Introduction to clinical research and gcp

1. Introduction to Clinical Research
and
Good Clinical Practice
Ahmed Abdelmabood Zeeneldin
MD Medical Oncology, Egypt
Master of Clinical Research, UK

2. Items to be covered
• Clinical Research
• GCP

3. Scientific Research
• Observations
• Relations
• Workers
• temperature
• car-oil change

4. Clinical Research
• Observations
• Relations
• Question? Is there a
relation between the time
of car-oil change and •
temperature?
• Hypothesis? Increasing
temperature decreases the
time of car-oil change and
temperature?

5. • Define measurement scales:
– Temp: degrees centigrade
– Time in minutes
• Collect data
• Test hypothesis 70
60
Temperature (oC)
50
• Conclusion: 40
-increasing temp form 0-25 30
oC decreases time 20
10
-while increase above 25 oC 0
increases the time 0 10 20 30
Time (min)
40 50

6. Scientific research
• Systematic investigation of hypothetical
propositions about the presumed relations
among observed phenomena.

7. Clinical research
• Scientific research
• On
– humans or
– materials or
– data of human origin

8. Clinical research
• Is there a relationship
between Eczema and
number of car-oil change
in workers?
• Number of car-oil change
in workers
– Limits: 16/day
• Eczema
– Limits: non-invasive
(inspection and not biopsy)
– Eczema score: area in CM x
severity (0, 1, 2 3)

9. Clinical and preclinical research

10. Clinical and preclinical research
• Preclinical Research:
Ø Not in humans
Ø But will serve humans
Ø LAB
Ø Animal

11. Why we do research?
– To gain knowledge
• treat, prevent, diagnose diseases
• Human welfare
• Current and future patients
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12. Contributions to knowledge
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13. Why subjects engage in research?
– To help their diseases
– To help other patients
– Other benefits:
• e.g. payment
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14. Is research beneficial to patients?
• WE DO NOT KNOW:
– It could be beneficial
(Hopefully)
– It could prove harmful
– It could prove of no
benefit
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15. Research vs. routine practice
• Practice:
– Standard
– approved
– benefit
• Research: may not always benefit:
– Non-standard
– Non-approved
– Benefit?
• May receive highest care
• May directly benefit
• May be harmed
• Research gives Knowledge for better health
• Individual: respect, safety and dignity
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16. Study designs in health research
• Observational:
– No intervention
• Experimental:
– Intervention and outcome
• Semi-experimental
• True-Experimental
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17. Study designs in Clinical Research
• Observational:
– Research
– Not clinical trials
• Experimental:
– Research
– As well as clinical trials
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18. Observational studies
• Cross-sectional
• Case-control
• Cohort
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19. Cross-sectional studies
• Example:
– Obesity and Skin cancer
•.
Total SKIN cancer
Obese 350 (70%)
Non-Obese 150 (30%)
Total 500 (100%)
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20. Case-control studies
• Example:
– Lung cancer and smoking in Gharbia
Lung cancer No-lung cancer
Smoking 450 (90%) 150 (30%)
No-smoking 50 (10%) 350 (70%)
Total 500 500
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21. Cohort studies ‫ﺟﻤﺎﻋﺔ‬
• Example:
– Skin cancer following chest wall irradiation for
Breast cancer
Breast CA+RT Breast CA- RT
Skin cancer 10 (10%) 4 (1.3%)
No-SKIN cancer 90 (90%) 296 (98.7%)
Total 100 300
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22. Experimental Research
Interventional Research
• Phase I
• Phase II
• Phase III:
– Randomized controlled trial (RCT)
• Phase IV
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23. Experimental Research
Interventional Research
• Phase I • Semi experimental
• Phase II • Semi experimental
• Phase III: • True experimental
– Randomized controlled
trial (RCT)
• Phase IV
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24. Example of clinical trials
• Use of Nigella Sativa oil in treatment of
metastatic malignant melanoma
• ‫اﺳﺗﺧدام زﯾت ﺣﺑﺔ اﻟﺑرﻛﺔ ﻓﻲ ﻋﻼج ﺳرطﺎن اﻟﺟﻠد اﻟﺻﺑﻐﻲ اﻟﻣﻧﺗﺷر‬

25. Question?
• Why not going ahead and using this in all
patients ? ~ 100, 000

26. Steps
• Preclinical R
– Lab: manufacturing and
purification, solubility and preservation
– Cell lines
• Effective or not
– Animals
• Safe or not?
– Dose and frequency and duration AND Route
• Efficacious or not?
• Clinical R
– Safe or not? à phase I
– Efficacious or not? à phase II
– More effective than current
chemotherapy? à phase III
• What is next?

27. Phases of clinical trials

28. Why we use trials?
• Animal and human trials
• Predictability of safety and efficacy
• Animals:
– Safety prediction
– Diseases are different in animals: X efficacy
• Humans:
– Safety and efficacy prediction
• Prediction is never perfect
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29. Drug development cycle

30. Ethics in research

31. Preclinical Lab research
• New viruses
• New war weapons
• Resistant microbes

32. Pre-clinical animal research
• How long will guinea pig
live in atmospheric
temperature below 0°?
• How long will a guinea
pig live without food or
water?
• Carcinogenicity of car-
oil on guinea pig skin?

