russian market; together with world leaders there are many mid-size and small companies. While larger companies have sophisticated software and internal procedures with GCP trained staff, there are plenty of smaller ones, which, despite working on a restricted budget (not having special software) have experienced and well trained staff that’s able to provide a high-quality service for international businesses.
It’s also worth mentioning there are single organizations working at a sub-standard level, meaning a thorough audit before starting with a new company is very important.
Major Considerations on setting up Clinical Trials in Russia
The first question that must be answered by every clinical trial sponsor before coming to Russia is: ‘What are you hoping to gain by initiating a trial in Russia?’ It’s important to identify two major strategies: obtaining registration for a product that is already in market in other countries or recruiting patients for international clinical trials.
Regulatory approaches would be different (despite the list of documents for submission is similar) and describing the difference falls outside the scope of this article.
Any company that plans to conduct clinical trials in Russia should have robust support from a locally based regulatory team that has a deep understanding of the requirements and is aware of any regulatory changes. Red tape is still an important factor of life and business; the list of requested documents (translated in Russian, powered by apostil) is quite long, so it’s important companies make sufficient time to prepare while planning the trial.
The regulatory timeframe, from submission to approval is approximately two to four months and that may vary from case to case. Despite the continuous improvement of Health Authorities, the observation of timelines is still an issue and applicants should always keep an eye on it.
The process of submitting documents for clinical trial approval consists of two major steps: knowledge of the documents and science expertise.
There are usually a lot of fears around questions addressed by MoH during document review, such as having the requisite experience. For the most part, these questions are of a technical nature and can be fixed easily by providing either a specific explanation or additional documents.
Scientific expertise is more straightforward in scientific background. Questions can range from having sufficient preclinical data until justification of statistical design. Nevertheless, a thorough explanation is usually enough to satisfy HA experts.
Additionally, more attention needs to be paid to trials involving children or to those in vulnerable populations. Sponsor companies must have a robust justification for why they intend to carry out a pediatric clinical trial. They must be able to demonstrate sufficient data from adults as such trials are usually approved as a result. It is as well determined by specific regulations.
Expertise of trials in other vulnerable populations is mostly of ethical interest. Things like how to obtain informed consent while, for instance, a patient is in a coma must be described very precisely. Before proceeding with such protocols we recommend you get feedback from investigators.
Central ethics falls within regulatory approval and is actually part of MoH. I recommend having local ethics approval as well.
What’s more, health insurance for patients is another key consideration sponsors must factor. Health insurance is regulated by law, with fees determined on a case by case basis and typically don’t present an issue for sponsors. However, the only one “peculiarity” to consider is that federal law doesn’t use the term “phase” for clinical trials but uses the term “goal” of clinical trials that are precisely described in regulation.
Site Selection and Investigators’ Fee
Site selection is always a crucial factor on successful setup of a trial to guarantee that the estimated number of patients is recruited in due time. The case report form submitted either by paper or electronically, must be completed in time having protocol deviation at a reasonably low level. Most companies have their own databases and know each good PI personally.
Site staff is highly motivated in clinical trials due to few obvious reasons: payment and be supported by recognizable companies in their science activities. GCP is a well known standard and is in normal requirement for submission of sites for clinical trials.
There are quite a lot of sites that can provide patients while they are naïve about the requirements and in even GCP. They need special attention and I wouldn’t recommend cancelling their involvement from beginning; it’s essential you at least meet the PI and site staff before the trial begins. I know exemplars when naïve site provided excellent quality data and very experienced site provided troubles.
The most common mistake of sponsor is judging about trial center based on formal documents. The possibility of recruiting patients is perhaps mistake number one; often (not always!) sites overstate number of available patients. I recommend that you analyze such data against other sites and any statistics available in the public domain. Simply put: the best source of information about how site is good is your own experience.
The next important question is the identification of a fair fee per patient. I’ve heard the myth that conducting trials in Russia is generally cheaper,but that is a common misconception. The cost is generally the same and the exchange rate of local currency has dropped twice within last two years, which doesn’t change the situation as most of the sponsors estimate fees in Euros or US dollars. My advice to readers would be to plan trials in Russia as though the expense would be the same as though you were conducting a study in western Europe or in the US.
Large travelling distances is another issue worth mentioning as that can have a direct influence on logistics costs whether it is couriers or CRAs’ travel time.
As for CRAs, there are different solutions (we all have heard the terms “regionalization”, “remote/distant monitoring”, RBQSV); of course any and all of them have a right to exist and companies are using them with this or that success. When planning the trial, it is always worth remembering that obtaining solid data is dependent on your own experience.
The advanced approaches to monitoring (distant, risk-based) should be used with reasonable precaution (though as it is in any other country) as the personal contact to PI and/or hospital staff is yet very important to secure timely and high quality data collection.
*Valery Novikov is the General Director Deputy in Clinical Research at Generium