For postgraduate MDCU students.

1. Thira Woratanarat MD MMedSc MACE
Department of Preventive and Social Medicine,
Faculty of Medicine, Chulalongkorn University

2.  GCP: “What is in your mind?”
 Overview of drug development/clinical trial process
 What happened in the old times?
 Forms of research misconduct
 Introduction to GCP

3. การปฏิบติทาง
ั
คลินิกที่ดี
 Good Clinical Practice
 Good Clinical Research Practice การวจยทาง
ิั
คลินิกที่ดี
 Gemogelt (โกง)…Copy…Publish…

4. 1. Drug Discovery 2. Early Development
(Pre-clinical, IND, Phase I
and Early Phase II)
3. Advanced Clinical Trials
(Phase III)
5. Post-Marketing Strategies 4. Drug Registration
(Phase III-b and IV) and Approval

8.  Tuskegee trials - 1930s
 German prisoners trials - 1940s
 Harvard fraud - 1980s
 Thailand: how many?

9.  > 600 men with syphilis
 50% randomized to treatment
 50% randomized to NO TREATMENT
 Result: Untreated patients fared poorly
A significant number of patients died
 No information given to patients; no permission was
sought to withhold treatment; no clear endpoints.
 Outcome: Litigation, financial settlements
 16 May ‘97: Public apology from U.S. President Clinton;
support for lasting bioethics reforms
 “…..the definitive example of an unethical study”

10.  Objectives of various trials:
 Effect of cold, heat, chemicals on men, women
and children
 “Time to death” testing in response to stressors in
healthy “volunteers”
 Organ transplant experiments on healthy
“volunteers”
 Any information given is irrelevant because
prisoners were forced to participate
 Outcome:
 25 German scientists taken to court, 7
acquitted, 9 imprisoned, 9 given death sentence
 Nuremberg Code of 1947

11.  CV Training Fellow tutored by Dr. Eugene Braunwald,
prominent U.S. cardiologist
 Fellow fabricated study data; discovered because of
“too clean” data & intact dogs in the dumpster
 Outcome for fellow: License withdrawn; expelled
from Harvard; “blackballed” from research
 Outcome for Braunwald/Harvard: Written public
apology; retracted papers, great embarrassment
resulting from questioned credibility of past and
future work

13.  Obfuscation - The Omission of critical data or
results
 Fabrication – the actual making up of research data
and (the intent of) publishing them, sometimes
referred to as “drylabbing”
 Falsification – manipulation of research data and
processes in order to reflect or prevent a certain
result

14.  Plagiarism
 Self-plagiarism or “Multiple publication”
 Matthew effect’s intention
 Violation of ethical standards
 Ghostwriting data user

16. GCP = Regulations

17.  Regulations contained in 21 CFR Part 50, 56, and
312
 Part 50 (applies to consenting of subjects),
 Part 56 (applies to IRB responsibilities) and
 Part 312 (applies to IND submissions, sponsor
responsibility, and investigator responsibility)

18.  An international ethical & scientific quality
standard for designing, conducting, recording &
reporting human clinical studies
 EU
 Japan
 US
 Applies to registration studies that may have an
impact on safety & welfare of human subjects
 Based on the Declaration of Helsinki

19.  IRB/Ethics Committee
 Investigators
 Sponsor
 Regulatory Authorities

20. 40% 36%
34%
35% 31%
30% 27%
25%
25% 22% 22%
20% Foreign
Domestic
15% 12%
9%
10% 7% Foreign n = 36
Domestic n = 233
5%
0%
Protocol Records Consent Drug Acct AEs
DSI, 10/22/02

21. ICH: “Perfect World” for Clinical Trials

22.  A standard for the design, conduct, performance,
monitoring, auditing, recording, analyses, and
reporting of clinical trials that provides assurance
that
 the Data and Reported Results are Credible, and
Accurate, and that = Quality Data
 the Rights, Integrity, and Confidentiality of Trial
Subjects are Protected = Ethics

23. 1. Know and follow the study protocol
2. Select, train and log suitable study personnel
3. Record data carefully
4. Ensure study equipment is adequate
5. Maximise trial patients protection
6. Predict accurately and log patient recruitment
7. Meticulously document product accountability
8. Ensure timely and efficient safety reporting
9. Ensure the quality of lab evaluations
10. Maintain good trial files and archives
11. Maximise data quality
12. Keep everyone fully informed

24. 1. Know and follow the study protocol
 read it
 agree to it
 sign it
 follow it
 file it

25. 2. Select, train and log suitable study personnel
 log
 CV’s
 Information
Study Personnel Log
CV’s

26. 3. Record data carefully

27. 4. Ensure study equipment is adequate
 SCAM

28. 5. Maximise trial patients protection
 Ethics
 Consent
IEC Approval

29. 6. Predict accurately, log patient recruitment
 no guessing
 log screened and recruited patients
 patient withdrawal

30. 7. Document product accountability

31. 8. Ensure timely and efficient safety reporting
 Adverse Events
 Serious Adverse Events (ICH GCP)
 results in death
 life threatening
 requires hospitalisation
 prolongs hospitalisation
 results in disability
 congenital anomaly / birth defect

32. 9. Ensure the quality of lab evaluations

33. 10. Maintain good trial files and archives

34. 11. Maximise data quality
 Source Data Verification

35. 12. Keep everyone fully informed
 Communication

36.  Standard Operating Procedures (SOP’s)
 company specific requirements which can be replicated
 interpretation of GCP by companies
 set of rules, instructions, specific requirements

37. 1. Thou shalt write legibly
2. Thou shalt include the date and time
3. Thou shalt sign thy name
4. Thou shalt not use OUA
5. Thou shalt not alter an entry or disguise an
addition

38. 6. Thou shalt not use offensive, personal or humorous
comments
7. Thou shalt check everything written in your name –
before you sign it off
8. Results should be seen, evaluated and initialled by
the clinician before filing
9. Thou shalt make sure that someone in authority
understands these regulations
10. Thou needs to know how to manage these rules!!!!!

39.  Use qualified support staff
 Obtain informed consent
 Record information appropriately
 Protect confidentiality
 Handle investigational products appropriately
 Implement quality systems

40.  Vulnerable participants
 May have a legal representative
 Underage participants
 Must have a parent or legal guardian sign the consent
form
 Depending on the age of the subject, assent may be
required
 Problems with literacy
 A witness must be present