Presentation outlining the importance of ethics while conducting clinical research

1. GOOD CLINICAL PRACTICES
DR. KARUN KUMAR
JUNIOR RESIDENT – I
DEPT. OF PHARMACOLOGY

2. What is Clinical Research ?
•Research conducted on
•Human subjects or
•Material of human origin
•Tissues,
•Specimens, and
•Cognitive phenomena
http://keck.usc.edu/Research/Clinical_Research/Definition.aspx

3. What is Clinical Trial ?
•Scientific studies
•Test the effectiveness of
•Treatment,
•Device, or
•Drug
•Find new & better ways
http://keck.usc.edu/en/Research/Clinical_Research/Clinical_Trials.aspx

4. Phases of Clinical Trial
Phase Primary goal Dose Patient monitor
Number of
participants
Preclinic
al
Testing of drug in non-
human subjects
Unrestricted
A graduate level
researcher-Ph.D.
In vitro & in vivo
animal models
Phase 0
Oral bioavailability & half-
life of drug
Subtherapeutic
Clinical
researcher
10 people
Phase I
Testing of drug on healthy
volunteers (safety)
Subtherapeutic
with asc. Doses
Clinical
researcher
20-100
Phase II
Testing of drug on patients
(efficacy & tolerability)
Therapeutic dose
Clinical
researcher
100-300
Phase III
Testing of drug on pts.
(confirm efficacy)
Therapeutic dose
Clinical research.
& Physician
1000-2000
Phase IV
Post-marketing
surveillance (A/E, D-D I)
Therapeutic dose Physician
Anyone seeking
treatment
Phase V Translational research No dosing None All reported use
DeMets D., Friedman, L., and Furberg, C.,(2010).Fundamentals of Clinical Trials.Springer 4th Edition
Goodman and Gilman's The Pharmacological Basis of Therapeutics, (2011) 12th Edition

6. What are Good Clinical Practices ?
•More than any one document
•Collective compilation of many
•thoughts,
•ideas and
•learning moments
spanning the globe over

7. •International ethical and
scientific quality standard for
•Design,
•Conduct,
•Performance,
•Monitoring,
•Auditing,
•Recording,
•Analysis, and
•Reporting
of clinical trials

8. Historical Background
Year Event
460 B.C. Oath of Hippocrates
1930's U.S. Food, Drugs and Cosmetic Act
1947 Nuremberg Code
Dec. 10th 1948 Declaration of Human Rights
1962 Kefauver-Harris Amendment
1964 Declaration of Helsinki
1979 The Belmont Report
1982 International Guidelines for Biomedical Research Involving
Human Subjects (WHO & CIOMS)
1996 ICH-GCP guidelines issued
1997 ICH-GCP guidelines implemented
Vijayananthan A, Nawawi O.The importance of Good Clinical Practice guidelines
and its role in clinical trials.Biomed Imaging Interv J. 2008 Jan-Mar; 4(1).

12. The death sentences imposed in
October 1946 were carried out by
Master Sergeant John C. Woods
(1903-50), who told a reporter from
Time magazine that he was proud of
his work. "The way I look at this
hanging job, somebody has to do it .
. . ten men in 103 minutes. That's
fast work."
http://www.history.com/topics/world-war-ii/nuremberg-trials

13. Brigadier General Telford Taylor, Chief of Counsel,
during the Doctors Trial, which was held in
Nuremberg, Germany, from December 9, 1946, to
August 20, 1947.

14. During testimony at the Doctors Trial, American
medical expert Dr. Leo Alexander points to scars on
Jadwiga Dzido’s leg. Dzido, a member of the Polish
underground, was a victim of medical experiments at
the Ravensbrüeck concentration camp. Nuremberg,
Germany, December 22, 1946.

15. Nazi physician Carl Clauberg who performed medical
experiments on prisoners in Block 10 of the
Auschwitz camp. Poland, between 1941 and 1944.

16. A prisoner in a compression chamber loses
consciousness (and later dies) during an experiment
to determine altitudes at which aircraft crews could
survive without oxygen. Dachau, Germany, 1942.

17. Victim of a medical experiment immersed in freezing
water at the Dachau concentration camp. Dachau,
Germany, between August 1942 and May 1943.

18. A Romani (Gypsy) victim of Nazi medical experiments
to make seawater potable. Dachau concentration
camp, Germany, 1944.

