Investigator-Led Trials On The Rise in Russia
Executive Summary
The number of investigator-led trials is rising in Russia as scientific knowledge grows and doctors work more closely together. But the methodological framework is still patchy and companies planning to get involved in such trials need to know the possible pitfalls and be prepared to support investigators in their work.
Several factors are behind the recent growth in popularity of investigator-initiated clinical trials in the Russian Federation. According to Maria Nassonova, executive manager at the Russian CRO Almedis, these include the limitations of trial programs led by pharmaceutical companies, the growing range of therapeutic targets, and increasing collaboration among doctors facilitated by modern communication channels and data management tools.
Sometimes, though, says Nassonova, Russian investigators running such trials do not have sufficient knowledge of the requirements and processes involved in starting and conducting investigator-initiated trials (ITTs). They may also not have enough experience or tools at their disposal to manage the trial budget efficiently.
Companies considering whether to work with investigator-led trials in Russia should therefore consider ahead of time what kind of support the investigator will need to carry out the trial, Nassonova writes in the latest newsletter of the Russian CRO association ACTO.
IITs are becoming more popular in Russia for a number of reasons, she says. For example, trial programs run by pharmaceutical companies “do not provide complete information about features of medicines for the benefit of a wide pool of potential patients,” as they are “first and foremost” aimed at supporting regulatory approval for medicines and rolling them out onto the market.
Protocols for trials sponsored by the pharmaceutical industry “have design flaws which make it impossible to evaluate the effectiveness of the medicines under real-world conditions,” while clinical development programs are “focused on the most commercially appealing market segments/therapeutic areas.”
Another reason for the growing popularity of such trials is qualitative growth in knowledge about the pathogenesis of various diseases, improved classification of diseases (for example classification of tumors by mutation type), and the identification of a large number of potential new targets for intervention with medicinal products, Nassonova writes.
Furthermore, a greater degree of cooperation and awareness among doctors has been made possible by contemporary channels of communication (internet, social media and IT), which “facilitate collaborative work between geographically remote participants.” The introduction of efficient tools for collecting and managing data is also playing a role.
The Russian Federation has a legal basis for conducting investigator-initiated clinical trials, under Article 38 of the 2010 Federal Law No 61-FZ "On Circulation of Medicines," which says that research organisations and vocational education institutions can conduct clinical trials. However, no statutory provisions specifically regarding IITs have been worked out in detail: all regulations affecting IITs have been extrapolated from those that apply to clinical trials in general.
Challenges
Nassonova says that pharmaceutical companies generally consider IITs as “a significant aid in the life-cycle of their medicines in an environment of fierce competition” and increased expenditure on drug development, as well as “a cost-effective means of seeking out new indications and niche applications.”
But Russia poses some difficulties for IITs – similar to those seen in other, often more developed markets – that stem from “the significant increase in responsibility falling on sponsor-investigators when conducting IITs as opposed to IMCTs or research,” Nossanova observes. “These responsibilities include processes which investigators may be either completely unfamiliar with, or else only very superficially aware of.”
For example, the potential sponsor-investigator is expected to prepare a synopsis or protocol for the trial. If they are applying to a pharmaceutical company for a grant, then the company must review and approve the protocol. This means that the design, aim and objectives of the trial, and the justification of the choice of variables and methods of evaluation, as well as the calculation of the sample size, must be correctly described in the trial protocol in line with current understanding at the global level.
“Unfortunately, a situation is often encountered whereby a potential sponsor-investigator is not in a position either to distinguish between an observational project and an interventional clinical trial, or to align planned aims with realistic capabilities, including the necessary sample size,” Nossanova notes.
Also, she says, it is often the case that doctors do not have an adequate understanding of the current requirements governing the collection and management of clinical trial data, the systems used for this purpose, or the coding of medical terms.
In conclusion, the Almedis executive manager says, it is clear that the significance and number of investigator initiated trials is on the increase in Russia, but companies wanting to get involved in such initiatives should remember that the methodological framework for conducting IITs does not always meet current requirements. “This must be accounted for when projects of this type come under consideration, and plans should be made in advance to determine the kind of support investigators require in order to realise their research concepts.”