Day One of Course

1. In the name of ALLAH, the most Gracious and the
most Merciful
Clinical Trials
Rising Regulations & Complexities
PBRS 2015
Obaid Ali, Roohi B. Obaid
April 5, 2015 :Group A & April 11, 2015 for Group B

2. Day 1
PBRS 2015
Obaid Ali, Roohi B. Obaid
Clinical Trials
Rising Regulations & Complexities

3. If you can’t explain it
Simply
You don’t understand
it well enough
Clinical Trials
Rising Regulations & Complexities

4. Clinical Trials
Rising Regulations & Complexities
The views expressed in this
presentation are not necessarily
of the DRAP.
It is an informal communication
that represents the best current
judgment and does not constitute
an advisory opinion or binding or
otherwise obligate or commit the
DRAP, to the views expressed.
This presentation is designed by
the speaker after consulting
international reference
documents
Disclaimer

5. Today’s Program

6. Today’s Program

7. Tutorial Focus

8. Tutorial Focus

10. Regulatory Authority Purview

11. From Silence to Reaction & Reaction to Proactive Role

12. See in the Back Mirror

13. See in the Back Mirror

14. See in the Back Mirror

15. See in the Back Mirror

16. See in the Back Mirror

17. See in the Back Mirror

18. See in the Back Mirror

19. Take off of 21st
Century

20. Who drives Safety Decision?

21. Human Subject Protection
A shared responsibility

22. Company Responsibility

23. Thalidomide Tragedy

24. Thalidomide Tragedy

25. Thalidomide Tragedy Loopholes

26. Incidence well Responded

27. Regulation in Action

28. Discuss during Tea

29. Tutorial Focus

30. Approvals are risk-benefit decisions

31. 3 Boundaries of Clinical Investigators

32. Regulations are designed & aimed to
ensure that

33. Clinical Investigators

34. Clinical Trial & Safety

35. From Journey of Brain to Hypothesis

36. Transformation from Hypothesis to
Concept Paper

37. Transformation from Hypothesis to
Concept Paper

38. From Concept Paper to Roadmap

39. Journey of Proof of Evidence

40. From Test Tube to Animal Studies

41. Pre-commitment attempt to make proof
undeniable

42. Data Integrity
Can anyone expect data that is error
free and practically verifiable
Very frankly
It is highly uncommon in academia
and research

43. ALCOA

44. Protection & well being of Human subjects
in Clinical Trial

45. Design to capture Considerable Facts
Unbiased
The study design should be robust enough to extract
maximum output and capable to uncover hidden facts

46. From Personalized to Generalized
Clinical Trial

47. Regulatory Assessment for Approval of
Clinical Trial

48. Representation of Actual Data

49. Representation of Actual Data

50. Surveillance & Post marketing Commitment
Discussion

51. Post marketing Requirement
Discussion

52. Development of Product Safety Data Sheet
Discussion

53. Trending & Pharmaco-metrics Evaluation
Discussion

54. Tutorial Focus

55. Study data unreliable and not used
Ketek
Marketing
Application
contains large
safety study
>1000 clinical
investigators
Routine data
audit
inspections
revealed
significant
noncompliance

56. Study data unreliable and not used
Investigator Fate

57. Area of Concern and Cases
Was the actual dose administered equal in strength to the intended dose?

58. Area of Concern and Cases
Was the actual dose administered equal in strength to the intended dose?

59. Area of Concern and Cases

60. Area of Concern and Cases
Reports of test article plasma concentrations in
untreated animals Concentrations measured in plasma
greatly exceed the LLOQ for the assay
Source

61. Area of Concern and Cases

62. Area of Concern and Cases

63. Area of Concern and Cases

64. Area of Concern and Cases

65. Area of Concern and Cases

66. Area of Concern and Cases

67. Area of Concern and Cases

68. Step by Step Action in Normal Situation

69. Retard History Continued-Holland Case
Study coordinator enrolled ineligible subjects in oncology trials
Coordinator altered source records and created fraudulent CRFs to
make subjects appear eligible
Data manipulations should have been apparent to attentive clinician
Subject who was ineligible due to poor renal and liver function was
enrolled, dosed, and died as a result
Study coordinator sentence to 71 months in prison and debarred from
many future involvement in FDA regulated research
Dr. Holland – 5 years probation, $500k restitution to defrauded drug
companies, disqualified

70. Retard History Continued
Palazoo Case
Paxil trial
(87 months imprisonment)

71. Homework
Read cases as given
individually
Write 1 page handwritten
summary report
Make 5 slides to present your
understanding
Conduct interview and
compile answers for e.g.
Would you allow your loved one of 2 month age for Phase 1 clinical
trial at AKUH? If not, what’s the reason?

72. If you can’t explain it
Simply
You don’t understand
it well enough
Clinical Trials
Rising Regulations & Complexities

73. Thank you
See you in next session
InshaAllah
Clinical Trials
Rising Regulations & Complexities