36 ICT www.samedanltd.com

ict Global Outsourcing

Eastern Europe continues to be one of the most active regions in

the world for clinical research. Since the early to mid 1990s,

pharmaceutical companies and the CROs that support them

have run thousands of clinical trials, invested millions of

dollars, and opened or expanded offices throughout the region

to accommodate unprecedented growth. Why has growth been

so dramatic and what continues to make Eastern Europe the

second highest patient recruiting region in the world for

industry sponsored clinical trials, after the US (1)? In order to

consider this question we need to first reflect on the history of

this phenomenon, and then examine how these changes affect

the region today.

RESEARCH PIONEERS

Research organisations focused on this region initially to

supplement patient enrolment in trials where recruitment was not

meeting expectations. With a population of almost 325 million,

and with large centralised health facilities offering deep pools of

potential patients, the attractiveness of the region was justified.

Once trials were introduced to the region, these early sponsors

and research organisations discovered site productivity, across all

therapeutic areas, was consistently higher than either Western

Europe or the US. As the region developed and more countries

created central ethics committees, formed solid government

oversight and adopted legislation in support of ICH-GCP, more

investment poured into the region. However, once the early

research pioneers successfully began submitting data generated

from investigator sites and patients across this region, the level

of interest within the industry soared.

Many of these organisations are now coming to this region

because of the bulk of their international patient databases.

What they have found is that the regulatory oversight and the

commitment to GCP is of the highest quality. According to

Cezary Statuch, Executive Director of Global Development

Operations for Bristol-Myers Squibb, the quality of data coming

from Central/Eastern European sites is superb, as indicated by

both internal BMS audits and FDA inspections: “Overall

deficiencies were found to be far less common in Central and

Eastern Europe than in Western Europe. Up to 10 per cent of

BMS’ global data comes from Central and Eastern Europe. On

individual studies, sometimes as much as 50 per cent of the data

comes from this region” (2).

ENROLMENT ENVIRONMENT

The reasons for patients within Eastern Europe to participate in

clinical research are as varied as in other parts of the world.

A Home for Trials: the Bloc Reborn400

300

200

100

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 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 clinicalresearch worldwide. Prior to joining RCT-Global in 2003, Richard was Director of Business Development forPharmaNet, responsible for developing corporate relationships with key international accounts. With over15 years’ experience in the pharmaceutical industry, he has had the pleasure of working with companiesoffering international services as diverse as centralised laboratory and electrocardiogram (ECG) monitoringto regulatory support and project management. Prior to his position at PharmaNet, Richard held numerouspositions with Covance Labs, Premier Research, and Quintiles Late Stage Development.

Country Population (rounded to the nearest thousand)

Belarus 9,755,000

Bosnia and Herzegovina 4,499,000

Bulgaria 7,726,000

Croatia 5,025,000

Czech Republic 10,265,000

Estonia 1,330,000

Hungary 10,076,000

Latvia 2,307,000

Lithuania 3,412,000

Montenegro 631,000

Poland 38,128,000

Republic of Macedonia 2,034,000

Romania 22,304,000

Russia 142,400,000

Serbia 9,779,000

Slovakia 5,401,000

Slovenia 2,004,000

Ukraine 46,481,000

Total Population 323,557,000

Table 1: Population Overview of Region

ICT 37www.samedanltd.com

However, the idea that these patients are

somehow driven to research due to poverty or

lack of knowledge is based on stereotype not

statistics. In fact, the typical patient is well off,

with limited medical care and typically suffers

from a chronic ailment that is not being

effectively managed, or where western

medicines offer better hope of cure or relief

than their current treatment. These patients are

highly literate and have a strong understanding

of the benefits and risk involved in their

research (3). In Eastern Europe, healthcare is a

heavily discussed and much published topic;

newspaper articles have served to educate the

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

considered to be ethically sound (1). This

environment promotes a much higher level of

trust between the patients and the investigators.

CURRENT GROWTH

Over the last 15 years, Eastern Europe has

enjoyed significant benefits as a result of the

investment made by the clinical research

industry. In addition to economic growth, life

saving therapies and medicine have been

introduced, providing stronger medical care

for its population. Pharmaceutical companies

have set up both marketing and research

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

and appreciate the current growth in the research environment,

it is easier to first examine one of the fastest growing countries.