33. Clinical research
• How long will a human live in
atmospheric temperature
below 0°?
• How long will a human live
under a collapsed house
without food or water?
• This will decide the time
rescuers will spend on
searching?
• Carcinogenicity of car-oil on
human skin?

34. Clinical research
• Are these trials
acceptable?
• Is this clinical research
practice bad or good ?
• BCRP
• GCRP= GCP

35. Good Clinical Practice (GCP)
• By GCP we mean:
– Set of standards for clinical research
– From design àconduct à monitoring/auditing
à recording à analysis à reporting
• Aspects of GCP
– Science
– Ethics
– Quality

36. GCP
1 Value (science), ،‫اﻟﻘﯾﻣﺔ‬
2 Validity (quality), ‫ﺻﻼﺣﯾﺔ‬
3 Fairness (justice), ‫اﻟﻌداﻟﺔ‬
4 Risk– benefit ratio ‫ﻧﺳﺑﺔ اﻟﻣﺧﺎطر واﻟﻣﻧﺎﻓﻊ‬
(beneficence), (‫)اﻟﻣﻧﻔﻌﺔ‬
5 Protocol and its ‫اﻟﺑروﺗوﻛول‬
Independent review, ‫اﻟﻣراﺟﻌﺔ اﻟﻣﺳﺗﻘﻠﺔ‬
6 Consent, ‫اﻟﻣواﻓﻘﺔ اﻟﻣﺳﺗﻧﯾرة‬
7 Respect ‫اﻻﺣﺗرام‬
(Emanuel et al. 2000)
Belmont report, 1979.

37. GCP rules
• Social and scientific Value:
– respond to health needs and
– provide a sound question whose answers will advance
knowledge for the good of science and society.
• Validity (Quality):
– data generated from CR should be valid and interpretable
through proper design, endpoints and methodology.
• Fair subject selection:
– being non-biased and based of scientific grounds.
• Favorable risk– benefit ratio:
– through minimization of vulnerability and risk as well as
maximization of benefits.

38. • Independent review:
– to ensure adherence to the ethical guidelines in design, conduct
and analysis.
• Informed consent:
– the process that provides adequate information allows only
voluntary participation.
– Consent withdrawal should be allowed anytime in the research.
– Consent does not deprive subjects from any of their rights nor
does it alleviate researchers from their responsibilities in
protecting safety, rights and welfare of subjects.
• Respect for the enrolled subject’s:
– autonomy, right and welfare both during and after research.
– Individual’s rights and welfare should precede that of science
and society

39. BCP (Bad Clinical Practice)
• Does skin exposure to car-
oil leads to skin cancer?
• Orphan house
• Deal with manager
• Paint their skin with car-oil
daily for 8 hours then wash
• Do regular punch biopsied
of the skin each month
• Follow them without
treatment for the rest of
their lives

40. Good or bad
Point Fulfill Bad Good
ment
Value √ Skin cancer following Skin cancer following
exposure to car-oil exposure to car-oil
Validity (design) X Artificial exposure Spontaneous natural
exposure
Fair X Orphan house Oil station workers
risk– benefit ratio X No Tx allowed Tx allowed
Independent review X No Yes
Consent X No Yes
Kids Adults
Respect X Withdrawal not allowed Withdrawal allowed

41. Historical background of GCP
460 BC Oath of Hippocrates
1930's U.S. Food, Drugs and Cosmetic Act
1947 Nuremberg Code (following Nazi experiments in WWII)
1948 Declaration of Human Rights
1964 Declaration of Helsinki
1979 The Belmont Report
1982 International Guidelines for Biomedical
Research Involving Human Subjects
1996 ICH-GCP guidelines issued
1997 ICH-GCP guidelines becomes law in some countries

42. Goals of GCP
• To protect the rights, safety and welfare of
humans participating in research
• To assure the quality, reliability and integrity
of data collected
• To provide standards and guidelines for the
conduct of clinical research

43. The 13 principles of ICH-GCP
• Ethics:
1. Ethical conduct of clinical trials
2. Benefits justify risks
3. Rights, safety, and well-being of subjects prevail
• Protocol and science:
4. Nonclinical and clinical information supports the
trial
5. Compliance with a scientifically sound, detailed
protocol

44. The 13 principles of ICH-GCP
• Responsibilities:
6. IRB/IEC approval prior to initiation
7. Medical care/decisions by qualified physician
8. Each individual is qualified (education, training,
experience) to perform his/her tasks
• Informed Consent:
9. Freely given from every subject prior to
participation

45. The 13 principles of ICH-GCP
• Data quality and integrity:
10. Accurate reporting, interpretation, and
verification
11. Protects confidentiality of records
12. Investigational Products Conform to GMP’s and
used per protocol
• Quality Control/Quality Assurance
13. Systems with procedures to ensure quality of
every aspect of the trial

46. Parties involved in research

47. Parties involved in research
• Investigator
• Subject
• Sponsor
• CRO
• Ethics
committee
• Regulatory
authorities

48. Summary
• Scientific research
• Clinical research
• Clinical trials
– Phase I, II, III and IV
• Ethics in research
• GCP: standards or guidelines to ensure research is
scientific, ethical and of good quality
• Parties involved in research and their role and
responsibilities

49. Thank You
Ahmed A Zeeneldin
Director of Research Center (RCENCI)
Tel: 01111 000 943
Email: azeeneldin@gmail.com
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