19. Photo of wounds left by a medical experiment. The
victim had been burned with phosphorous so that
medicaments could be tested

20. Nuremberg Code (1947)
•Voluntary consent of the
human subject is absolutely
essential
•Favorable risk/benefit ratio
•Research must help society
•Research should be based on
previous knowledge

21. •Participant must be free to
stop at any time
•Research should not cause
mental & physical suffering
•Research should avoid risk of
injury & death

23. Declaration of Helsinki (1964)
•Well being of subject >
interest of science & society
•Consent should be in writing
•Limited use of placebo
•Greater access to benefit

24. (April, 1979)

26. Respect for persons
•Protecting autonomy of
subjects
•Treating subjects with
courtesy and respect
•Allowing for informed
consent

27. Beneficence
•The philosophy of "Do no
harm”
•Maximize benefits for the
research project
•Minimize risks to the research
subjects

28. Justice
•Ensure considered
procedures are administered
fairly
•Fair distribution between
•Burden of research (Costs)
•Benefit of research

29. Common Rule (1981)
•Describes the types of
research subject(s)
•Defines key terms such as
•Research,
•Human subject, and
•Minimal risk

30. •Sets forth requirements for
•IRB membership
•Review procedures
•Criteria for approval
•Lists requirements for
informed consent

31. Overview of Clinical research
process
Development of the trial protocol
Development of standard operating
procedures (SOPs)
Development of support systems and
tools

32. Selection of trial sites and the selection of properly
qualified, trained, and experienced investigators
and study personnel
Ethics committee review & approval of the protocol
Enrollment of subjects into the study:-
Recruitment,
Eligibility, &
Informed consent
Review by regulatory authorities

33. Safety management and reporting
Trial data acquisition: conducting the trial
The investigational product(s): quality, handling and
accounting
Monitoring the trial

34. Quality assurance of the trial
performance and data
Managing trial data
Reporting the trial

35. WHO principles for GCP
Principle 1 – Ethical Conduct
•Research involving humans
 Scientifically sound
 In accordance with
Declaration of Helsinki

36. Principle 2: Protocol
•Research
 To be described in a
•Clear,
•Detailed, and
•“Scientifically justified”
protocol

37. Principle 3: Risk Identification
•Foreseeable risks and
discomforts and any
anticipated benefit(s)
 To be identified

38. Principle 4: Benefit-Risk
Assessment
•Research initiated only if
anticipated benefit(s)
outweigh the risks
•Most important considerations
•Rights,
•Safety, and
•Well-being of trial subjects

39. Principle 5: Review by IEC/IRB
•Research should receive
independent (IEC/IRB)
approval prior to initiation

40. Principle 6: Protocol Compliance
•Research  Conducted in
compliance with the
approved protocol

41. Principle 7: Informed Consent
•To be obtained
•From every subject
•Prior to research participation
•In accordance with national
culture(s) and requirements

42. Principle 8: Continuing review /
ongoing benefit-risk assessment
•Research  Continued only if
the benefit-risk profile
remains favorable

43. Principle 9: Investigator
Qualifications
•Qualified and duly licensed
medical personnel
 Responsible for the
medical care of trial
subjects

44. Principle 10: Staff Qualifications
•Each individual involved
should be qualified by
•Education,
•Training, and
•Experience

45. Principle 11: Records
•Clinical trial information
should be
•Recorded,
•Handled, and
•Stored

46. •In a way that allows its
accurate
•Reporting,
•Interpretation, and
•Verification

47. Principle 12: Confidentiality /
Privacy
•Confidentiality of records
should be protected
•In accordance with the
applicable regulatory
requirement(s)

48. Principle 13: Good Manufacturing
Practice(s)
•Investigational products
should be
•Manufactured,
•Handled, and
•Stored
in accordance with applicable
GMP

49. Principle 14: Quality Systems
•Systems with procedures that
assure the quality of every
aspect of the trial should be
implemented
•Quality control (QC)
•Quality assurance (QA)
•Quality improvement (QI)

50. Code of Federal Regulations, Title
21
21 CFR 11: Electronic records
and signatures
21 CFR 50: Protection of
human subjects
21 CFR 54: Financial disclosure
by clinical investigators

51. 21 CFR 56: IRB that oversee
clinical trials
21 CFR 312: Investigational
New Drug Application
21 CFR 812: Investigational
Device Exemptions

53. ICH-GCP guidelines
•“Bible” of clinical trials
•Global law which safeguards
humanity
•13 core principles

54. Who is responsible for GCP ?
•Each & every person involved
in the research process.
•This includes
1.Sponsors
2.Investigators and research
staff

55. 3. Contract Research
Organizations
4. IRB/EC
5. FDA
6. Research Subject

56. Never ending debate
•Whether the "greater good"
trumps the rights of the
individual?
•Are individual’s rights what
make up the greater good?
•Is it the greater good that
allows for individual’s rights?

57. Take Home Message
•"If it wasn't documented, it
wasn't done.”
•GCP is more than a piece of
paper or a set of rules
•A mind-set of dedication that
ensures a high level of ethics
& quality in research

60. THANK YOU