Definitions and Importance of PV.ppt11111111111122222222222

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1. 1
WORKING FOR YOUR SAFETY
Definitions and
Importance of
Pharmacovigilance
MODULE I

2. Overview
•Definitions in Pharmacovigilance (PV)
•History, Purpose and Scope of PV
•Burden of Adverse Drug Reactions
•Clinical Trials and Limitations of Clinical Trials
•Spontaneous Reporting
–Strengths and limitations
•Other methods of post approval safety
monitoring of drugs and vaccines
•Summary
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3. Definitions in Pharmacovigilance
3

4. Pharmacovigilance (PV)
•Pharmakon: drug
•Vigilare: to keep awake or alert; to keep
watch
(Viewpoint Part 1, UMC)

5. •The science and activities relating
to the detection, assessment,
understanding and preventionof
adverse effects or any other drug-
related problems.
(WHO, 2002)
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6. Vaccinovigilance (Vaccine PV)
•The science and activities relating to the
detection, assessment, understandingand
communicationof AEFI and other vaccine-
or immunization-related issues, and to the
prevention of untoward effects of the
vaccine or immunization.
(CIOMS/WHO Working Group 2012)

7. Pharmacovigilance & Vaccine Pharmacovigilance
Pharmacovigilance
Any untoward medical
occurrence that at any dose:
Vaccine
Pharmacovigilance
Science and activities
relating to the
detection, assessment,
understanding
and prevention of
adverse effects or any
other drug-related
problems.
Vaccine pharmacovigilance* the
science and activities relating to
the detection, assessment,
understanding and communication
of AEFI and other vaccine-or
immunization-related issues, and
to the prevention of untoward
effects of the vaccine or
immunization.
* Report of CIOMS/WHO Working Group on Vaccine Pharmacovigilance, 2012

8. History, Purpose and Scope
of Pharmacovigilance

9. History
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•1960: Thalidomide
̶Foetal abnormalities related to the use of Thalidomide-
marketed as mild sleeping pill and remedy for morning
sickness during pregnancy
•1962: US Food and Drugs Administration
̶revised law requiring the proof of safety in addition to
quality and efficacy before issuing marketing
authorisation (Kefauver-Harris Amendment)
•1964: UK starts “yellow cards” system
•1968: Global
̶WHO Collaborating Centre for International Drug
Monitoring (Uppsala Monitoring Centre or UMC); fully
functional in 1978.
•2001: PV in Ghana, 65
th
member of the UMC and 1
st
country
in W. Africa to join the programme

10. Thalidomide -Phocomelia

11. Purpose of Pharmacovigilance
•To identify previously unrecognized adverse drug
reactions or changes in the patterns of adverse
drug reactions
•To assess risks and benefits of medicines/vaccines in
order to determine what action, if any, is necessary
to improve patient safety
•To provide information to healthcare professionals,
patients and other stakeholders to optimize safe
and effective use of medicines/vaccines
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12. The ultimate purpose
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•To reduce risks associated with
marketed drugs and vaccines
•To improve patient safety
Purpose of Pharmacovigilance

13. •Irrational drug use
•Drug abuse
•Medication errors
•Traditional and
herbal medicines
•Lack of efficacy
•Substandard and
counterfeit
medicines
•Blood and Blood
products
•Cosmetics
•Medical devices
The Scope of Pharmacovigilance
The scope of PV has broaden to include:

14. PV Activities
Adopted from: R. Edwards. British Journal of Clinical Pharmacology 73(6)·June 2012

15. Aresponsetoamedicinalproductwhich is
noxiousandunintendedincludinglackofefficacy
and whichoccursatanydosage and can arise from:
•The use of product within the terms of the marketing
authorization;
•The use of product outside the terms of the marketing
authorization, including overdose, off-label use,
misuse, abuse and medication errors;
•Occupational exposure
AdverseDrugReactionor AdverseReaction
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16. Adverse Events Following Immunization (AEFI):
Symptom
Sign
Lab Finding
Disease
…any untoward
medical occurrence
which follows
immunization and
which does not
necessarily have a
causal relationshipwith
the usage of the
vaccine.
The adverse event
may be any
unfavorable or
unintended sign,
abnormal laboratory
finding, symptom or
disease.

