turkiyede klinik arastirma 2015 ing

CLINICAL TRIALS IN TURKEY

Dr. Hamdi Akan [email protected] University Faculty of MedicineDept. of HematologyClinical Trials Unit

What is a Clinical Trial?

A prospective trial, done with the purpose of comparing the effect and value of an intervention with the control group in a clinical situation, is called a

Friedman LM, Furberg CD, DeMets DL: Fundamentals of Clinical Trials (2nd edition). St. Louis, Mosby 1985.

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DRUG

SURGERY

MEDICAL DEVICE

DIET

PHYSICAL THERAPY

DIAGNOSTIC INTERVENTION

EDUCATION

Drug Development Process

GLP

GMP

GCP

Pre-clinic1- 3 Year

Clinical trial3- 8 Years

Post-approval

Synthesis and Formulation

Idea

Animal/in vitrotest

Phase III

Phase IV

NDAIND

Phase II

Phase I

5

Daily medical practice aims to gain a benefit to a patient by treating.

Clinical research aims to find a scientific answer that may help future patients.

6

Although scientific rules regulate the daily medical practice, they can be modified when necessary.

Clinical research has to be performed according to previously defined rules and regulations. To deviate from them can be acceptable for the benefit of the patient but may be wrong on behalf of the clinical research.

SCORBUT

A big problem for the English army in 1700’s.

James Lind separated 12 sailors in 6 groups. They all received the same diet plus; Vinegar

Diluted sulfuric acid

Apple vinegar

Garlic, radish

2 Orange and 1 lemon

No addition

SEMMELWEIS

The mortality rates in the clinic dropped form 18.3% to 1.3% after hand washing of the medical students.

No one believed him

Fired after 1 year

Went back to Budapest and conducted a new study

Mortality decreased to 1% from 15%

Vienna Medical Journal refused the paper summarizing his results

Our rights are the result of our mistakes

Massengil Co.

Harold Watkins

1937

SULFONILAMIDE DISASTER

NOTHING RIGHT!

TUSKEGEE STUDY

Started in 1932. Aimed to observe the natural course ofuntreated syphilis.

Volunteers were poor African Americans. Free medicalcare was offered and they entered an observationalstudy without information and consent.

The study was terminated in 1972; 20 years after the discovery of teheffectiveness of Penicillin in syphilis. New York Times reported this as teh‘’longest study in medical history, performed on humans without anytreatment’’.

Kefauver–Harris Drug Amendment ‘’Efficacy and

Safety’’

1962Frances Oldham Kelsey

HELSINKI DECLARATION

Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964, and amended by the:

29th WMA General Assembly, Tokyo, Japan, October 197535th WMA General Assembly, Venice, Italy, October 1983

41st WMA General Assembly, Hong Kong, September 198948th WMA General Assembly, Somerset West, Republic of South Africa,

October 199652nd WMA General Assembly, Edinburgh, Scotland, October 2000

53rd WMA General Assembly, Washington 2002 (Note of Clarification on paragraph 29 added)

55th WMA General Assembly, Tokyo 2004 (Note of Clarification on Paragraph 30 added)

59th WMA General Assembly, Seoul, October 2008

1964

ICH-GCP

1980 – Harmonization of regulations in Europe

1989 – Europe, Japan and USA joining forces

1990 April - ICH meeting in Brussels

Partners:

European Commission, European Medicines Agency (EMEA), European Federation of Pharmaceutical Industries and Associations

(EFPIA), JapanMinistry of Health, Labour and Welfare, Japan Pharmaceutical Manufacturers Association (JPMA), Food and Drug Administration (FDA), Pharmaceutical Research and Manufacturers of America (PhRMA).

