Article about performing clinical research in Eastern Europe

1. ict Global Outsourcing
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A Home for Trials: the Bloc Reborn
300 Eastern Europe – a place for experienced sites, motivated patients and a history of success.
Richard Leach of RCT Global, LLC, takes a closer look at Russia, the largest, most populated
200
member of this research centric region
Richard Leach is Vice President and Head of Business Development for RCT-Global LLC, a CRO with
offices in Russia, Bulgaria and the US that uses a global network of regional providers to support clinical
100
research worldwide. Prior to joining RCT-Global in 2003, Richard was Director of Business Development for
PharmaNet, responsible for developing corporate relationships with key international accounts. With over
15 years’ experience in the pharmaceutical industry, he has had the pleasure of working with companies
offering international services as diverse as centralised laboratory and electrocardiogram (ECG) monitoring
to regulatory support and project management. Prior to his position at PharmaNet, Richard held numerous
positions with Covance Labs, Premier Research, and Quintiles Late Stage Development.
Eastern Europe continues to be one of the most active regions in both internal BMS audits and FDA inspections: “Overall
the world for clinical research. Since the early to mid 1990s, deficiencies were found to be far less common in Central and
pharmaceutical companies and the CROs that support them Eastern Europe than in Western Europe. Up to 10 per cent of
have run thousands of clinical trials, invested millions of BMS’ global data comes from Central and Eastern Europe. On
dollars, and opened or expanded offices throughout the region individual studies, sometimes as much as 50 per cent of the data
to accommodate unprecedented growth. Why has growth been comes from this region” (2).
so dramatic and what continues to make Eastern Europe the
second highest patient recruiting region in the world for ENROLMENT ENVIRONMENT
industry sponsored clinical trials, after the US (1)? In order to
consider this question we need to first reflect on the history of The reasons for patients within Eastern Europe to participate in
this phenomenon, and then examine how these changes affect clinical research are as varied as in other parts of the world.
the region today.
Table 1: Population Overview of Region
RESEARCH PIONEERS Population (rounded to
Country
the nearest thousand)
Research organisations focused on this region initially to
Belarus 9,755,000
supplement patient enrolment in trials where recruitment was not
Bosnia and Herzegovina 4,499,000
meeting expectations. With a population of almost 325 million,
and with large centralised health facilities offering deep pools of Bulgaria 7,726,000
potential patients, the attractiveness of the region was justified. Croatia 5,025,000
Once trials were introduced to the region, these early sponsors Czech Republic 10,265,000
and research organisations discovered site productivity, across all Estonia 1,330,000
therapeutic areas, was consistently higher than either Western Hungary 10,076,000
Europe or the US. As the region developed and more countries
Latvia 2,307,000
created central ethics committees, formed solid government
Lithuania 3,412,000
oversight and adopted legislation in support of ICH-GCP, more
investment poured into the region. However, once the early Montenegro 631,000
research pioneers successfully began submitting data generated Poland 38,128,000
from investigator sites and patients across this region, the level Republic of Macedonia 2,034,000
of interest within the industry soared. Romania 22,304,000
Russia 142,400,000
Many of these organisations are now coming to this region
Serbia 9,779,000
because of the bulk of their international patient databases.
Slovakia 5,401,000
What they have found is that the regulatory oversight and the
Slovenia 2,004,000
commitment to GCP is of the highest quality. According to
Cezary Statuch, Executive Director of Global Development Ukraine 46,481,000
Operations for Bristol-Myers Squibb, the quality of data coming Total Population 323,557,000
from Central/Eastern European sites is superb, as indicated by
36 ICT www.samedanltd.com

2. However, the idea that these patients are Figure 1: Breakdown of trial phases of the approved trials
somehow driven to research due to poverty or
lack of knowledge is based on stereotype not
10
statistics. In fact, the typical patient is well off, 31
with limited medical care and typically suffers
13 70
from a chronic ailment that is not being
effectively managed, or where western I
medicines offer better hope of cure or relief II
than their current treatment. These patients are
III
highly literate and have a strong understanding
IV
of the benefits and risk involved in their
Bioequivalence
research (3). In Eastern Europe, healthcare is a
heavily discussed and much published topic;
newspaper articles have served to educate the 104
population on new therapies and treatments.
