251008-CQS Learning-Professional Development-PVDS.pdf

Certificate Course by Centre for Quality Sciences, Karachi for selected professionals

1. From validated methods to real evidence …. Centre for Quality Sciences…. Where insight and integrity matters
Wednesday
08 October 2025
09.30 to 3.30 pm
At Hotel Marriott
Karachi
CQS Learning
Pharmacovigilance
& Drug Safety
1
st
Session of Professional
Development Exercise for
limited Professionals

3. CQS Learning
Pharmacovigilance & Drug Safety
08 Oct 2025 –Hotel Marriott, Karachi
Gathering: 09.30 am
Opening & Introduction:SQ 09.45 to 10.00 am
Overview of the Program: RO 10.00 to 10.30 am
A Back Mirror Review: RO 10.30 to 11.15 am
Tea Break: --- 11.15 to 11.45 am
Current Historical Moves: OA 11.45 to 12.30 pm
Discussion & Exercise:OA 12.30 to 01.15 pm
Lunch & NamazBreak: --- 01.15 to 02.15 pm
Experience based Learning:RO 02.15 to 02.30 pm
Q& A: OA 02.30 to 03.30 pm
Closing: 03.30 pm

4. Overview of the Program

5. Tutorial
Discussions
Case Studies
Group Discussions
Individual Homework
Dr. AjazS. Hussain
Dr. ObaidAli
RoohiB. Obaid

6. Pharmacoepidemiology

7. Pharmacoepidemiology
Study of the use and effects of
drugs in large populations
It combines pharmacology and
epidemiology

8. Pharmacoepidemiology
Key Features
•Drug Utilization
•Safety
•Efficacy
•Comparisons
•Policy Impact

9. Pharmacoepidemiology
Example Questions
•Does long term use of
omeprazole increase the
risk of kidney disease in
general population?
•Is acetaminophen use
during pregnancy linked to
autism in children?

10. Pharmacoepidemiology
Methods:
•Observational studies: cohort,
case-control, cross-sectional
•Database Research: analyzing
prescriptions, hospital records
•Signal detection: using
pharmacovigilance systems
•Clinical trial follow ups in real
world settings

11. Pharmacoepidemiology
What are the challenges in
way of ensuring drug safety?
What do you think are we
losing public trust or gaining
public trust?
How much it is complex?
Please share your views

12. Pharmacoepidemiology
What are the challenges in
way of ensuring drug safety?
What do you think are we
losing public trust or gaining
public trust?
How much it is complex?
Please share your views

13. Pharmacoepidemiology
What are the challenges in
way of ensuring drug safety?
What do you think are we
losing public trust or gaining
public trust?
How much it is complex?
Please share your views

14. What is effective &
What is safe?

15. What is effective &
What is safe?
What is quality & what is high
quality?
What are the benefits & what
are the risks?
How we calculate it? How
Regulatory Authority calculate
it?

16. What is effective &
What is safe?
What is quality & what is high
quality?
What are the benefits & what
are the risks?
How we calculate it? How
Regulatory Authority calculate
it?

17. What is effective &
What is safe?
What is quality & what is high
quality?
What are the benefits & what
are the risks?
How we calculate it? How
Regulatory Authority calculate
it?