17. 1
Vaccine
product-
related
reaction
An AEFI that is
caused or
precipitated by
a vaccine due
to one or more
of the inherent
properties of
the vaccine
product.
2
Vaccine quality
defect-related
reaction
An AEFI that is
caused or
precipitated by
a vaccine that
is due to one
or more
quality defects
of the vaccine
product
including its
administration
device as
provided by
the
manufacturer.
3
Immunization
error-related
reaction
An AEFI that is
caused by
Inappropriate
vaccine
handling,
prescribing or
administration.
4
Immunization
anxiety-related
reaction
An AEFI arising
from anxiety
about the
immunization.
5
Coincidental
event
An AEFI that is
caused by
something
other than the
vaccine
product,
immunization
error or
immunization
anxiety
CIOMS/ WHO cause specific definition of AEFIs

18. WORKING FOR YOUR SAFETY 18
Serious ADR/AEFI
•Noxious and unintended response to a
drug/vaccine, which results in any of the
following:
–Death
–Hospitalization/prolongation of hospitalization
–Congenitalanomaly/birthdefect
–Persistent or significant disability or incapacity
–a life-threatening condition
***‘Serious’ is notsynonymous with ‘severe’ (i.e., intensity or
severity of the event)

19. Side effect
•Any unintended effect of a
pharmaceutical product occurring at
normal dosage which is related to the
pharmacological properties of the drug.
•Harmful or beneficial
•Aspirin-Gastro intestinal bleeding
•Cyproheptadine-weight gain, increased
appetite

20. Medication Errors
•Any preventable event that may
cause or lead to an inappropriate
medication use or patient harm
while in the control of the health
care professional, patient or
consumer’’.
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21. Medication Errors
•An unintended failure in the drug treatment
process that leads to, or has the potential to
harm a patient.
•This include;
•The prescribing, storing, dispensing,
preparation for administration or
administration of a medicinal product

22. Examples of medication errors
•Giving a medication to a patient for whom it
was not intended
•Giving the wrong medication to a patient
•Giving the wrong dose/dose regimen of a
medication to a patient
•Forgetting to give patient a medication that
had been prescribed for them

23. Common causes
•Similar sounding names
•Similar looking labelling
•Similar medicinal containers

24. WORKING FOR YOUR SAFETY 24Similar Sounding and look alike names

25. Similar-looking labeling

26. SSFFCs
•Substandard-Medicines that are outside of specification,
excludes genuine manufacturing but may include intentional,
reckless or negligent errors.
•Spurious-Terminology for products falsely labelled or
intended to deceive.
•Falsely labelled-Includes genuine product with false
packaging
•Falsified-Terminology to include a deliberate intention to
deceive.
•Counterfeit-Deliberate attempt to imitate a genuine
product
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27. Signal
•Reported information on a possible
causal relationship between an adverse
event and a drug, the relationship being
unknown or incompletely documented
previously.
–Usually more than a single report is required to
generate a signal, depending upon the seriousness
of the event and the quality of the information.
–The publication of a signal usually implies the need
for some kind of review or action.

28. Adverse Event
•Any untoward medical occurrence in
a patient or clinical trial subject
administered a medicinal product
and which does not necessarily have
a causal relationship with this
treatment

29. Dechallenge
•Dechallenge –withdrawing the
drug(s) and recording the outcome –
improved or not improved
–Positive dechallenge: a situation in
which an adverse event disappears
after the stopping of a drug

30. Dechallenge
–Negative dechallenge: this refers to a
situation where an adverse event does
not disappear after the stopping of a
drug.

31. Rechallenge
•Rechallenge –giving onedrug again
under the same conditions as before and
recording the outcome –recurrence or
no recurrence.
–Positive rechallenge: this refers to a situation
whereby an adverse event recurs after restarting a
drug
–Negative rechallenge: this is where an adverse
event does not recur after a drug is restarted

32. The burden of Adverse
Drug Reactions (ADRs)

33. The Burden of ADRs
•39 prospective studies from US
hospitals
̶Overall incidence of serious ADRs = 6.7%
̶Overall incidence of fatal ADRs = 0.32%
̶(106 000 individuals)
̶4th -6th leading cause of death
Lazarouet al JAMA 1998;279: 1200 -1205
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34. •6.5% of admissions are due to ADRs
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Cost £446 million per annum
The Burden of ADRs