The following, current information is from the largest and most

populated country in this region: Russia.

CLINICAL RESEARCH IN RUSSIA TODAY

Russia is a country of 142 million people spreading across 11

time zones on two continents. The size of Russia may appear

imposing to the clinical research observer; however, the

majority of the population lives in or around major cities with

large medical institutions and experienced investigators. These

cities are easily accessible via air, rail or highway, and typically

provide medical care to populations greater than one million.

The two major cities currently involved in clinical research are

Moscow and St Petersburg. These two cities alone represent a

population approaching 20 million and have specialised and

general hospitals offering research opportunities across the

spectrum of therapeutic indications.

Since 1998, when Russia instituted Federal Law ‘On

Medicinal Products’ 86-FZ, 22nd June 1998 (with

amendments added 2nd January 2000 and 30th December

2001), research has grown steadily (4). Based on information

provided by the Federal Supervisory Agency for Health Care

and Social Development, in 2005 there were 447 approved

trials involving 36,883 patients. In the first six months of

2006, the Ministry of Health has approved 228 trials that will

enroll 23,059 patients. Based on the growth seen just within

the first six months of the year, it is anticipated that, for the

current year, there will be more than 460 trials approved in

Russia, recruiting almost 50,000 patents. Of those already

approved – 228 clinical trials so far – 148 of them are

multinational trials involving multiple sites for international

corporations (5).

On a further breakdown of the information presented for the

trials approved during the first six months, the therapeutic

areas with the most activity is oncology followed closely

by cardiovascular medicine and infectious disease. In a

further breakdown of the oncology segment: nine trials were

for breast cancer, eight for haematology, seven for lung cancer,

three for gastric cancer, three for prostate cancer, three for

colorectal tumors, two for kidney cancer and seven for other

oncology indications.

Oncology

Cardiovascular diseases

Infection diseases (including vaccine trials)

Allergology and immunology

Urology

Gastroenterology

Rheumology

Pulmonology

Orthopaedics

Surgery

Psychiatry

Neurological diseases

Bioequivalence

Endocrinology

Dermatology

Gynaecology

Haematology

Anesthesiology

Ophthalmology

Other

Figure 1: Breakdown of trial phases of the approved trials

Figure 2: Breakout of trials by therapeutic area

I

II

III

IV

Bioequivalence

1031

13

104

60

40

20

0

70

42

18

31

6

20

5 49

17

37

2 4 52 1

20

34

7

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Current growth in Russia is driven by many of the same factors

that push clinical research in other Eastern European countries.

The history of successful trial completion with high data quality

has established strong sponsor confidence. There are many

drivers that have helped to build confidence in this region; the

following represent a selection of those that have played a part.

Site Experience and Commitment

Every site involved in clinical research has to be included on an

approved list of sites, and submitted to the MoH with the

application to perform the trial, ensuring that only experienced

investigators can participate. In order to be included on the list,

the investigator must have two years’ clinical trials experience

and have received training in Good Clinical Practices. In

addition, many of the sites are located in large medical

institutions in cities with good public transportation, allowing

for excellent patient access. Many of these sites, being located

in large medical institutions, have databases of patients with

differing pathology that can be used to accelerate enrolment

during trial initiation and throughout the trial. In addition to

their experience and access to patients, investigators in Eastern

Europe are experienced in working within the bureaucracy of

state run healthcare, making them familiar with the large

amounts of documentation and accustomed to processing

paperwork accurately and completely.

Motivated and Knowledgeable Patient Population

As discussed already, the patient population in Eastern Europe

is educated and knowledgeable about clinical research. As a

result of the current limitations of a state sponsored medical

system in transition, patients are motivated to participate in

clinical research. They see clinical trials as an opportunity to

receive the highest level of medical care, while having access

to new treatments that previously were unavailable to them.

Due to protocol requirements, they often have more time with

their doctor than usual, and the diagnostic testing required to

qualify patients frequently exceeds the standard practice of

the region. As a result, the Eastern European patient tends to

be more compliant and less prone to leave a trial prior to

study completion.