18. What is ADE
Adverse Drug Event
How ADE is detected?
How it is monitored?
What are the legal
frameworks?

19. What is ADE
Adverse Drug Event
How ADE is detected?
How it is monitored?
What are the legal
frameworks?

20. What is ADE
Adverse Drug Event
How ADE is detected?
How it is monitored?
What are the legal
frameworks?

21. What is ADE
Adverse Drug Event
How ADE is detected?
How it is monitored?
What are the legal
frameworks?

22. History of
Pharmacovigilance
Pharmacoepidemiology&
Health Economics

23. CQS time
commitment
30 hours formal teaching &
one to one contact
50 hours self directed study
50 hours for projects

24. CQS time
commitment
30 hours formal teaching
& one to one contact
50 hours self directed
study
50 hours for projects

25. CQS time
commitment
30 hours formal teaching
& one to one contact
50 hours self directed
study
50 hours for projects

26. CQS time
commitment
30 hours formal teaching
& one to one contact
50 hours self directed
study
50 hours for projects

27. Assessment
3000 to 5000 words
written project
2 hour exam
15 min presentation

28. Assessment
3000 to 5000 words
written project
2 hour exam
15 min presentation

29. Assessment
3000 to 5000 words
written project
2 hour exam
15 min presentation

30. Assessment
3000 to 5000 words
written project
2 hour exam
15 min presentation

31. A Back Mirror Review

32. From 19 & 20
th
Century
Small Pox Vaccine
Tetanus Toxoid
And many more
No vigilance and if so it
was meaningless

33. 1937
What happened?

34. 1962
What happened?

35. 2011
What happened?

36. 2018
What happened?

37. 2025
What happened?

38. Challenges
Chronic diseases
Everything is growing except
health
Half a million dollar gene
therapy
Cancer, Diabetes,
Cardiovascular, Allergies,
Asthma, Autism
About 10 billion doses of
analgesic in Pakistan/year

39. Current Historical Moves

41. Just imagine &
share the name
of drug ….
That you consider safe or
relatively safe ….
With residual risk

42. Why?
What are the blind
spots?
What are the unknowns?
What may go wrong?

43. SurveillanceVigilance

44. Studies
•Publication
•Sample Size
•Exposure
•Association
•Causal Approach

45. JAMA 2024
2.48 Msingletons (1995 to 2019).
Exposure: Registry/dispensation.
Population: Small increased
ASD/ADHD risk.
Causal Probe:Sibling (within
family) comparisons, associations
attenuated to null.
Interpretation: Familial
confounding likely.

46. JAMA Psychiatry
2020 (Boston Birth)
N= 996 mother infant dyads.
Exposure: Cord plasma
acetaminophen metabolites.
Finding:
Higher biomarkers
Higher ASD/ADHD odds
(tertiledose response).
Causal Probe:Covariate adjusted
models; biomarker reduces
misclassification but residual
confounding remains.

47. Am J Epidemiol
2019
N= 8,856 children; 721 ADHD
cases.
Exposure: Prospective maternal
self report.
Finding: Regular prenatal use
associated with ADHD.
Causal Probe:Negative-control
exposure analyses (pre/post
pregnancy comparisons),
strengthens pregnancy specific
signal but not definitive.

48. Autism Res 2016
(Danish DNBC)
N≈64,322 children.
Exposure: Prospective maternal
report; duration assessed.
Finding: Longer duration linked to
increased ASD risk for some
phenotypes.
Causal Probe:Dose response
analyses; confounding and
indication bias possible

49. MoBaCohort
Analyses
(Norway)
Analytic Ns vary; cohorts
~112,000 children.
Exposure: Prospective self report.
Finding: Prolonged use (weeks)
associated with higher ADHD risk.
Causal Probe:Adjusted
regression; some sibling analyses
attenuate effects.

50. JAMA Pediatrics /
Meconium + MRI
(2020)
N= 345 with meconium data; 199
positive for acetaminophen.
Exposure: Meconium (cumulative
fetal exposure).
Finding:
Acetaminophen detected
Higher ADHD odds
Brain connectivity
differences partially
mediated effect.
Causal Probe:Biomarker &
mediation improves plausibility;
sample small.

51. Key Points
•Knowns
•Unknowns
•Strengths
•Weaknesses

52. Known
Repeated Associations
Multiple cohorts show
population level positive
associations between prenatal
acetaminophen and
ADHD/ASD in offspring.

53. Known
Exposure Measurement
Matters
Biomarkers (cord plasma,
meconium) reduce
misclassification and often
show stronger signals versus
self report.

54. Known
Dose Duration Pattern
Several studies report larger
risk with longer duration or
higher cumulative exposure.

55. Unknown
Causality
No randomized trials. Sibling
comparison analyses (largest
study) nullify associations,
suggesting confounding.

