Global clinical research opportunities and challenges. Example of Hungary- clinical trials growth, data quality, ethics approvals, investigator landscape

1. Clinical Rubik’s
Cube
Opportunities and
Challenges in Global R&D
Studies:
Example of Hungary
Dr. Aleksandar Skuban2009

2. Opportunities
multiply
as they are
seized.
Sun Tzu

3. Topics
Global trends in placement of clinical trials
Growing opportunities
Example of Hungary: tradition of research
Contributions
Health Atlas 2008
Patient Benefits
Future Prospects

4. Pharmaceutical
Clinical Development Psychiatry
Intl Clinical Trials Management
Clinical Research Organizations
Top 10 Global Companies
Hungary
Semmelweis University Budapest
Background
Europe and United States

5. Placement of Clinical Trials
Emerging, Developing and Mature Markets

6. Investigator Landscape
*Glickman S W. Ethical and Scientific Implications of the Globalization of Clinical research.
N Engl J Med 2009;360:816-823
Tufts Center for the Study of Drug Development

7. CRO Market 2005
15.7
14.9
6.6
L10 MM SM
Annual Revenue Growth
2002-2007
80%
11%
9%
Largest 10 CROs Medium CROs
Small Companies
Applied Clinical Trials May 2007

8. Globalization is a Tool
(and two-way road)
Rapidly Changing environment
Definitions of Emerging, Developing or Developed
Countries
Economy (GDP, IFC, World Bank)
Scientific and Ethics Standards
International Exposure
BRIC(M) and Beyond

9. And a knowledge to use it
(by all parties)
Regional Differences and Expectations
Benefit for Clinical Development Programs
New Enthusiasm for Problem-Solving

11. Regional Considerations
Patient Access
Competent Sites
Disease Prevalence
Recruitment Speed
Data Quality
Cost
Experience

12. Universal Challenges
Ethical
Scientific
Access to Health Care
Access to Tested Therapies
Commercialization
Lack of Experience
Exploitation
Data Quality
Glickman S W. Ethical and Scientific Implications of the Globalization of Clinical research. N Engl J
Med 2009;360:816-823
Shuchman M. Commercializing clinical trials-risks and benefits of the CRO boom. N Engl J Med
2007;357:1365-8

13. Tailored Solutions
Open Mind for a Changing Landscape
Value creation vs. Consumer Expansion
Country Specific Consideration and Assessment
Training
Infrastructure
ICH-GCP
Regulatory oversight

14. Hungarian Example
CEE, EU, Emerging, Developing
Discovered, Re-discovered

15. Strong Background in Science, Chemistry and
Medicine
Tradition of Pharmaceutical Manufacturing
Pharmacology Research
Established Regulatory Framework
Centralized Health Care System
Comprehensive Public Health Policies
Traditional Strengths

16. Albert Szent-Györgyi von Nagyrápolt
Nobel Prize in Physiology or Medicine in 1937.
First to isolate Vitamin C which he found in abundance in
Hungarian paprika.
Science, Chemistry
and Medicine

17. 1965 First publication by Joseph Knoll in English
1967 Psychiatrist Ervin Varga observed antidepressant
action
1971 Selective MAO-B inhibitor
1975 W Birkmayer (Wiena) Effect in PD
1996 Adjuvant Therapy in Parkinson’s Disease (US)
2006 Selegiline patch for depression (US)
Selegiline Story

18. Am J Psychiatry 1979; 136:196-199
Copyright © 1979 by American Psychiatric Association
Comparative efficacy of tofisopam and placebo
HL Goldberg and RJ Finnerty
Tofisopam is a new agent marketed in Europe as a minor tranquilizer.
The authors conducted a 4-week double-blind trial of this drug compared
with placebo in 57 outpatients with anxiety and depression. They found
that according to physician ratings and patient self-ratings tofisopam was
an effective anxiolytic agent for subjects with anxiety and depression.
Twenty-one percent of the patients receiving tofisopam and 10% of those
receiving placebo reported side effects. The drug was especially effective
in the treatment of somatic difficulties.
1970s Tofisopam (Grandaxin®)

19. Lawrenceville, NJ (June 14, 2002)
VelaPharm Advances Development of Tofisopam
for the Treatment of Anxiety in the U.S.
Preclinical Data Presented at NCDEU, a National Institute of Mental
Health/New Clinical Drug Evaluation Unit (NCDEU) General Meeting in
Boca Raton, Florida
March 14, 2006
Pharmos to buy Vela Pharmaceuticals for $29.7M
Once the deal is complete, the new company's lead product will be R-
tofisopam, a drug that has demonstrated positive Phase II data for the
treatment of diarrhea-predominant and alternating-type irritable bowel
syndrome (IBS).
R-Tofisopam in Development Today

20. 1901
1912
1913
Pharmaceutical Industry
1990 Hungarian Pharmaceutical Manufacturers
Association (MAGYOSZ)

