clinical rubik's cube: global clinical trials in hungary

Clinical Rubik’s Cube

Opportunities and Challenges in Global R&D Studies: Example of Hungary

Dr. Aleksandar Skuban2009

Opportunities multiply

as they are seized.

Sun Tzu

Topics

Global trends in placement of clinical trialsGrowing opportunitiesExample of Hungary: tradition of researchContributionsHealth Atlas 2008Patient BenefitsFuture Prospects

PharmaceuticalClinical Development PsychiatryIntl Clinical Trials Management

Clinical Research OrganizationsTop 10 Global Companies

HungarySemmelweis University Budapest

Background Europe and United States

Placement of Clinical TrialsEmerging, Developing and Mature Markets

Investigator Landscape

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

CRO Market 2005

L10 MM SM

15.714.9

6.6

Annual Revenue Growth 2002-2007

80%

11%

9%

Largest 10 CROs Medium CROsSmall Companies

Applied Clinical Trials May 2007

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

And a knowledge to use it(by all parties)

Regional Differences and Expectations

Benefit for Clinical Development Programs

New Enthusiasm for Problem-Solving

Regional Considerations

Patient AccessCompetent SitesDisease PrevalenceRecruitment SpeedData QualityCostExperience

Universal Challenges

EthicalScientificAccess to Health CareAccess to Tested TherapiesCommercializationLack of ExperienceExploitationData Quality

Glickman S W. Ethical and Scientific Implications of the Globalization of Clinical research. N Engl J Med 2009;360:816-823Shuchman M. Commercializing clinical trials-risks and benefits of the CRO boom. N Engl J Med 2007;357:1365-8

Tailored SolutionsOpen Mind for a Changing Landscape

Value creation vs. Consumer ExpansionCountry Specific Consideration and AssessmentTraining InfrastructureICH-GCPRegulatory oversight

Hungarian Example

CEE, EU, Emerging, DevelopingDiscovered, Re-discovered

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

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

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

Am J Psychiatry 1979; 136:196-199 Copyright © 1979 by American Psychiatric Association Comparative efficacy of tofisopam and placeboHL 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®)

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 $29.7MOnce 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

1901

1912

1913

Pharmaceutical Industry

1990 Hungarian Pharmaceutical Manufacturers Association (MAGYOSZ)

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

11-12 meetings per year

414 new clinical trials reviewed

1294 “amendments” reviewed

Decisions taken

70% approved15% declined (68 % scientific, 18% ICF, 17%

both)15% withdrawn

Clinical Pharmacology Ethics Committee (2008)

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 NetworksRegulatory Framework

Health care expenditure

United Kingdom*

Hungary

Switzerland

Russian Federation

Greece

8.1

7.9

11.5

6

7.9

2560

1308

4011

583

2179

US$ PPP2 % of GDP

Number of nurses and physicians and hospital beds

United Kingdom*

Hungary

Switzerland

Russian Federation

Greece

213

304

397

431

500

499

896

833

806

338

390

792

568

966

473

Hospital beds Nurses Physicians

Per 100 000 population (* UK data from 2002)

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

Clinical Trials in Hungary 1992-2008

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

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)

New Global Trials Initiated in CEE*

Hungary Poland Russia Romania Ukraine

146213 196

62 47

204

573

725

212

375

2002 2007

Center Watch Data August 2008 (*selected countries)

Atlas of Health 2008 in Europe

(WHO Europe)

Benefit for patients and patient access benefits

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)

Deaths from diseases of the circulatory system

Russian Federation

Hungary

France

301.2

175.3

28.6

157.1

47.8

4.9

Females Males

Per 100 000 population (25-64 years)

Deaths from cancer

Russian Federation

Hungary

Sweden

224.5

301.2

86.8

123.3

157.1

102.5

Females Males

Per 100 000 population (25-64 years)

Deaths from lung cancer

Poland

Hungary

Sweden

72

99.7

16.9

20.9

35.3

19.7

Females Males

Per 100 000 population (25-64 years)

Deaths from GI system diseases

Norway

Hungary

Moldova

19.3

105.4

156.9

15

42.4

115.4

Females Males

Per 100 000 population (25-64 years)

Hungary Activity Map(www.clinicaltrials.gov) October 2009

278 active studies

89 cancer studies

21 lung cancer studies

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

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

Expansion Maturing Saturation Migration

Future scenarios

Other (New)Countries and Regions

Growth Rate of New Global Trials Initiated in CEE*

Center Watch Data August 2008 (*selected countries)

Unique

1.1B

2%221 trials in 2007 (Reuters Jan 21,2009)

Technology

Competition

Integration

Outsourcing

Relationships

choice integrity

knowledge

National Institute of Pharmacy http://www.ogyi.huMinistry of Health http://www.eum.hu/main.php Medical Research Council http://www.ett.hu/ Clinical Trial Management Society Hungaryhttp://www.mkvt.hu/http://www.mkvt.hu/admin/data/file/177_clinical_trial_managementsociety_hungary.pdfHungarian Pharmaceutical Manufacturers Organization http://www.magyosz.org/ European Clinical Research Infrastructures Networkhttp://www.ecrin.org/

Useful Links

Thank You

Questions