35. The Burden of ADRs
•740 New Molecular Entities approved by the US FDA: 1980-2009
•118 (15.9%) were discontinued
–Pharmacoepidemiol Drug Saf.2011 Jul; 20(7):772-7
•Popular drugs withdrawn for safety reasons since 2000
–Troglitazone(Rezulin) : hepatotoxicity
–Levamisole(Ergamisol) : agranulocytosis
–Astemizole(Hismanal) : arrhythmias due to drug interactiuons
–Cisapride(Propulsid) : cardiac arrhythmias
–Cerivastatin(Baycol) : rhabdomyolysis
–Rofecoxib(Vioxx) : myocardial infarction
–Valdecoxib(Bextra) : heart attack and stroke
–Tegaserod(Zelnorm) : heart attack and stroke
–Sibutramine(Reductil) : cardiovascular risks
–Propoxyphene(Darvon) : heart attack and stroke
–Rosiglitazone(Avandia) : increased risk of heart attacks and death.
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36. 2015 Outcome of ADRs
DrugLens®, Issue 4, April 2016
The Burden of ADRs

37. The need for PV in Ghana

38. Why PV is needed in Ghana?
•Disease and prescribing practices
•Genetics, diet and traditions of the people
•Drug manufacturing processes which
influence pharmaceutical quality and
composition
•Drug distribution and use including
indications, dose and availability
•The use of traditional and complimentary
medicines

39. Limitations of pre marketing
clinical trials and importance of
Pharmacovigilance

40. Phase IV
Post-approval studies to
determine specific safety issues
Clinical development of medicines
Animal experiments for
acute toxicity, organ
damage, dose dependence,
metabolism, kinetics,
carcinogenicity,
mutagenicity/teratogenicity
Preclinical
Animal
Experiments
Phase I Phase II
Development Post Registration
Phase III
Phase IV
Post-approval
Spontaneous
Reporting
Registration
Phase I
20 –50 healthy volunteers
to gather preliminary data
Phase II
150 –350 subjects with
disease -to determine
safety and dosage
recommendations
Phase III
250 –4000 more varied
patient groups –to
determine short-term safety
and efficacy 40
Stages of Drug Development

41. Limitations of Clinical Trials Subject
RCT
(efficacy)
Clinical practice
(effectiveness)
 Number of patients
Dozens, hundreds, rarely
thousands
Thousands to millions
 Length of time Days to weeks Days to years
 Population
Pregnant, children, the
elderly are sometimes
excluded
Potentially, all the
population
 Other treatments They are avoided Possibly, more than one
 Conditions Ideal conditions Conditions vary

42. Spontaneous Reporting;
Strengths and Limitations

43. •Unsolicited communication from
–Healthcare professionals,
–Patients, and
–Consumers
of suspected ADRs
•Not from organized data
collection system where ADR
reporting is actively sought
•Stimulated Spontaneous reporting
Spontaneous reporting

44. •Strengths
–All products (drugs, vaccines, herbal
medicines, medical devices, etc) and
entire population
–Cheaper compared to other methods
–Helpful in the identification of signals
–Identification of adverse reactions with
very low frequency
Spontaneous reporting

45. •Limitations
–under-reporting
–variable quality of the reported data
–lack of information on exposure
–Bias
Spontaneous reporting

46. What to Report
•ADRs from:
–Over-the-counter, pharmacist initiated and
prescription medicines
–Medical devices , Food supplements, Cosmetics,
Household chemical substances
–Therapeutic ineffectiveness, drug abuse, drug
overdose, drug interactions, quality defects, poor
packaging, suspected contamination, suspected
counterfeit.
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Spontaneous reporting

47. Other Methods of Post
Approval Safety Monitoring

48. Other Methods
•Observational Studies
–Cohort Event Monitoring (CEM)
–Cohort studies
–Case-control Study
–Case-only Study
–Cross sectional Study
–Registries (disease, exposure, condition)
•Active Intervention Safety Surveillance
–Post-Authorization Safety Studies (PASS)

49. Summary
•Pharmacovigilance means to keep watch
over medicines
•The scope of pharmacovigilance has been
widened to include any other possible
drug/vaccine related problem
•Pharmacovigilance is needed in all
countries to protect patient safety
•Spontaneous reporting is the cornerstone of
pharmacovigilance
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50. Thank you