Russian research expert discusses training
Russian sites have high enrollment
[Editor’s note: In this Q&A interview, Anatoly Gorkoun, MD, PhD, project manager of clinical operations of PSI Pharma Support International in Saint Petersburg, Russia, discusses some of the differences and similarities of clinical trial research in Russia and how U.S. investigators might prepare to collaborate on these projects. In this issue, Gorkoun discusses investigator training and best practices. In a follow-up story that will appear in the April issue of Clinical Trials Administrator, Gorkoun discusses trial audits, monitoring international sites, and regulatory considerations.]
CTA: How has clinical research expanded in Russia, and why has the country attracted more interest from the United States in recent years?
Gorkoun: First of all, a piece of general knowledge: Russia has its population up to 150 million inhabitants, and it has an 11-time-zone territory. I need to admit that our company has got a unique geographic experience, involving sites in all the biggest cities from the West to the East. Thus, there are clinical trial sites in the city of Kaliningrad, which is on the Baltic Sea, the most Western Russian point on the map, and in Sakhalin, one of the remotest Far Eastern locations, bordering with Japan.
In the recent years more and more clinical sites are getting involved in clinical research. There are two main reasons for such intensive expansion:
1. Russian sites provide high enrollment. The phrase, "Go where the patients are," explains one of the reasons the country attracts more interest. I would say that most of Russian sites never experience problems with enrollment, and it’s applicable to most of the investigated diseases/pathologic conditions.
2. Russian sites produce data of a high quality, which was confirmed by numerous sponsors’ and Food and Drug Administration audits.
Despite this overwhelming involvement of sites all over the country, there still is a huge potential that can be used if the expansion process continues. The local sites have advanced facilities, sophisticated modern equipment, and very experienced medical staff. Maybe some of the investigators don’t have an extensive clinical research experience, but proper training can easily improve the situation.
CTA: What are the chief training objectives/considerations for investigators working on or with clinical research sites overseas and, specifically, in Russia?
Gorkoun: The main training objectives applicable for Russian investigators, are the same as for American or Western European investigators. Of course, there might be different training requirements for some other countries. For instance, those which don’t have an extensive, many-year experience in clinical research, might need basic training in safety reporting or source documentation maintenance, but it’s not applicable for our case. Most Russian investigators have extensive hands-on experience in clinical research, and in most cases only study-specific training is needed.
Previous investigators’ clinical research experience is evaluated during site selection visits and thus, we identify needs for training if a particular site is selected for the study conduct. From our long-term experience, in most cases there are study-specific training issues such as study protocol, investigational product, study-specific procedures, study-specific requirements for safety reporting, etc.
If some of the investigators need to have their general clinical research knowledge refreshed, let’s say in good clinical practice [GCP], they will be provided with this additional training.
And only in those rare cases when a clinical research-naïve site is going to be involved into the study conduct, the site will be provided with all basic training prior to the study’s start. It can be the case when some site with insufficient research experience has a broad clinical expertise, access to a wide target population, and sophisticated equipment. If additional sites are needed to be open , this site can be considered as a candidate and, after the successful respective training, can be approved to run the study.
Speaking about training goals, I would like to highlight that it’s important not only to provide the investigators with the respective information, but also it’s very important to make sure the information is understood in the right way.
CTA: Would you please describe a best practice model for general training for investigators?
Gorkoun: 1. At site selection/evaluation visits, investigators’ level of expertise is clarified.
2. Training is provided at an investigators meeting. Who attends the investigators meeting? The principal investigator and one of the sub-investigators, who are MDs. In addition, there are the site data manager/research coordinator, who is an RN, or a required specialist, such as a lab specialist or radiologist, etc. Normally, two or three people from each site attend the investigators meeting.
Since the investigators meeting is assigned for a large audience, it’s possible to train all participating sites simultaneously. From our experience, training at the investigators meeting is very important for future compliance and quality of data. And we pay special attention to the investigators’ meetings preparation. The investigators’ meeting cannot be considered as only a social event with the main purpose "to socialize."
3. Training prior site initiation visits may be provided, if needed. Especially, it’s applicable to the sites less experienced in clinical research. Usually it’s for one-day, on-site training right before the site initiation visit. It can be general clinical research training in GCP, as well as study-specific training.
4. Training at site initiation visit. If during the site initiation visit the monitor identified a lack of study-specific or general knowledge, additional training is provided at this visit, and it’s documented on the site initiation visit report. So it can be considered as on-site, additional re-training/ training in study procedures/protocol, if needed.
5. Ongoing training or re-training in the course of the study are done at routine monitoring visits or by the phone. This is provided by monitors, and in Russia, most monitors are MDs.
The general training means GCP and/or any other clinical research-related experience that can be useful for any clinical trial. It’s not study-specific. They can be the principles of ICH GCP, ethics issues, investigator’s responsibilities, study documents, etc.
In Russia there are several GCP courses the investigators can attend, where MDs and medical/registered nurses can get the necessary basic knowledge. After the investigators successfully pass the respective tests, they obtain GCP certificates. But it’s not mandatory to attend the courses.
The other places where the investigators can get general knowledge are congresses and conferences, both national and international, where they can listen to the respective clinical research-related presentations. Also, clinical research workshops, organized by Pharma companies or clinical research organizations (CROs) are useful. It might be GCP workshops, or some specialized workshops, like "informed consent process in pediatrics," for instance. These workshops are very valuable since they are concentrated on narrow issues.
And finally, the investigator meetings are a place for training. They are dedicated to discussing study-specific issues. Normally, at each investigator meeting at least one presentation is dedicated to discussing the most critical GCP questions, such as the informed consent process, the investigator’s responsibilities, study documents, etc.
The trainers are CRO or sponsor’s project managers, senior clinical research associates, experienced clinical research associates, safety officers, data managers, and others.
We think that investigators have been provided with proper training if we can see throughout the study these objectives:
- proper maintenance of source documents;
- GCP, regulatory, protocol, and procedure compliance;
- adherence to ethics standards;
- absence of violations or misconduct;
- reasonable number of explainable deviations, low rate of data clarifications.
CTA: What are some of the major challenges with delivering training uniformity in global trials?
Gorkoun: The main challenges are the following: different languages, different cultures and social conditions, sites’ locations in different countries and continents. One of the challenges is diversity of the languages the investigators speak. It’s obvious that the study documents, issued mainly in English, which is the industry’s language, must be understood in the right way by each investigator at each site and in each country. Incorrect treatment of the study protocol or procedures can lead to irrecoverable consequences. So, before the site is initiated, we need to make sure that the investigator got everything correctly.
Speaking about site location, in Russia sites are scattered from West to the East within an 11-time- zone territory. It’s a long way from one part of the country to another. The flight from St. Petersburg, Russia, to one of the Far Eastern sites takes about eight or nine hours. Of course, it’s a challenge to manage face-to-face training, and it’s even not very easy to handle training by the phone, taking into account the seven-hour or more time difference.