ICH Guidelines

QSEM

QualitySafety

Efficacy

MultidisciplinaryGCP

E6-R1

TURKEY

First Regulations:

Code of Pharmaceutical Products and Preparations -1928

Bakanlıkça İlaç İmal ve Satış İzni verilebilmesi için Tahlil ve Tetkik neticesinde formülüne uygun ve bildirilen tedavi vasıflarına haiz olması gereklidir (Madde 7.E)

TURKEY

Code of the Application of Medical Practice –1928

Article 70: All medical doctors have to get consent from the patients; and from the parents of a child for every intervention

TURKEY

The Constitutional Code– 1987

‘the scientific research with licensed or not licensed medicines on human subject cannot be done if the Ministry of Health (MOH) approval and the relevant patient’s consent are not in place’

TURKEY

Medical Deontology Bylaw – 1960

Article 10: The regulation for the Investigator to apply and to offer his/her new diagnostic and therapeutic approach.

Article 11: No medical experiment can be conducted on human, but if the available treatment options are not sufficient to benefit the patient, a conditioned permission can be granted

Nerium oleander case

30

REGULATIONS IN TURKEY

Regulation on Clinical Trials 29.01.1993

Regulation on the evaluation of Bioavailability and

Bioequivalance of pharmaceutical products

27.05.1995

Good Clinical Practice Guideline 29.12.1995

Bylaw on Patient Rights 01.08.1998

Criminal Code 2005

Bylaw on Animal Experiments 16.05.2004

ETHICAL COMMITTEES

The Central Ethical Committee was formed in 23/01/1993 and the first meeting was in 1994.

107 Ethical Committees in Turkey

There will be a penalty of imprisonment from one to three years for those conducting medical experiments on human

Criminal CodeArticle: 90


To preclude a penalty the following are mandatory:

Approval from authorities

Preclinical and animal studies

A rationale for experimenting on human from the initial scientific information

No permenant risk and harm, no pain

Evaluation of Risk/Benefit ratio

Informed Consent


The following are the requirements for medical experimentation on children not to raise criminal liability:

Same conditions for the adults

Obligatory to conduct on children

Child assent + Parent consent

A pediatrician in Ethical Committees

Türk Ceza Kanunu Madde: 90

İnsan üzerinde gerekliliklere uyulmaksızın deney yapılması sonucu:

Mağdurun yaralanması veya ölmesi halinde kasten yaralama veya kasten adam öldürme suçuna ilişkin hükümler uygulanır.

Drug

• Regulation on Clinical Trials of Medicinal and Biological Products (2014)

Medical Device

•Bylaw on Clinical Trials with medical Devices (2014)

Observational Drug Studies

•Guideline on Observational Drug Studies (2014)

Cosmetic Products

•Bylaw on Clinical trials with Cosmetic Products (2015)

Herbal Products

•Bylaw on Medical GelenekselBitkisel TıbbiÜrünlerYönetmeliği(2010)

INFRASTRUCTURE OF CLINICAL TRIALS IN TURKEY

2014

Number of Hospitals: 1528

Number of Beds: 206.836

Number of Medical Doctors: 135.616

Number of specialists: 75.251

Clinical Trials Journey of Turkey-Long and Thin Road. Hilal Ilbars, Kaan Kavaklı, Hamdi Akan, Duygu Koyuncu Irmak. J Clin Trials 2015, 5:2

Number of Hospitals: 1528

Number of Beds: 206.836


Number of Medical Doctors: 135.616

Number of specialists: 75.251

Total 201.701

0

5

10

15

20

25

30

35

40

45

2009 2010 2011 2012 2013 2014

21 1

13

29

44

Approved Medical Device Clinical Trials

Başvuru dosyalarınınhazırlanması

Sözleşme ve Bütçe

İthalat İzniDosyalarınınhazırlanması

SağlıkBakanlığına

Başvuru

Kontratlarıntamamlanması

İthal izni içinSağlık

Bakanlığınabaşvuru

Start

AraştırmaHastaneleri

ÜniversiteHastaneleri

CLINICAL RESEARCH UNIT

ÇA

Y

OC

AĞ

I

ÇALIŞMA 4 ÇALIŞMA 5İLAÇ

ODASI

ÇALIŞMA 3 ÇALIŞMA 2 ÇALIŞMA 1

ASANSÖR

SEKRETERLİK

DOKTOR

ODASI

ANA GİRİŞ-ÇIKIŞ KAPISI

KLİNİK ARAŞTIRMA 1.KAT

SU

NU

M O

DA

SI

GÖNÜLLÜ

BEKLEME.

