2- Introduction to Pharmacovigilance
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Transcript of 2- Introduction to Pharmacovigilance
Introduction to Pharmacovigilance 11 & 12 Dec 2011
Dr Amr Saad. Lecture - Head of the
Egyptian Pharmacovigilance Center 1
Introduction to
Pharmacovigilance
The Egyptian Pharmacovigilance
Center (EPVC)
Amr Saad PhD in Clinical Pharmacy and Pharmacoepidemiology
University of Manchester, UK Head of the Egyptian Pharmacovigilance Center
Outlines of the presentation
• Smooth orientation to Pharmacovigilance concept.
• Why do we need Pharmacovigilance?
• Important Terminologies in Pharmacovigilance
• Marketing the idea of Pharmacovigilance.
• Global vision of Pharmacovigilance.
Introduction to Pharmacovigilance 11 & 12 Dec 2011
Dr Amr Saad. Lecture - Head of the
Egyptian Pharmacovigilance Center 2
Smooth orientation to Pharmacovigilance concept
Medicines are safe! (X)
Approved medicines are safe! (X)
No medicine is safe! (X)
No medicine is without risk! (√)
Risk/Benefit Balance of medications
Introduction to Pharmacovigilance 11 & 12 Dec 2011
Dr Amr Saad. Lecture - Head of the
Egyptian Pharmacovigilance Center 3
Risk-benefit balance
Unacceptable
acceptable
Emerging safety consideration of
medications
Quality
Safety
Efficacy
Introduction to Pharmacovigilance 11 & 12 Dec 2011
Dr Amr Saad. Lecture - Head of the
Egyptian Pharmacovigilance Center 4
WHO definition of pharmacovigilance
• “Pharmacovigilance is the science and activities relating to
the detection, assessment, understanding and prevention of
adverse effects or any other medicine-related problem”
Learning from History
Thalidomide Disaster:
• Tranquilliser launched - 1957
• First reports of birth defects - 1959
• 13 reports of birth defects - 1961
• Withdrawn shortly afterward
• 10000 infants affected by Phocomelia.
• No teratogenicity detected in testis during clinical trials and prior
to launch.
Introduction to Pharmacovigilance 11 & 12 Dec 2011
Dr Amr Saad. Lecture - Head of the
Egyptian Pharmacovigilance Center 5
Phocomelia
Phocomelia cases – 15% Death rate
Introduction to Pharmacovigilance 11 & 12 Dec 2011
Dr Amr Saad. Lecture - Head of the
Egyptian Pharmacovigilance Center 6
Pharmaco - vigilance
• Pharmaco = medicine
• Vigilare = to watch
alert watchfulness
forbearance of sleep; wakefulness
watchfulness in respect of danger; care; caution
the process of paying close and continuous attention
WHO definition of pharmacovigilance
• “Pharmacovigilance is the science and activities relating to
the detection, assessment, understanding and prevention of
adverse effects or any other medicine-related problem”
Introduction to Pharmacovigilance 11 & 12 Dec 2011
Dr Amr Saad. Lecture - Head of the
Egyptian Pharmacovigilance Center 7
Pharmacovigilance in its broadest term
• Monitoring medicines to determine unrecognized ADRs or
changes in their patterns
* Spontaneous reporting, signals detection
• Continuously re-assessment the risk/benefit of medicines,
taking action if necessary to improve their safe use……
* adding information to the SPC (Inserts), restricting use of a
drug, withdrawing a drug.
Lifecycle of Pharmacovigilance Data
Data Collation & Review
Benefit/Risk
Evaluation
Signal Detection Risk Mgt.
Communication Drug Safety Monitoring
Introduction to Pharmacovigilance 11 & 12 Dec 2011
Dr Amr Saad. Lecture - Head of the
Egyptian Pharmacovigilance Center 8
Drug safety throughout product life cycle
Preclinical Clinical trial Market authorization Clinical practice
Clinical Drug Safety
Post Marketing Surveillance
Pharmacovigilance Pharmaco-epidemiology
Passive
Tools ► Spontaneous reports ► Literature searching
Tools ►PMS* studies
Active
Why do we need Pharmacovigilance?