56. Strong Evidence
•Large registry data (power)
•Biomarker confirmation
•Dose response signals
•Negative control analyses
•Each strengthens inference
in different ways

57. Weaknesses
•Residual confounding
•Indication bias
(fever/infection)
•Exposure timing/dose
uncertainty (Self Report)
•Limited mechanistic human
data

58. Balanced
Interpretation
•Association repeatedly
observed but inconsistent
under stronger causal
designs
•Evidence is concerning yet
inconclusive

59. Pakistan
Questions &
Recommendations

60. Q-1
Signal or
Confounder
Are observed Associations
due to acetaminophen itself,
maternal illness, genetics, or
shared environment?

61. Q-2
Exposure
Quantification
Can Pakistan implement
biomarker sampling (cord
blood, meconium) to improve
exposure specificity?

62. Q-3
Dose & Timing
What thresholds
(dose/duration/gestational
window) if any, increase risk
meaningfully?

63. Q-4
Mechanism
Is there reproducible human
mechanistic evidence
(inflammation, oxidative
stress, neurotransmitter
changes)?

64. Let’s see what can be done

65. National Sentinel
Surveillance
•Establish maternity
hospitals to collect
standardized maternal
exposure data
•Neonatal cord blood,
meconium, and follow up
neurodevelopmental
outcomes

66. Strengthen
Pharmacovigilance
•Add pregnancy exposure
reporting to national PV
system
•Enable rapid linkage of
mother child records

67. Strengthen
Pharmacovigilance
•Add pregnancy exposure
reporting to national PV
system
•Enable rapid linkage of
mother child records

68. Biomarker Pliot
Program
A multi-site pilot (cord
plasma & meconium) with
N≥1,500 to provide Pakistan
specific exposure outcome
data

69. Registry Linkage
& Sibling Analyses
Create mother child registries
enabling within family
(sibling) analyses to control
familial confounding

70. Clinical Guidance
Advise Clinicians
•Use acetaminophen in
pregnancy only when necessary
•Lowest effective dose
•Shortest duration
•Emphasize fever control when
indicated

71. Reserach Priorities
•Support Mechanistic Studies
•Larger Biomarker Cohorts
•Data sharing with international
consortia for meta-analyses

72. Communication
Strategy
Public Messaging
Honest & non alarming
Occasional short-term use
reasonable
Avoid prolonged or frequent use
without medical advice.

73. Minimum
DataSet for Pilots
•Mother ID & Sibling IDs
•Gestational age
•Indication (fever/pain)
•Dose/duration
•Cord plasma acetaminophen
•Meconium assay
•Neurodevelopmental screening
at 12/24/36 months

74. Cost Benefit Note
Pilot biomarker program &
Registries are moderate cost
with high policy value
Enable evidence based
guidance and targeted risk
mitigation.

75. Conclusion
Evidence: repeated
associations but no definitive
causality.
Pakistan should rapidly build
real time exposure
surveillance plus biomarker
studies to inform safe,
contextual public health
policy.

76. Discussion & Exercise

77. Experience based Learning

78. Experience based
Learning
•# of years on the job is not
real experience
•Experience is practical
contact with events …
Experience is to feel
(emotions)
•It comes through reflection
on doing

79. Experience based
Learning
Your emotionsshapes your
thinking …..
Your emotions are your
feelings….. that designyour
attention …..

80. Experience based
Learning
Experience is in between
information& knowledge
Feelthe information in
practice, it becomes
knowledge

81. Experience based
Learning
Between Knowledge &
Wisdom there are two
processes
•Understanding
•Sense making

82. Experience based
Learning
21
st
Century is the experience
economy
Real world experience in the
market where …
Patient experience
Therapeutic outcome
… is more fundamental today than
ever before

84. Viktor E. Frankl
Between stimulus and
response there is a space. In
that space lies our power to
choose our response. In our
response lies our growth and
our freedom

85. Jalal ad-Din
Mohamamad Rumi
Always remember you are
braver than you believe,
stronger than you seem,
smarter than you think, and
twice as beautiful as you'd
ever imagined.
Yesterday I was clever, so I
wanted to change the world.
Today I am wise, so I am
changing myself.

86. Thanks