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Central and Eastern Europe:
A Hot Bed for Drug Development
Clinical research activity in Central and Eastern Europe (CEE) is surging. Large populations, a
profusion of motivated participants, qualified investigators, recognized data quality, accessible
trial sites and reasonable costs are beckoning sponsors to the emerging market.
Despite the boom, the region has plenty of room to grow. Large nations, such as Russia and
Ukraine, have ample capacity to support more sites and clinical research in many of the smaller
states is in its infancy. Some analysts estimate only 15% of the region’s clinical study enrollment
potential has been tapped.
While the opportunities are considerable, inexperience in CEE can result in denied applications
and costly delays. Given the considerable regulatory, legal, and cultural variances in the region,
strategic partners with strong site relationships, therapeutic expertise and a specialized knowledge
of the region are critical to success.
A large, untapped population
Collectively, CEE countries boast a population of 392 million, well over half of whom live in Russia,
Ukraine or Poland.
Attracted by those numbers, trial activity in CEE has soared in recent years. Currently almost
15,000 registered trials -- just over 10% of the worldwide total – are taking place in 26 CEE
countries, according to ClinicalTrials.gov. Of those, more than half are taking place in Poland,
Russia and the Czech Republic. Indeed, the Czech Republic, with a population of just over 10
million, has nearly as many registered trials as India, while Poland’s total approaches that of Brazil.
Despite the steady increase in studies, trial activity in CEE relative to the
overall population remains low compared to Western Europe. For example,
while Ukraine’s population is roughly half that of Germany’s (45.7 million vs.
81.7 million) it currently hosts about a tenth as many trials.
An abundance of accessible participants
Beyond raw numbers, it is the accessibility of would-be participants that differentiates the region.
In a 2010 survey conducted by PricewaterhouseCoopers, 97% of sponsor respondents cited
population and efficient participant recruitment as the primary reason they chose Poland as a trial
site. 1
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CEE residents are often eager to participate in research studies because trials provide access to
advanced therapies and to service that can be difficult to attain under the various nations’ standard
health care systems. Because many patients are under treated, they are free from confounding
medications that could preclude them from trial participation. Additionally, pockets of the region
have especially high rates of certain conditions, which facilitate trial recruitment in those areas.
Poland, for example, has high cancer rates.
Much of the CEE population is concentrated in large urban centers such as Moscow (nearly 12
mln), Saint Petersburg (5 mln), Kiev (2.8 mln), Warsaw (1.8 mln) and Budapest (1.7 mln). These cities
are home to the large, therapeutically specialized hospitals that characterize the centralized public
healthcare systems in the CEE. The hospitals provide a critical referral network for trials as well as
comprehensive patient records.
Collectively, these forces speed and facilitate participant enrollment. One study that analyzed
enrollment data from 50 international phase II and III clinical trials estimated that site productivity
(measured as monthly enrollment per site) in Russia, Ukraine, and the Balkans is more than twice
that of Western Europe and the United States. 2
These same trends promote easier long-term follow-up and lower drop out rates. Residents of CEE
states tend to be less mobile than those of Western countries and the availability of patients’ medical
histories is also associated with lower screening failure and premature withdrawal rates. 3
Logistical appeal
Clinical activity in the CEE countries is concentrated in the major cities, which are easily accessible
by air and rail. These urban hubs likewise offer a network of service providers, such as translation
services and warehouses. Many of these services have emerged to meet the demands of the growing
research market.
Unlike emerging markets in China or India, research sites in CEE are in the same or proximate
time zones as major cities in Western Europe and are only a short plane ride away. That proximity
promotes communication across trial sites, which can enhance overall trial efficiency.
Qualified investigators, data quality
CEE countries have a reputation for conducting high quality clinical research due in part to a cadre of
highly trained investigators and an emphasis on data quality. Solid training facilities and progressive
attitudes toward education in the region have produced a highly qualified cadre of investigators.
What’s more, with the steady increase of clinical trial activity in countries such as Poland over the
last two decades, investigators have developed extensive experience.
Research based on FDA inspections during Investigational New Drug studies from 1994 (when the
FDA first performed inspections in CEE) and 2010 found CEE sites out performed U.S. and Western
European sites in terms of regulatory compliance and data quality. In analyzing nearly 4,900 routine
data audit inspections, from the various regions researchers found CEE sites had fewer deficiencies
per inspection (0.99) than the United States (1.59) or Western Europe (1.99). What’s more 39% of
CEE inspections found no deficiencies compared to 21.5% of inspections in the United States and
just 16.6% of those in Western Europe.
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The CEE also had the highest percentage of inspections after which no follow-up action was
indicated and the lowest percentage of inspections that required official or voluntary action. While
the data may be biased – the FDA was far more likely to conduct routine audits of U.S. sites -- the
findings support the reliability of CEE data. 5
Sources: ClinicalTrials.gov, 2/21/13; World Bank
* Member of the European Union
** Expected to join the European Union in mid 2013.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3340105/table/t4-dddt-6-053/ >>
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Standards and regulatory rigor
Ten countries in the CEE are currently part of the European Union (EU). From a sponsor’s perspective
EU membership is advantageous because countries adhere to a harmonized, familiar legislative
framework and are subject to well established EU regulations regarding Good Clinical Practice
(GCP) standards and predictable processes.
The adoption of EU standards has propelled trial activity in these countries. In the survey conducted
by PricewaterhouseCoopers, for example, 94% of sponsor respondents cited ensured EU standards
and high quality data as central to their decision to conduct trials in Poland.
Challenges remain
While CEE states present ample opportunities, sponsors new to the region
face daunting administrative, regulatory, logistical and ethical challenges.