Introduction to Pharmacovigilance 11 & 12 Dec 2011
Dr Amr Saad. Lecture - Head of the
Egyptian Pharmacovigilance Center 9
Clinical Development of Medicine
Animal studies (Pre-clinical phase)
• ADME*
• Acute toxicity
• Sub-acute, chronic toxicity
• Carcinogenicity
• Reproductive toxicity
• Mutagenicity
• Teratogenicity
Introduction to Pharmacovigilance 11 & 12 Dec 2011
Dr Amr Saad. Lecture - Head of the
Egyptian Pharmacovigilance Center 10
Clinical trial phases
Phase I
Phase II
Phase III
Nu
mb
er
of
pat
ien
ts
Development time
Clinical trial phases
Introduction to Pharmacovigilance 11 & 12 Dec 2011
Dr Amr Saad. Lecture - Head of the
Egyptian Pharmacovigilance Center 11
Frequency scale of adverse drug
reactions (ADRs)
Lag time for adverse drug reactions
(ADRs)
Introduction to Pharmacovigilance 11 & 12 Dec 2011
Dr Amr Saad. Lecture - Head of the
Egyptian Pharmacovigilance Center 12
Limitations of clinical trials
• Small number of patients studied
• Restricted populations (age, sex, ethnicity)
• Narrow indications
• Short duration of drug exposure
Important Terminologies in Pharmacovigilance
Introduction to Pharmacovigilance 11 & 12 Dec 2011
Dr Amr Saad. Lecture - Head of the
Egyptian Pharmacovigilance Center 13
Side Effect (SE) Vs Adverse Drug
Reaction (ADR) Vs Adverse Event (AE)
• SE Response to a drug which is unintended and which occurs at
doses normally used in man for prophylaxis, diagnosis or therapy
of disease or for modification of physiological function.
• ADR Response to a drug which is noxious and unintended and
which occurs at doses normally used in man for prophylaxis,
diagnosis or therapy of disease or for modification of physiological
function. A causal relationship between the drug and the
occurrence is suspect.
• AE Any untoward medical occurrence in a patient or clinical
investigation subject administered a medicinal product and which
does not necessarily have to have a causal relationship with this
treatment.
Adverse Drug Reaction (ADR) Vs
Adverse Event (AE)
Introduction to Pharmacovigilance 11 & 12 Dec 2011
Dr Amr Saad. Lecture - Head of the
Egyptian Pharmacovigilance Center 14
Medication Errors (ME)
• They could occur during prescribing, transcribing, dispensing,
administering a drug. Examples of medication errors include,
misreading or miswriting a prescription.
• Not all medication errors lead to adverse outcomes.
• Medication errors are more common than adverse events, but
result in harm less than 1% of the time. About 25% of adverse
events are due to medication errors.
* Nebbeker et al. Ann Intern Med. 2004; 140:795-801.
Adverse Drug Reactions (ADR) vs Adverse
Events (AE) vs Medication Errors (ME)
Introduction to Pharmacovigilance 11 & 12 Dec 2011
Dr Amr Saad. Lecture - Head of the
Egyptian Pharmacovigilance Center 15
ADR classification
• Type A reactions
Dose-related & Predictable from drug pharmacology
Common & Normally reversible
May be manageable with dose adjustment
Example: bleeding with warfarin
• Type B reactions
Not dose-related, Unpredictable & Uncommon
May be serious/irreversible
Indicative that drug needs to be stopped
Example: anaphylaxis with penicillin
ADR classification
• Type C reactions – Chronic
Repeated drug use
• Type D reactions – Delayed
Take time to develop
Carinogenesis, teratogenesis
• Type E reactions - End of treatment
Withdrawal, rebound phenomena etc.
• Type F – Failure
Treatment did not work – therapeutic failure
Vaccines, OCPs
Introduction to Pharmacovigilance 11 & 12 Dec 2011
Dr Amr Saad. Lecture - Head of the
Egyptian Pharmacovigilance Center 16
Cascade down of Medicine information
Unlisted Adverse Reaction
• An ADR that is not specifically included as a suspected adverse
effect in the Company Core Safety Information (CCSI). This
includes an adverse reaction whose nature, severity, specificity, or
outcome is not consistent with the CCSI.
• It also includes class-related reactions which are mentioned in the
CCSI but which are described as occurring with this product.
Introduction to Pharmacovigilance 11 & 12 Dec 2011
Dr Amr Saad. Lecture - Head of the
Egyptian Pharmacovigilance Center 17
Unexpected Adverse Reaction
• An ADR whose nature, severity, specificity, or outcome is not
consistent with the Summary of Product Characteristics (SPC).
• It includes class-related reactions which are mentioned in the SPC
but which are not specifically described as occurring with this
product.
Serious Adverse Event (SAE)
• Any untoward medical occurrence that at any dose:
results in death,
is life-threatening,
requires inpatient hospitalization or results in prolongation of
existing hospitalization,
results in persistent or significant disability/incapacity,
is a congenital anomaly/birth defect,
is a medically important event or reaction.