Experienced and Dedicated Service Providers

The atmosphere in Russia, as in Eastern Europe, is right for

clinical research, due to experienced and committed sites, and

motivated, educated and knowledgeable patients. However there

is another factor to consider when working in this region that

completes this picture: the service providers – regional CROs –

working throughout Eastern Europe are proud of their role in

research and committed to the satisfaction of their customers.

These service providers understand the importance of success to

their organisation and the country in which they work. They

provide highly educated CRAs, often MDs, to interact with the

sites providing strong monitoring support. These CROs are

experienced in working with the numerous regulatory groups,

and frequently have personal relationships that help to facilitate

approval and maintain a high level of communications. Local

providers support import and export activities, and know how to

best work within the current system in order to smoothly handle

shipments of both study drug and laboratory specimens. Having

a strong vested interest in the sponsors’ success ensures

continued growth for their respective organisations and

increases interest in their country across the industry.

CONCLUSION

Eastern Europe may be the second highest patient recruiting

region of the world in industry-sponsored clinical trials, but

there is still tremendous room for growth and investment. This

region offers a patient population equal to that of the US, yet

currently those with the opportunity to participate in studies is

far smaller. As a potential market for new medicines, the

opportunity will only increase as each of these nations

continues to strengthen their economy and develop an

increasing interest in new medicines and treatments. Russia

alone has a population of 142 million, yet at present less than

100,000 patients participate in research over the course of a

year. Eastern Europe represents an unprecedented opportunity

for pharmaceutical and biotech organisations developing new

medicines. The infrastructure is sound, the quality is proven and

the potential is only now beginning to be fully realised. �

The author can be contacted at richard.leach@cro-rct.ru

References

1. Tassignon JP, BioEthics in Eastern Europe, GOR, Vol 7,

No 1, pp65-68, Spring 2005

2. Borfitz D, Expanding Opportunities in Central

and Eastern Europe, CenterWatch Monthly, Volume 11,

Issue 4, p5, April 2004

3. Platonov P, Clinical Trials in Russia and Eastern

Europe: Recruitment Quality, International Journal ofClinical Pharmacology and Therapeutics, Vol 4, No7,

pp277-280, 2003

4. Russia first adopted laws for governing clinical research in

1998 with the Federal Law, ‘On Medicinal Products’, 86-FZ

dated 22nd June 1998 (with the last amendment dated

29th December 2004). In 1999 they incorporated ICH GCP

guidelines into industrial standard with the passing of OST

42-511-99 Rules of Clinical Trials Conduct in RussianFederation and further defined the law in 2003 with the

Decree of the Ministry of Health of RF #266 dated 19th

June 2003, titled About Approving of Clinical PracticeRules in Russian Federation. Now the National Standard

of Russian Federation GOST R 52379-2005 ‘Good Clinical

Practice’ is in force. This standard is completely identical

to ICH GCP.

5. The Federal Supervisory Agency for Health Care and Social

Development site address is http://www.roszdravnadzor.ru/

medcontrol/clinic/ind?year=2006

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Contact: Richard Leach Phone: (609) 731-2225

St. Petersburg, RussiaMoscow, Russia

Sofia, BulgariaKiev, Ukraine

Bucharest, RomaniaPrinceton, USA

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).

Global Clinical Trials, LLC (GCT) is a Regional CRO with it’s headquarters located in Princeton, NJ and offices in Russia, Bulgaria, Romania and the Ukraine performing clinical research services across Eastern Europe. GCT is experienced supporting trials across all phases of research and therapeutic areas; working with international clients from across the globe. Whether you are looking for full clinical support to include site selection, monitoring, project management, Regulatory, import/export, drug storage, and medical writing; or only interested in an individual service to address an urgent need, you can count on GCT to handle your 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 areas. The GCT data base identifies over 2,800 experienced sites 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.

City - Country Population Moscow – Russia 10,000,000 St. Petersburg -

Russia 4,500,000

Kiev - Ukraine 3,000,000 Bucharest, Romania 2,100,000

Sofia - Bulgaria 1,200,000 All City populations have been rounded to the

nearest 100,000

Church on the Blood. St. Petersburg, Russia