KLİNİK ARAŞTIRMA 2.KAT

GİRİŞİM

ODASI/

KAN ALMA

BİLİŞİM ODASIARŞİV

ARŞİV

GİRİSİM

BEKLEME

Ankara University Dept. of Hematology CR Software

Database

SOP’s

PHASE I CENTERS

Ege University ARGEFAR Phase I and BA/BE Center

Ege University Medical Faculty Pediatric Hematology Phase I Center

Erciyes University Hakan Çetinsaya Phase I and BA/BE Center

Gaziantep Phase I and BA/BE Center

INSPECTIONSYIL DENETİCİ KURUM

2004 FDA Ege University, Gastroenterology İzmir

2006 FDA Istanbul University, Romatology İstanbul

2006 FDA Ege University, Pulmonary Diseases İzmir

2007 FDA Ege University, General Surgery İzmir

2007 FDA Dokuz Eylül, General Surgery İzmir

2009 EMA Ege University General Surgery İzmir

2010 FDA İstanbul University, Medical Oncology İstanbul

2013 FDA Yüzüncü Yıl, Pediatrics Van

2013 EMA Ankara University, Hematology Ankara


AUTHORITY (MoH)

NGO’s/Academic organizations

Clinical Research Association (KAD)

Istanbul Clinical Research Initiative (IKAI)

Istanbul University Clinical Research Excellence Center

Association of Contract Research Organizations (SAKDER)

Turkey Clinical Research Infrastructure Network (TUCRIN)

Association of Research-Based Pharmaceutical Companies (AIFD)

GOOD CLINICAL PRACTICE CERTIFICATION

Not legally obligatory for clinical investigator but needed to participate in a clinical trial,

Legally binding for Ethical Committee members

GCP educated health care personnel ≈ 10.000

Clinical Research Distance Learning Program

Book on Clinical Research

Handbook on GCP

GCP Journal

Clinical Research

Dictionary

Book on Good Presentation Skills

Book on Medical Publications

MANUSCRIPTS on CLINICAL RESEARCH

1. Patients’ Motivation about Clinical Trials: A Local Perspective from Turkey. Hakan TABAN, Osman GörkemMURATOGLU, Bulut GÜÇ, Abdurahim HAJYOUSSEF, Atila KARAALP. Marmara Medical Journal 2011;24:181-6

2. Turkey’s Trial Status. Hilal İlbars, Gülbin Özçelikay. GCP Journal, 2005: 17-19

3. Clinical Scientific Research Potentials in Turkey. Emin Kansu et al. Monitor 2006: 51-54

4. New GCP Rules in Turkey. Hamdi Akan et al. Monitor 2007: 41-44

5. Turkey’s Position Regarding Clinical Drug Trials. Nüket Örnek Büken. Clinical Research and Regulatory Affairs 2003: 20(3); 349–355, 2003

6. Clinical Trials in Turkey. Hilal İlbars. Turkish Journal of Hematology 2013;30:111-114

7. Transparency in Clinical Research and Status in Turkey & Middle East. Nursah O. Cetinkaya. Applied Clinical Research, Clinical Trials & Regulatory Affairs, 2015 (2)

8. Orphan Drugs: R&D Challenges with Updates from Turkey and Middle East Countries. Hilal İlbars, Duygu K. Irmak, Hamdi Akan. Journal for Clinical Studies 2014: 6(2): 58-6

9. Clinical Trials Journey of Turkey-Long and Thin Road. Hilal Ilbars, Kaan Kavakli, Hamdi Akan, Duygu KoyuncuIrmak. J Clin Trials 2015, 5:2

TRANSPERANCY IN CLINICAL TRIALS

Presenting information on clinical trials in a publicly accessible database

Obligatory in Turkey

www.klinikarastirmalar.org.tr/en

turkiyede klinik arastirma 2015 ing

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