Introduction to Pharmacovigilance 11 & 12 Dec 2011
Dr Amr Saad. Lecture - Head of the
Egyptian Pharmacovigilance Center 18
Marketing for the idea of Pharmacovigilance
Marketing for the idea of
Pharmacovigilance
►Part of the practice
►Humanitarian & Ethical concerns
►Economical concern
Introduction to Pharmacovigilance 11 & 12 Dec 2011
Dr Amr Saad. Lecture - Head of the
Egyptian Pharmacovigilance Center 19
Part of the practice
Health Care Professionals (HCPs).
Manufacturers and Marketing Authorization Holders (MAH).
Regulatory Authorities (RA).
Civil societies and Medical and pharmaceutical syndicates
Ethical concerns
►Humanitarian concerns: Hippocratic oath “First
Do No Harm”
• To know of something that is harmful to
another person, who does not know, and not
telling, is unethical
• Valid for:
Patient
Health professional
Manufacturer
Authorities
Introduction to Pharmacovigilance 11 & 12 Dec 2011
Dr Amr Saad. Lecture - Head of the
Egyptian Pharmacovigilance Center 20
►Check if drugs on the market fulfill their intended role in society
• Check if resources spent on drugs produce optimal results in terms
of:
alleviating human suffering
reducing disease related economical loss
Economical concerns
Economical concerns
ADVERSE EFFECTS
Medication Errors
Preventable ARs
Unpreventable ARs
Quality Problems
US study 1994
4th – 6th cause of death
5% hospital admissions
Occur in 11% patients
Double cost/length of stay
Double mortality rate
Less than 1% reported
Introduction to Pharmacovigilance 11 & 12 Dec 2011
Dr Amr Saad. Lecture - Head of the
Egyptian Pharmacovigilance Center 21
High burden
• Lazarou et al JAMA 1998; 279:1200-1205
Meta-analysis of 39 prospective studies from US hospitals
Incidence of hospital admissions due to serious ADRs = 6.7%
Fatality rate = 0.32% (106 000 individuals)
4th - 6th leading cause of death
• Pirmohamed M. et al. Br Med J 329:15-19 (2004)
Incidence of UK hospital admissions due to serious ADRs = 6.5%
4% of hospital bed capacity
Fatality rate = 0.15%
70% avoidable & Cost to NHS £466 million/year
Global vision of Pharmacovigilance
Introduction to Pharmacovigilance 11 & 12 Dec 2011
Dr Amr Saad. Lecture - Head of the
Egyptian Pharmacovigilance Center 22
Global pharmacovigilance system
WHO HQ
National Regulatory Agencies
Uppsala Drug
Monitoring Centre
Global networking in PV
• Vigibase Vigisearch & Vigimine Vigilyze.
• UMC collaboration portal.
• Vigimed.
• Signal reports.
• Periodic newsletters and publications by UMC.
• WHO reports.
• Annaul Global meeting
Introduction to Pharmacovigilance 11 & 12 Dec 2011
Dr Amr Saad. Lecture - Head of the
Egyptian Pharmacovigilance Center 23
Other global collaboration
UMC Publications
Progress in the PV scope
• The science &
activities realting
to the detection,
assessment,
understanding &
prevention of
Adverse Events or
any other drug
related problem
• Adverse reactions
• Lack of effect
- Resistance
- Interaction
- counterfeiting
• Quality problems
• Dependance & abuse
• Poisoning
• Medication errors
Introduction to Pharmacovigilance 11 & 12 Dec 2011
Dr Amr Saad. Lecture - Head of the
Egyptian Pharmacovigilance Center 24
The need for national PV system –
Countries` differences in:
Main Obstacle in PV
• Under and Delayed
Reporting
• International
networking &
Collaboration
Introduction to Pharmacovigilance 11 & 12 Dec 2011
Dr Amr Saad. Lecture - Head of the
Egyptian Pharmacovigilance Center 25
WHO- Drug Monitoring Programme
Founding members 1968
WHO- Drug Monitoring Programme
2005
Introduction to Pharmacovigilance 11 & 12 Dec 2011
Dr Amr Saad. Lecture - Head of the
Egyptian Pharmacovigilance Center 26
WHO- Drug Monitoring Programme
October 2011
WHO members of the programme for
international drug monitoring
Introduction to Pharmacovigilance 11 & 12 Dec 2011
Dr Amr Saad. Lecture - Head of the
Egyptian Pharmacovigilance Center 27
Cumulative numbers of ICSRs in the
global database
Global system in PV
WHO Database
VigiBaseWHO Drug Dictionary
WHO-ARTMedDRA
National Centre
VigiFlow
Intdis
E2B
VigiSearchVigiMine
Introduction to Pharmacovigilance 11 & 12 Dec 2011
Dr Amr Saad. Lecture - Head of the
Egyptian Pharmacovigilance Center 28
Thank you