Richard Leach is Vice Presidentand Head of Business Developmentfor Russian Clinical Trials, LLC, a

regional contract researchorganisation (CRO) located in St

Petersburg, Russia, supportingclinical research throughout Russia,the Ukraine and Bulgaria. Prior tojoining Russian Clinical Trials, MrLeach was Director of Business

Development for PharmaNet,responsible for developing

corporate relationships with keyinternational accounts. Over his 15

years in the pharmaceuticalindustry, he has worked with

companies offering internationalservices as diverse as centralisedlaboratory and electrocardiogram(ECG) monitoring to regulatory

support and project management.Prior to his position at

PharmaNet, Mr Leach heldnumerous positions with Covance

Labs, Premier Research andQuintiles Late Stage Development.

a report by

R i c h a r d L e a c h

O v e r v i ew

Investment in clinical research in Central andEastern Europe (CEE) and Russia has continued togrow at a rapid rate. Over the last few yearsinternational pharmaceutical companies andcontract research organisations (CROs) haveexpanded their local presence significantly to takeadvantage of research opportunities while reducingthe cost of their clinical programmes. Althoughlarge pharma may also be setting up theinfrastructure to take advantage of the long-termmarket potential, the near-term returns on theclinical opportunity are apparent.

For years, Eastern Europe has been a fertile groundfor clinical research due to excellent patient accessand a motivated and experienced investigator base. Now, the new CEE countries that have been soeffective are in the process of redeveloping their research standards to address the new EUClinical Directive.

As these CEE countries move towards compliancewith the new directives, sponsors and CROs alikehave increased their interest in Russia.

Ru s s i a T o d a y

The Russian Federation is a country of 145 millionpeople. Although about 65% of the population livein industrialised cities with access to government-sponsored medical care and treatment centres, thecountry has been mired in a negative populationgrowth for over 10 years.

The National Bureau of Asian Research (NBR) hasreported that in the 11 years since post-communism independence, “Russia’s populationhas declined by more than four million people orabout 3%”.1 This decline has been attributed tonumerous causes, the most dramatic being lower birth rates as a result of increased abortionrates, and the spread of sexually transmitted

diseases. When left untreated or inadequatelytreated these diseases may cause sterility. Inaddition, the high incidence of cardiovasculardisease combined with growing regional epidemics in HIV and hepatitis impact dramaticallyRussia’s ability to effect significant change to themortality rate.

Over the last 40 years cardiovascular disease (CVD)and stroke mortality rates in Japan, WesternEurope and North America have fallen verysharply. In the US, for example, the age-adjusteddecline between 1965 and 2000 was over 56%.Russia, by contrast, suffered an explosion ofcardiovascular deaths over the same period.Between 1965 and 2001, Russia’s age-standardiseddeath rate for CVD surged by 25% in women andby 65% in men.1

The increase in cardiovascular mortality has beenattributed to stress brought on by the social andeconomic changes, alcoholism, which is on the rise in both men and women, tobacco smoking and a more sedentary lifestyle with very little focuson any exercise other than walking. Because manyof the elements associated with the surgingmortality rate are connected to social behaviourand the need for education, there is little hope that the government, with its regionally limitedmedical infrastructure, will be able to incorporateenough changes to slow or stop the trend in the near future. This environment, though bleakfor Russia’s future, creates significant opportunityfor companies who want to help be part of the remedy.

Qua l i t y M ed i c a l C a r e a n d D a t a

Despite the medical care of the average Russianbeing in need of improvement, the expertise andknowledge of the doctors treating them is veryhighly regarded. Doctors in Russia must undergomedical school followed by residency and

Univer sa l Bene f i t s o f Russ ian C l in i ca l Research

Clinical Trials

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1. Eberstadt N, “The Russian Federation at the Dawn of the Twenty First Century” NBR Analysis, Volume 15, Number2, September 2004.

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speciality training. Then, at five-year intervals,every physician must take a refresher exam tocontinue their practice.

In addition, since 1991, Russian physicians havetravelled throughout the world attending workshopsand conferences to better understand Westernmedicine and practices.

The result is a highly professional and educatedinvestigator pool motivated by both financial andmedical necessity to introduce clinical research to asmany patients as possible.

In recruiting and treating patients, the Russianinvestigators have learned to follow good clinicalpractices (GCP) and the International Conferenceon Harmonization (ICH). Russia first adopted lawsfor governing clinical research in 1998 with theFederal Law on ‘Medicinal Products’ # 86-FZdated 22 June 1998 (with amendments dated 2January 2000 and 30 December 2001). In 1999,they incorporated ICH GCP guidelines into lawwith the passing of OS 42-511-99 ‘Rules of

Clinical Trials Conduct in Russian Federation’,and further defined the law in 2003 with theDecree of the Minister of Health of RF #266 dated19 June 2003, entitled ‘Good Clinical Practice inRussian Federation’.

Regulatory inspections by the US Food and DrugAdministration (FDA) of 23 investigator sites fromJanuary 1994 to March 2002 in Eastern Europe,including Russia, found all the sites to be withoutneed of official action.2

An article in CenterWatch in spring 2004 speaksdirectly to the regulatory environment and qualityof data in the CEE and Russia. “Regulatoryapproval times across regions are comparable withthose in the EU and the quality of data coming fromCEE sites is also superb, as indicated by both internalBMS audits and FDA inspections”.3

R e c r u i tmen t

Given the overall healthcare situation of Russia, itis not difficult to understand why patientenrollment continues to be so strong. Typically, thetreatment provided in clinical research is better thanthe standard of care available through the nationalhealth services.

The protocol requirements for complete physicalsand more personal interaction with the investigatormay in itself offer incentive enough to join a trial. Combined with the additional incentives of Western medicines and therapies, it is easy to see why the prospective patients are excited to participate.

