FDA inspections produce solid evidence of high quality clinical trial data originating in Central and Eastern Europe

FDA InspectionsClinical Accelerator is a clinical CRO with a special focus on Central and Eastern Europe currently operating in 11 countries of the region: Belarus, Estonia, Georgia, Hungary, Latvia, Lithuania, Moldova, Poland, Romania, Russian Federation and Ukraine (listed alphabetically).

 The quality of clinical trial data originating in our countries of operation and its acceptance by FDA is a frequent topic in our discussions with Clinical Accelerator’s partners and clients. In this newsletter we present an analysis of the latest data made available by FDA.

We know first-hand that the clinical trials we conduct in Central and Eastern European countries produce data meeting all the standards set by regulatory agencies around the world. However, we’re also aware of the misconception that clinical research carried out in this region does not conform to the standards of data quality and Good Clinical Practice seen in Western Europe and Northern America.

How do countries in Central and Eastern Europe compare with the rest of the world?

Today, clinical trials operate on a global stage. According to the 2010 report of Office of Inspector General, US Department of Health and Human Services, more than 80% of the US FDA approved marketing applications now contain data acquired outside the US. It is unsurprising then, that the FDA is increasingly interested in foreign sites involved in conducting clinical trials.

Clinical trials sites

Central and Eastern Europe (CEE) is a major contributor of investigative sites to global clinical trials, currently providing 11% of all sites worldwide. The region is especially attractive to sponsors thanks to the excellent levels of patient recruitment that are characteristic of CEE countries. The average reported recruitment rate in CEE is of 10.3 patients per site compared to 7.5 per site in Western Europe.

In Central and Eastern Europe, Russia is currently ranked No. 1 country by the number of sites participating in industry-sponsored clinical trials (4696) followed by Poland (4320), Czech Republic (2201), Hungary (2115), Ukraine (2002), Romania (1618) and Bulgaria (1004). The number of sites participating in clinical trials in the Baltic countries stands at 386 for Lithuania, 320 for Estonia and 319 for Latvia.

By the number of sites participating in FDA-overseen clinical trials, Russia is currently ranked No. 2 in Europe (after Germany) and No. 4 in the world (after US, Canada and Germany) with 3340 sites. The Ukraine is also climbing up the list fast, currently being No. 11 in Europe and No. 19 in the world with 1141 sites. For comparison, there are 2831 sites overseen by FDA in the UK and 1866 sites in India.

FDA inspections

It’s unsurprising that facilities operating in CEE, and particularly those in Russia, have attracted scrutiny from the FDA, given the high number of clinical trials being operated in the region. To date, 278 FDA inspections have been carried out in CEE. The majority of inspections have been conducted in Russia (100) and Poland (91). Discounting the USA, this gives them a worldwide ranking of 4th and 5th, after Canada (194), the UK (119) and Germany (110). Other contributors to the number of FDA inspections in CEE are Hungary (25), Czech Republic (17), and Ukraine (26), with Romania (15), Latvia (9), Lithuania (2), Estonia (6) and Georgia (4).

A more focused analysis of the published FDA data reveals that in the last decade 87 inspections have been carried out in Russia and 82 in Poland, pushing them up the rankings to number 1 and 2, followed by Canada (79), Germany (79) and the UK (38). This reflects Russia and Poland’s growing status as leading global locations to conduct clinical trials.

FDA inspection outcomes

The results of these inspections have proved to be somewhat unexpected for some critics of the so-called “emerging locations” in CEE.

Based on the most recent statistics available, our own analysis of FDA inspections outcomes based on the top 5 most inspected countries shows that Russia and Poland outperform Canada, Germany, and the UK. In the last decade, the percentage of NAI inspections (no objectionable conditions or practices were found during the inspection) was higher in Russia (66.3%) and Poland (58.5%), compared with Canada (54.4%), Germany (47.8%), and the UK (42.1%). For inspections where action was indicated, the average number of deficiency codes in Russia (1.24) and Poland (1.44) was lower than in Canada (1.67), the UK (1.95) and Germany (1.89).

Our own analysis is supported by previously published studies. A 2010 analysis of FDA data showed that Eastern Europe (with 264 US FDA inspections) has the best overall results worldwide, with only 3.3% of its site inspections having three or more deficiencies, 0.85% in Russia and 0% in the Ukraine, compared with 20.2% in Western Europe after 506 inspections.

A more recent analysis comparing CEE with Western Europe and the USA gives an equally positive account. Clinical trials in CEE are more likely to result in NAI (No Action Indicated) outcomes of FDA inspections: CEE (39%), Western Europe (16.6%) and USA (21.5%). The average number of deficiencies per inspection is lower in CEE than in Western Europe and the USA, at 0.99, 1.99, and 1.59, respectively. Finally, the rate of inspections for which objectionable conditions were found, warranting regulatory and/or administrative sanctions, were lower in CEE (1%), than in the USA (2%) and Western Europe (4.5%).

Repeated analysis of FDA inspection data has shown what we’ve always believed at Clinical Accelerator – that clinical trials conducted in CEE are of an equally high standard to those carried out in Western Europe and Northern America. We believe that all the extensive evidence of the quality of clinical trial data originated in CEE, Russia & Ukraine acquired as a result of FDA inspections over the last 5 years should be very reassuring for international companies considering placing their clinical trials in these regions.

Although the FDA has conducted fewer inspections in CEE countries neighboring Russia and Poland, the healthcare systems are similar across the regions, so it’s likely that these countries will replicate the good results seen in Russia and Poland. Due to the fast growing contribution of these countries to global clinical trials and increasing interest of FDA, we expect more evidence of the quality of clinical trial data will emerge.

We will continue to monitor the data coming from FDA inspections and will re-visit this topic again in one of our future newsletters.

Sources:

Challenges to FDA’s Ability to Monitor and Inspect Foreign Clinical Trials.Department of Health and Human Services, Office of Inspector General (Report # OEI-01-08-00510), 2010. Available online at http://oig.hhs.gov/oei/reports/oei-01-08-00510.pdf

US Trial Registry.Available on line at http://www.ClinicalTrials.gov

Karlberg JPE. US FDA Inspection Findings, Fail to Justify Globalization Concerns. Clinical Trial Magnifier 2009;4:194-212. Available online at http://www.ClinicalTrialMagnifier.org .

Karlberg JPE. Clinical Trials Overseen by US FDA. Clinical Trial Magnifier 2010;3:279-297. Available online at http://www.ClinicalTrialMagnifier.org

Caldron, P. H., et al. (2012). “Why (not) go east? Comparison of findings from FDA Investigational New Drug study site inspections performed in Central and Eastern Europe with results from the USA, Western Europe, and other parts of the world.” Drug Des Devel Ther 6: 53-60.

This entry was posted in Central and Eastern Europe, Clinical Accelerator, FDA, Regulations. Bookmark the permalink.

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