This document provides an overview of clinical trials in Turkey. It discusses the history and evolution of regulations governing clinical trials from the 1920s to present day. Key events include the first regulations in 1928, formation of ethics committees in 1993, and adoption of ICH-GCP guidelines in 1995. The infrastructure for clinical trials in Turkey has grown significantly in recent decades with over 100 ethics committees and several phase I centers. Inspections by regulatory authorities like the FDA and EMA have increased transparency. Current regulations aim to protect participants and uphold ethical standards in research.

1. CLINICAL TRIALS IN TURKEY
Dr. Hamdi Akan hamdiakan@gmail.com
Ankara University
Faculty of Medicine
Dept. of Hematology
Clinical Trials Unit

2. 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.

3. 3
 DRUG
 SURGERY
 MEDICAL DEVICE
 DIET
 PHYSICAL THERAPY
 DIAGNOSTIC INTERVENTION
 EDUCATION

4. Drug Development Process
GLP
GMP
GCP
Pre-clinic
1- 3 Year
Clinical trial
3- 8 Years
Post-approval
Synthesis and
Formulation
Idea
Animal/in vitro
test
Phase III
Phase IV
NDAIND
Phase II
Phase I

5. 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. 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.

7. 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

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

9.  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

10. Our rights are the result of our mistakes

11. Massengil Co.
Harold Watkins
1937
SULFONILAMIDE DISASTER

12. NOTHING RIGHT!

15. TUSKEGEE STUDY
 Started in 1932. Aimed to observe the natural course of
untreated syphilis.
 Volunteers were poor African Americans. Free medical
care was offered and they entered an observational
study without information and consent.

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

17. Kefauver–Harris Drug
Amendment ‘’Efficacy and
Safety’’
1962Frances Oldham Kelsey

19. HELSINKI DECLARATION
Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964,
and amended by the:
29th WMA General Assembly, Tokyo, Japan, October 1975
35th WMA General Assembly, Venice, Italy, October 1983
41st WMA General Assembly, Hong Kong, September 1989
48th WMA General Assembly, Somerset West, Republic of South Africa,
October 1996
52nd 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

20. 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).

21. ICH Guidelines
QSEM
Quality
Safety
Efficacy
Multidisciplinary
GCP
E6-R1

22. 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)

23. 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

24. 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’

25. 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

26. Nerium oleander case

27. 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

28. ETHICAL COMMITTEES
 The Central Ethical Committee was formed in
23/01/1993 and the first meeting was in 1994.
107 Ethical Committees in Turkey

29.  There will be a penalty of imprisonment from
one to three years for those conducting medical
experiments on human
Criminal Code
Article: 90

30. Criminal Code
Article: 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

31. Criminal Code
Article: 90
 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

32. 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.

33. 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
Geleneksel
Bitkisel Tıbbi
Ürünler
Yönetmeliği
(2010)

34. INFRASTRUCTURE OF CLINICAL
TRIALS IN TURKEY

35. 2014
 Number of Hospitals: 1528
 Number of Beds: 206.836
 Number of Medical Doctors: 135.616
 Number of specialists: 75.251

36. 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

37. 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 Medical Doctors: 135.616
Number of specialists: 75.251

38. Total 201.701

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

42. 0
5
10
15
20
25
30
35
40
45
2009 2010 2011 2012 2013 2014
2 1 1
13
29
44
Approved Medical Device Clinical Trials

43. Başvuru dosyalarının
hazırlanması
Sözleşme ve Bütçe
İthalat İzni
Dosyalarının
hazırlanması
Sağlık
Bakanlığına
Başvuru
Kontratların
tamamlanması
İthal izni için
Sağlık
Bakanlığına
başvuru
Start
Araştırma
Hastaneleri
Üniversite
Hastaneleri

44. CLINICAL RESEARCH UNIT

46. ÇAY
OCAĞI
ÇALIŞMA 4 ÇALIŞMA 5İLAÇ
ODASI
ÇALIŞMA 3 ÇALIŞMA 2 ÇALIŞMA 1
ASANSÖR
SEKRETERLİK
DOKTOR
ODASI
ANA GİRİŞ-ÇIKIŞ KAPISI
KLİNİK ARAŞTIRMA 1.KAT
SUNUMODASI
GÖNÜLLÜ
BEKLEME.
KLİNİK ARAŞTIRMA 2.KAT
GİRİŞİM
ODASI/
KAN ALMA
BİLİŞİM ODASI
ARŞİV

52. ARŞİV

53. GİRİSİM

54. BEKLEME

55. Ankara University Dept. of Hematology CR
Software

56. Database

57. SOP’s

59. 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

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

61. AUTHORITY (MoH)

62. 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)

63. 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

64. Clinical Research
Distance Learning Program

65. Clinical Research
Distance Learning Program

66. Book on
Clinical Research

67. Handbook on
GCP

68. GCP Journal

69. Clinical Research
Dictionary

70. Book on
Good Presentation Skills
Book on
Medical Publications

72. MANUSCRIPTS on CLINICAL RESEARCH
1. Patients’ Motivation about Clinical Trials: A Local Perspective from Turkey. Hakan TABAN, Osman Görkem
MURATOGLU, 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 Koyuncu
Irmak. J Clin Trials 2015, 5:2

73. TRANSPERANCY IN CLINICAL TRIALS
 Presenting information on clinical trials in a
publicly accessible database

74. Obligatory in Turkey

79. www.klinikarastirmalar.org.tr/en