21. Ministry of Health (2005)
OGYI (National Institute of Pharmacy)
ETT (Medical Research Council)
TUKEB (Scientific and Research Ethics Committee)
KFEB (Clinical Pharmacology Ethics Committee)
ECRIN ( European Clinical Research Infrastructures
Network)
Regulatory Framework
Professional Networks

22. 11-12 meetings per year
414 new clinical trials reviewed
1294 “amendments” reviewed
Decisions taken
70% approved
15% declined (68 % scientific, 18% ICF, 17% both)
15% withdrawn
Clinical Pharmacology Ethics
Committee (2008)

23. 1994 GCP in Hungary
2001 Clinical Trial Management Society Hungary
Founding assembly 23 organizations
2004 Membership in IFAPP International Federation of
Association of Pharmaceutical Physicians
2004 CRA accepted as a profession
2004 Hungary EU member
Professional Networks
Regulatory Framework

24. Health care expenditure
8.1
7.9
11.5
6
7.9
2560
1308
4011
583
2179
United Kingdom*
Hungary
Switzerland
Russian Federation
Greece
US$ PPP2 % of GDP

25. Number of nurses and physicians and
hospital beds
213
304
397
431
500
499
896
833
806
338
390
792
568
966
473
United Kingdom*
Hungary
Switzerland
Russian Federation
Greece
Hospital beds Nurses Physicians
Per 100 000 population (* UK data from 2002)

26. Leading physicians and Institutions
Early adoption of GCP guidelines
Excellent Data Quality
High Patient recruitment
Skilled clinical research professionals
Lower cost
Enthusiasm for novel drug development
Contributions in the ‘90s

27. Clinical Trials in Hungary
1992-2008
0
50
100
150
200
250
300
350
Phase I Phase II Phase III Phase IV Bioequiv.
Courtesy of Janos Antal, MD, MBA (Parexel Hungary)

28. New Global Trials Initiated in CEE*
146
213 196
62 47
204
573
725
212
375
Hungary Poland Russia Romania Ukraine
2002 2007
Center Watch Data August 2008 (*selected countries)

29. Atlas of Health 2008 in Europe
(WHO Europe)
Benefit for patients and patient
access benefits

30. Atlas of Health 2008 in Europe
Hungary
1st All Cancer , Lung cancer & New Cases
2nd Digestive system
3rd Colon
4th Total alcohol consumption
5th Suicide
Russian Federation (life expectancy at birth, death from all causes,
circulatory system, ischaemic heart disease (25-64), suicide)

31. Deaths from diseases of the circulatory
system
301.2
175.3
28.6
157.1
47.8
4.9
Russian Federation
Hungary
France
Females Males
Per 100 000 population (25-64 years)

32. Deaths from cancer
224.5
301.2
86.8
123.3
157.1
102.5
Russian Federation
Hungary
Sweden
Females Males
Per 100 000 population (25-64 years)

33. Deaths from lung cancer
72
99.7
16.9
20.9
35.3
19.7
Poland
Hungary
Sweden
Females Males
Per 100 000 population (25-64 years)

34. Deaths from GI system diseases
19.3
105.4
156.9
15
42.4
115.4
Norway
Hungary
Moldova
Females Males
Per 100 000 population (25-64 years)

35. Hungary Activity Map
(www.clinicaltrials.gov) October 2009
278 active studies
89 cancer studies
21 lung cancer studies

36. Prospects for clinical research
in Hungary
Slightly smaller than Indiana- population 9.9 M
Local, Regional CROs and Pharmaceutical Companies
Competition for Qualified Sites and Patients
Restrictions for Placebo-Controlled Studies

37. Opportunities
European Integration
Government Support for Clinical Research
Expanding Research Networks and Quality Sites
Accreditation of Phase I (Clinical Pharmacology) sites
Need for more qualified, English speaking personnel
Adjustment to new trends

38. Expansion
Maturing
Saturation
Migration
Future scenarios

39. Other (New)Countries and Regions

40. Growth Rate of New Global Trials
Initiated in CEE*
Center Watch Data August 2008 (*selected countries)

41. Unique
1.1B
2%221 trials in 2007 (Reuters Jan 21,2009)

42. Technology
Competition
Integration
Outsourcing
Relationships

43. choice integrity
knowledge

44. National Institute of Pharmacy http://www.ogyi.hu
Ministry of Health http://www.eum.hu/main.php
Medical Research Council http://www.ett.hu/
Clinical Trial Management Society Hungary
http://www.mkvt.hu/
http://www.mkvt.hu/admin/data/file/177_clinical_trial_managem
entsociety_hungary.pdf
Hungarian Pharmaceutical Manufacturers Organization
http://www.magyosz.org/
European Clinical Research Infrastructures Network
http://www.ecrin.org/
Useful Links

45. Thank You
Questions