Another reason why patients in Eastern Europe
find the risk of clinical trials acceptable is that
the medical profession in Eastern Europe is Figure 2: Breakout of trials by therapeutic area
considered to be ethically sound (1). This
environment promotes a much higher level of
60
trust between the patients and the investigators. 42
34 31
40
20 20
18
CURRENT GROWTH 20 7 9 7 7
6 5 4 5
1 3 2 4 2 1
0
Over the last 15 years, Eastern Europe has
Oncology Psychiatry
enjoyed significant benefits as a result of the Cardiovascular diseases Neurological diseases
investment made by the clinical research Infection diseases (including vaccine trials) Bioequivalence
industry. In addition to economic growth, life Allergology and immunology Endocrinology
Urology Dermatology
saving therapies and medicine have been
Gastroenterology Gynaecology
introduced, providing stronger medical care Rheumology Haematology
for its population. Pharmaceutical companies Pulmonology Anesthesiology
have set up both marketing and research Orthopaedics Ophthalmology
Surgery Other
offices to take advantage of strong economic
development, as well as the research benefits
of an informed and educated patient. In order to fully evaluate amendments added 2nd January 2000 and 30th December
and appreciate the current growth in the research environment, 2001), research has grown steadily (4). Based on information
it is easier to first examine one of the fastest growing countries. provided by the Federal Supervisory Agency for Health Care
The following, current information is from the largest and most and Social Development, in 2005 there were 447 approved
populated country in this region: Russia. trials involving 36,883 patients. In the first six months of
2006, the Ministry of Health has approved 228 trials that will
CLINICAL RESEARCH IN RUSSIA TODAY enroll 23,059 patients. Based on the growth seen just within
the first six months of the year, it is anticipated that, for the
Russia is a country of 142 million people spreading across 11 current year, there will be more than 460 trials approved in
time zones on two continents. The size of Russia may appear Russia, recruiting almost 50,000 patents. Of those already
imposing to the clinical research observer; however, the approved – 228 clinical trials so far – 148 of them are
majority of the population lives in or around major cities with multinational trials involving multiple sites for international
large medical institutions and experienced investigators. These corporations (5).
cities are easily accessible via air, rail or highway, and typically
provide medical care to populations greater than one million. On a further breakdown of the information presented for the
The two major cities currently involved in clinical research are trials approved during the first six months, the therapeutic
Moscow and St Petersburg. These two cities alone represent a areas with the most activity is oncology followed closely
population approaching 20 million and have specialised and by cardiovascular medicine and infectious disease. In a
general hospitals offering research opportunities across the further breakdown of the oncology segment: nine trials were
spectrum of therapeutic indications. for breast cancer, eight for haematology, seven for lung cancer,
three for gastric cancer, three for prostate cancer, three for
Since 1998, when Russia instituted Federal Law ‘On colorectal tumors, two for kidney cancer and seven for other
Medicinal Products’ 86-FZ, 22nd June 1998 (with oncology indications.
www.samedanltd.com ICT 37

3. Current growth in Russia is driven by many of the same factors best work within the current system in order to smoothly handle
that push clinical research in other Eastern European countries. shipments of both study drug and laboratory specimens. Having
The history of successful trial completion with high data quality a strong vested interest in the sponsors’ success ensures
has established strong sponsor confidence. There are many continued growth for their respective organisations and
drivers that have helped to build confidence in this region; the increases interest in their country across the industry.
following represent a selection of those that have played a part.
CONCLUSION
Site Experience and Commitment
Every site involved in clinical research has to be included on an Eastern Europe may be the second highest patient recruiting
approved list of sites, and submitted to the MoH with the region of the world in industry-sponsored clinical trials, but
application to perform the trial, ensuring that only experienced there is still tremendous room for growth and investment. This
investigators can participate. In order to be included on the list, region offers a patient population equal to that of the US, yet
the investigator must have two years’ clinical trials experience currently those with the opportunity to participate in studies is
and have received training in Good Clinical Practices. In far smaller. As a potential market for new medicines, the
addition, many of the sites are located in large medical opportunity will only increase as each of these nations
institutions in cities with good public transportation, allowing continues to strengthen their economy and develop an
for excellent patient access. Many of these sites, being located increasing interest in new medicines and treatments. Russia
in large medical institutions, have databases of patients with alone has a population of 142 million, yet at present less than
differing pathology that can be used to accelerate enrolment 100,000 patients participate in research over the course of a
during trial initiation and throughout the trial. In addition to year. Eastern Europe represents an unprecedented opportunity
their experience and access to patients, investigators in Eastern for pharmaceutical and biotech organisations developing new
Europe are experienced in working within the bureaucracy of medicines. The infrastructure is sound, the quality is proven and
state run healthcare, making them familiar with the large the potential is only now beginning to be fully realised. N
amounts of documentation and accustomed to processing
paperwork accurately and completely. The author can be contacted at richard.leach@cro-rct.ru
Motivated and Knowledgeable Patient Population References
As discussed already, the patient population in Eastern Europe
is educated and knowledgeable about clinical research. As a 1. Tassignon JP, BioEthics in Eastern Europe, GOR, Vol 7,
result of the current limitations of a state sponsored medical No 1, pp65-68, Spring 2005
system in transition, patients are motivated to participate in
clinical research. They see clinical trials as an opportunity to 2. Borfitz D, Expanding Opportunities in Central
receive the highest level of medical care, while having access and Eastern Europe, CenterWatch Monthly, Volume 11,
to new treatments that previously were unavailable to them. Issue 4, p5, April 2004
Due to protocol requirements, they often have more time with
their doctor than usual, and the diagnostic testing required to 3. Platonov P, Clinical Trials in Russia and Eastern
qualify patients frequently exceeds the standard practice of Europe: Recruitment Quality, International Journal of
the region. As a result, the Eastern European patient tends to Clinical Pharmacology and Therapeutics, Vol 4, No7,
be more compliant and less prone to leave a trial prior to pp277-280, 2003
study completion.