Allying with a seasoned strategic partner with clinical experience in CEE is
essential.
Logistically it can be difficult to find central laboratories capable of addressing critical trial
requirements in a standardized manner. Conducting trials outside major cities can be prohibitive
due to lack of basic infrastructure. Identifying therapeutically excellent strategic partners with global
capabilities is a major challenge. While a proliferation of local clinical research organizations (CROs)
have cropped up throughout the region in recent years, few have the ability to coordinate CEE sites
with the balance of a global trial.
Jeremy Spivey, senior research analyst at Cutting Edge Information, a business intelligence firm
specializing in the life sciences industry, notes that site contracting in Poland is especially complex.
“If this is not handled by a CRO with a preferred vendor network it can take up to six months to get
your trial started just by your handling the contracting elements of trial sites,” he observes in a web
presentation on the topic. 6
Regulatory challenges persist as well. Even though Poland is part of the EU and subject to a 60 day
regulatory approval requirement, approvals there can still lag.
Leveraging existing site relationships is essential to addressing these
challenges. Tapping existing relationships can shorten learning curves for
all parties, expedite study start-up times, and ensure ethical conduct and
regulatory compliance.
Regulatory challenges persist as well. Even though Poland is part of the EU and subject to a 60 day
regulatory approval requirement, approvals there can still lag.
Medpace experience in CEE
Medpace has been conducting clinical trials in CEE since 2006. Our established site relationships,
specialized regulatory knowledge, therapeutic expertise and proactive approach to clinical trial
management enable us to leverage the benefits of the region while successfully navigating the
challenges.
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Medpace brings a comprehensive array of resources to bear on every clinical trial:
• Country-specific regulatory expertise. Medpace Medical Consulting (MMC) provides
comprehensive regulatory services at both the national and EU level. The MMC team has
in-depth experience working CEE authorities and addressing the entire spectrum of regulatory
requirements pertaining to submissions, quality, pre-clinical and clinical studies. By tapping
MMC’s R&D consulting services while planning studies in CEE, sponsors can avoid expensive
detours and regulatory dead ends.
• Therapeutic leadership. Medpace embeds therapeutic experts into every research
program to promote effective collaboration with sponsors and ultimately accelerate the
drug approval process. Our growing list of therapeutic specialties includes Cardiology,
Endocrine - Metabolic Disorders, Oncology, Infectious Disease and Vaccines, Nephrology,
Central Nervous System, and Regenerative Medicine.
• Longstanding site partnerships. Clinical research sites across the globe recognize
Medpace as a valued partner. The International Society for Clinical Research Sites has
twice honored Medpace with the Eagle Award in recognition of our leadership, professionalism,
integrity, passion and dedication to advancing the clinical research profession through
strong site partnerships. In addition, Medpace has been a provider for a key sponsors in need
of project rescue based on slow patient enrollment having recently stepped in with key
enrollment sites in Russia for a Phase III, Hypertriglyceridemia study.
The clinical research sites with whom we work have deep roots in their local communities.
Those ties expedite access to patients, facilitate rapid enrollment, reduce overall costs and
enable us to address local issues in a knowledgeable, culturally sensitive way. Working with
longstanding partners promotes effective communication, which is essential to managing
global research.
• Medpace Reference Laboratories (MRL). Accessing centralized lab services can be a
major challenge in CEE. Our MRL is a global leader in providing customized, high-quality
laboratory services to the pharmaceutical and biotech industries. With locations in Leuven,
Belgium; Cincinnati, Ohio; Mumbai, India; and Beijing, China, our full-service central
laboratories provide comprehensive, flexible laboratory services that maintain uniform
instrumentation, reagents, calibration, and standard operating procedures (SOPs), essential
to ensuring consist research quality.
• Technologic advantages. ClinTrak ® , Medpace’s proprietary suite of innovative
technologies, provides sponsors and study managers with real-time access to critical study
data, including laboratory and imaging results, from around the globe. When conducting
studies in multiple countries in CEE, robust technology like ClinTrak is critical for project
management and communication.
• Global technology platform. Our web-based, clinical trial technology platform improves
operational efficiencies through consistent data and tracking regarding site performance,
patient randomization, study enrollment, drug shipment tracking, specimen handling, and
data and query. This capability is particularly advantageous when running trials across
multiple countries.
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Conclusions
Clinical trial activity in CEE, which has been building for years, is poised to accelerate. The countries
of CEE offer such favorable conditions in terms of participant accessibility, large population pools,
investigator quality, low costs and manageable logistics that sponsors interested in trial efficiency
must consider them as site options. In doing so, however, sponsors must rely on experienced
strategic partners. Successful clinical research in CEE depends on specialized understanding of
the local market and regulatory climate and the ability to coordinate and manage local sites in the
broader context of the global research process. Strategic research partners must have finely tuned
local and global capabilities to overcome the myriad challenges of conducting trials in CEE and
maximize their full potential.
Sources:
1, 4
PriceWaterhouseCoopers. Clinical Trials in Poland: Key Challenges. November 2010
2
Tassignon J-P, Sinackevich N. Speeding the critical path. Applied Clinical Trials. 2004;13(1):42–48.
3, 5
Caldron PH, Gavrilova SI and Kropf S. 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 Design, Development and
Therapy. 2012;6: 53–60. Published online 2012 March 27. The authors identified CEE countries as
Bulgaria, Czech Republic, Croatia, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, Russia,
Slovenia, Serbia and Ukraine. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3340105/#b2-dddt-6-
053#b2-dddt-6-053
6, 7
CEInsights: Conducting Clinical Trials in Central and Eastern Europe.
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