By Tomas Novak (Czech Republic), Maxim Belotserkovsky (Germany), Veronika Fekete (Hungary), and Katarzyna Moscicka (Poland) 

 

September 12, 2013 | Following the fall of the Iron Curtain toward the end of the 1980´s, the region of Central and Eastern Europe (CEE) including post-Soviet states (altogether more than 20 countries) was exposed to a growing demand among the pharmaceutical companies eager to conduct clinical trials. The CEE region has a population of 340 millions, comparable with the United States or Western Europe. The countries adopted ICH-GCP standards during the ‘90s along with the US and Western Europe. Twelve CEE countries have joined EU: Poland, Czech Republic, Hungary, Bulgaria, Slovakia, Romania, Latvia, Lithuania, Estonia, Slovenia, and Croatia (July 2013). The new EU member states have integrated their legislation into the European legal framework, including the portions covering clinical trials. 

 

We have learned that this region—particularly the countries in the West of the region: Poland, Czech Republic, Hungary, Estonia, Slovakia and Slovenia—offers trial sponsors treatment standards and diagnostics technologies very close to the quality of Western European countries. 

 

Gradually CEE countries have become a traditional place for clinical trials. There are a number of reasons behind the growing demand for these countries. Most countries inherited centralized healthcare systems. Historically, most have a limited number of specialized medical centers that enable substantial concentrations of patients. The physicians and nurses in CEE countries are well-educated. Both community-owned and private clinics in these countries are able to easily enroll not only pretreated but also treatment-naïve subjects, while Western Europe in many cases provides the same “recycled” pool of patients who often are already rather treatment resistant. The existing vertical referral system in these countries provides only minimal competition (if any) for patients among medical centers. Available access to life-long medical records of patients enables lower rates of screening failures and premature withdrawals. Though the region has a growing population migration rate, it is still much lower than Western Europe, which enables better long-term follow-up. 

 

Interestingly, average site productivity in the region is often twice as high as Western Europe or the US, and clinical research professionals are often either physicians or pharmacists, or hold scientific degrees, which enables better and more efficient understanding of the study assumptions and methodology, though it is important to remember that study documents should be translated into local languages.

 

Infrastructure and Oversight 

 

The region’s infrastructure is also a selling point. Most of these countries already own up-to-date diagnostic and treatment facilities, including fusion imaging machines, genetic diagnostics and modern electronic data collection means. Usually CEE countries deal with phase II and III clinical trials, in which the region provides a large pool of patients, but the number of successful Phase I trials in multiple indications is growing as well. The most represented areas of clinical trials are oncology, cardiology, rheumatology, hypertension and neurology. 

 

In general, more than half of the regulatory inspections in these countries did not require any follow-up action. All the inspections carried out in this region raised fewer issues of compliance in terms of protocol adherence and data storage than inspections at US and Western European sites. Also, fewer problems have been observed regarding Informed Consent Forms and study procedures, inadequate drug accountability and failure to report adverse drug reactions compared to issues observed during inspections in Western Europe and the US. This region also displays the lowest rate of inspections that require official or voluntary action. 

 

The number of IND clinical trials registered in individual countries according to clinicaltrials.gov shows a rise of the absolute number of clinical trials in the region of CEE between 2005 and 2011. The trend is stable over the last six years and constitutes an average growth of 31%. Nevertheless in comparison with the other “emerging” regions (e.g. Latin America and Asia Pacific), the growth is not that high. During the same period of time, the share of clinical trials in the US and Western Europe is practically stable, probably indicating “saturation” of these clinical trial markets. The distribution of clinical trials of different phases in CEE is also fairly stable. The most growth has occurred in the number of phase I studies (from 19 newly registered in CEE phase I studies in 2005 to 79 in 2011). The steepest increase in the number of Phase I CT in CEE region is seen primarily in the Czech Republic (from 1 to 10), Poland (from 5 to 13), Hungary (from 2 to 14 ), Bulgaria (from 0 to 9) and Russia (from 6 to 12). Our experience in performing more than 30 Phase I trials in CEE region also indicates high quality of the data and the growing interest of the sponsors to perform Phase I trials here.

 

Study Startup 

 

Comprehensive legislation on clinical trials is available in all CEE countries. The regulatory processes and submission guidelines vary from country to country and should be dealt with individually for each trial on the local level, but generally follow internationally-accepted practices and GCP rules. Some variation in the procedures of regulatory and ethics review itself does not pose a problem given the availability of local experts in charge of the start-up phase.

 

Based on our own experience of more than 300 clinical trials in the region, the system to obtain study authorization works well. At the same time, delays may happen due to requests for additional documentation placed by authorities. The approval process in CEE region—particularly the countries in the West of the CEE region—takes an average of 3 to 4 months. The process can take 5-6 months in Croatia and Serbia, while Russia and Ukraine are usually somewhere in between. Georgia stands out in terms of speed.  

 

The CEE region is one of the optimal options due to rapid enrollment, high quality of data, motivation and loyalty of investigators, low dropout rate, reasonable costs, and educated clinical research professionals. These countries can enable treatment and data quality while cutting clinical trial expenses.