4. Russia first adopted laws for governing clinical research in
Experienced and Dedicated Service Providers 1998 with the Federal Law, ‘On Medicinal Products’, 86-FZ
The atmosphere in Russia, as in Eastern Europe, is right for dated 22nd June 1998 (with the last amendment dated
clinical research, due to experienced and committed sites, and 29th December 2004). In 1999 they incorporated ICH GCP
motivated, educated and knowledgeable patients. However there guidelines into industrial standard with the passing of OST
is another factor to consider when working in this region that 42-511-99 Rules of Clinical Trials Conduct in Russian
completes this picture: the service providers – regional CROs – Federation and further defined the law in 2003 with the
working throughout Eastern Europe are proud of their role in Decree of the Ministry of Health of RF #266 dated 19th
research and committed to the satisfaction of their customers. June 2003, titled About Approving of Clinical Practice
These service providers understand the importance of success to Rules in Russian Federation. Now the National Standard
their organisation and the country in which they work. They of Russian Federation GOST R 52379-2005 ‘Good Clinical
provide highly educated CRAs, often MDs, to interact with the Practice’ is in force. This standard is completely identical
sites providing strong monitoring support. These CROs are to ICH GCP.
experienced in working with the numerous regulatory groups,
and frequently have personal relationships that help to facilitate 5. The Federal Supervisory Agency for Health Care and Social
approval and maintain a high level of communications. Local Development site address is http://www.roszdravnadzor.ru/
providers support import and export activities, and know how to medcontrol/clinic/ind?year=2006
38 ICT www.samedanltd.com

4. General
Information
The recent growth in pharmaceutical development in the Russian Federation, Bulgaria, Romania and the
Ukraine has attracted the attention of drug development companies all over the world. Pharmaceutical and
Biotech companies along with numerous international clinical research organizations have seen the value
and have invested heavily. Everyday new offices are opening and trials are being initiated. Though this
growth can be attributed to many things from the globalization of research to increasingly friendly
regulatory environments one key element continues to drive interest, Patient Availability.
The Russian Federation, Bulgaria, Romania and the Ukraine represent a population in excess of 200 million
people. In major cities like Moscow, St. Petersburg, Novosibirsk, Sofia, Kiev and Odessa there are
numerous hospitals and scientific research centers that are highly-specialized offering hundreds of beds.
Many of these centers are pathology specific and attract patients from the local area (over 70% of the
population live in and around major population centers).
City - Country Population Global Clinical Trials, LLC (GCT) is a Regional CRO with it’s
headquarters located in Princeton, NJ and offices in Russia,
Moscow – Russia 10,000,000 Bulgaria, Romania and the Ukraine performing clinical research
St. Petersburg - services across Eastern Europe. GCT is experienced supporting
4,500,000
Russia trials across all phases of research and therapeutic areas; working
Kiev - Ukraine 3,000,000 with international clients from across the globe. Whether you are
looking for full clinical support to include site selection, monitoring,
Bucharest, Romania 2,100,000
project management, Regulatory, import/export, drug storage, and
Sofia - Bulgaria 1,200,000 medical writing; or only interested in an individual service to
All City populations have been rounded to the address an urgent need, you can count on GCT to handle your
nearest 100,000 requirements professionally and completely.
We offer a strong understanding of both local and international regulations
as well as access to 1,000s of qualified sites in numerous therapeutic Church on the Blood.
areas. The GCT data base identifies over 2,800 experienced sites St. Petersburg, Russia
throughout the region by indication and experience. Our pre-qualification
process includes a review of ICH/GCP as well as local law for each site, to
determine if additional training is required.
Our monitors and project managers are all certified clinicians experienced
in clinical research. Their relationship with each of their sites is strong and
based on mutual respect. As an organization, GCT maintains strong
ongoing relationships with the investigators and officials in the Ministry of
Health. These relationships help us to develop reliable feasibilities and stay
abreast of the changes in governmental regulations and their impact on
clinical research. Our expanded logistical services helps ensure smooth
and timely receipt of study materials and can also coordinate the shipment
and storage of laboratory and PK samples. As your “In Country Advocate”,
GCT will represent your organization with the kind of professionalism and
attention to detail you would expect from your own team, except with the
regional knowledge and local experience that can only come from years of
working within the Region. Please call us and discover the “GCT
Experience” for yourself, you won’t be disappointed.
St. Petersburg, Russia
Contact: Richard Leach Moscow, Russia
Sofia, Bulgaria
Phone: (609) 731-2225 Kiev, Ukraine
Bucharest, Romania
Princeton, USA