Patients in Russia are both eager to participate andextremely compliant. Most patients are eitheremployed or retired with a high school educationand making an average income.4 This mix speaks to an educated patient population that has decided to participate because of a specific medicalneed. These patients tend to make all the

planned appointments and comply with treatmentas directed.

Ru s s i a n H e a l t h c a r e S y s t em

Though currently plagued with funding challenges,the Russian healthcare system still administers care tomillions of Russians daily. Their ‘Soviet’ structuredcentral healthcare system created large medicalinstitutions specialising in specific therapeutic areas.

These institutions, both general and therapeuticallyaligned, have large patient pools to draw frommaking enrollment in clinical trials very accessibleto the patient and rapid for the sponsor. Inaddition, many of the medical practices in Russia call for hospitalisation, when in the Westthe same treatment may be done in an out-patient setting.

2. Platonov P, “Clinical Trials in Russia and Eastern Europe: Recruitment Quality”, Int. J. Clin. Pharmacol. Ther.Vol. 41, No 7, 2003 pp. 277–280.

3. Borfitz D, “Expanding Opportunities in Eastern Europe” CenterWatch Monthly, Volume 11, Issue 4, April 2004.4. Varshavsky S, Platonov P, Kistkina M, “Why Do Patients Participate in Trials?”, GCPj November, 2002.

As these CEE countries move towards compliance with the

new directives, sponsors and CROs alike have increased

their interest in Russia.

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Hospital costs, as part of standard practice, do not add to the trial expenses. The additional levelof attention is helpful in informing the patients of their obligations in the trial and providing the opportunity to more closely monitor andinstruct the patients early on helping to facili-tate compliance.

It is Russian law that all patients enrolled in clinicaltrials receive an individual insurance policy.Without proof of insurance for all patients, nostudy will be approved. This insurance is importantin protecting the patients’ rights. The cost for thisinsurance is minimal when compared with the costof the trial and helps with enrollment, givingpatients more piece of mind.

Co s t - s a v i n g Oppo r t u n i t i e s

In addition to the clinical benefits of working inRussia, there are cost-saving opportunities. Man-hours are much less expensive in Russia than in theWest, so labour can be found at significantlyreduced rates.

Although some Russian CROs have begun toglobalise, and are realising the financialresponsibilities of that growth, there are still

many local CROs that can provide significantsavings in clinical fees. Experienced regional CROs can provide savings upwards of 50%,compared with those in the West, while stillproviding experienced MDs as project managersand monitors.

E v e r y o n e B e n e f i t s

The reduced cost of man-hours in addition to theincreased enrollment rates provides a greatpotential for savings. The current economic state ofRussia, struggling with change as they adapt to theWestern ideas and culture, combined with theneeds of the population praying for economicstability, and in desperate need of improvedhealthcare, makes the Russian Federation a perfectplatform for clinical research.

In Russia, Western companies are free to investtheir research dollars where they will bring thegreatest returns in the shortest period of time. Asthey invest in research, they are also investing inthe healthcare of an entire population. Thesedollars can help stabilise an economy thatultimately will join the world as a partner and withit bring Russia’s vast resources, both natural andcultural, to the world. ■

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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

St. Petersburg, Russia Moscow, Russia

Sofia, Bulgaria Kiev, Ukraine

Bucharest, Romania Princeton, NJ USA

Phone: 609-731-2225 www.gctrials.com

Experience Across Multiple Therapeutic Areas

CNS Oncology / Blood Disorders Alzheimer’s, Depression, Schizophrenia,

Attention Deficit Disorder, Multiple Sclerosis, Diabetic Neuropathic Pain

Colon, Pancreatic, Prostate, and Breast Cancers, Acute Myeloid Leukemia,

Chemo Induced Nausea and Vomiting,

Cardiovascular Ophthalmology Acute Peripheral Arterial Thrombosis, Hyper-lipidemia, Congestive Heart Failure, Ischemia,

Arteriosclerosis, Coronary Artery Disease

Acute Macular Degeneration (WET and DRY), Subfoveal Choroidal Myopia, Glaucoma, Diabetic Macular Edema

Anti-Infectives Dermatology Community Acquired Pneumonia (CAP), AIDS

HIV Induced Diarrhea, Hepatitis C, Streptococcus pneumonia, Helicobacter pylori

(H. pylori), Urinary Tract Infections

ACNE, Psoriasis, Rosacea, Herpes simplex

Metabolic / Endocrinology Other Studies Type I and Type II Diabetes, Diabetic Foot Ulcer, Rheumatoid Arthritis, Osteoporosis,

Gastroenterology, Diabetic Neuropathy

Surgical Pain, Acute Viral Rhinitis, Stomach Ulcers, Gastric Intestinal

Reflux Testimonials: “Our organization didn’t have experience working in this region of the world so our team was a little anxious. It wasn’t long however before we realized our fears were unfounded. GCT handled everything professionally and completely. They expedited the regulatory process and handled the importation of study drug from beginning to end. GCT made our first experience in Russia a huge success.”

President, US Biotech “This was our second time working with GCT and they impressed us even more the second time around. With the deadline looming for submission prior to summer holiday, GCT worked tirelessly to create the submission package and manage all the translations necessary for us to get approval on time. From that point on we knew we had a team that understood the value of time and could get the job done!”

Director, Clinical Operations, US Pharmaceutical Company “The support GCT provided in helping us get started was incredible. We found the staff to be very customer friendly, and professional. Our project manager, a cardiologist himself, knew every detail about the protocol and the patient population. We found GCT dependable and extremely easy to work with.” V.P. European Operations, Global CRO