Introduction to Pharmacovigilance

11 & 12 Dec 2011

The Egyptian Pharmacovigilance Center (EPVC)

Introduction to Pharmacovigilance

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.

Dr Amr Saad. Lecture - Head of the Egyptian Pharmacovigilance Center

Introduction to Pharmacovigilance

11 & 12 Dec 2011

Smooth orientation to Pharmacovigilance concept

Risk/Benefit Balance of medications

Medicines are safe! (X)

Approved medicines are safe! (X) No medicine is safe! (X) No medicine is without risk! ()

Dr Amr Saad. Lecture - Head of the Egyptian Pharmacovigilance Center

Introduction to Pharmacovigilance

11 & 12 Dec 2011

Risk-benefit balance

Unacceptable

acceptable

Emerging safety consideration of medications

Safety

Quality

Efficacy

Dr Amr Saad. Lecture - Head of the Egyptian Pharmacovigilance Center

Introduction to Pharmacovigilance

11 & 12 Dec 2011

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Tranquilliser launched - 1957 First reports of birth defects - 1959 13 reports of birth defects - 1961 Withdrawn shortly afterward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.

Dr Amr Saad. Lecture - Head of the Egyptian Pharmacovigilance Center

Introduction to Pharmacovigilance

11 & 12 Dec 2011

Phocomelia

Phocomelia cases 15% Death rate

Dr Amr Saad. Lecture - Head of the Egyptian Pharmacovigilance Center

Introduction to Pharmacovigilance

11 & 12 Dec 2011

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

Dr Amr Saad. Lecture - Head of the Egyptian Pharmacovigilance Center

Introduction to Pharmacovigilance

11 & 12 Dec 2011

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

Communication

Drug Safety Monitoring

Risk Mgt.

Signal Detection

Dr Amr Saad. Lecture - Head of the Egyptian Pharmacovigilance Center

Introduction to Pharmacovigilance

11 & 12 Dec 2011

Drug safety throughout product life cycle

Preclinical Clinical trial Market authorization Clinical practice Clinical Drug Safety Post Marketing Surveillance
Passive Active

Pharmacovigilance
Tools Spontaneous reports Literature searching

Pharmaco-epidemiology
Tools PMS* studies

Why do we need Pharmacovigilance?

Dr Amr Saad. Lecture - Head of the Egyptian Pharmacovigilance Center

Introduction to Pharmacovigilance

11 & 12 Dec 2011

Clinical Development of Medicine

Animal studies (Pre-clinical phase)

ADME*
Acute toxicity Sub-acute, chronic toxicity Carcinogenicity Reproductive toxicity Mutagenicity Teratogenicity

Dr Amr Saad. Lecture - Head of the Egyptian Pharmacovigilance Center

Introduction to Pharmacovigilance

11 & 12 Dec 2011

Clinical trial phases

Number of patients

Phase III

Phase II Phase I Development time

Clinical trial phases

Dr Amr Saad. Lecture - Head of the Egyptian Pharmacovigilance Center

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Introduction to Pharmacovigilance

11 & 12 Dec 2011

Frequency scale of adverse drug reactions (ADRs)

Lag time for adverse drug reactions (ADRs)

Dr Amr Saad. Lecture - Head of the Egyptian Pharmacovigilance Center

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Introduction to Pharmacovigilance

11 & 12 Dec 2011

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

Dr Amr Saad. Lecture - Head of the Egyptian Pharmacovigilance Center

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Introduction to Pharmacovigilance

11 & 12 Dec 2011

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)

Dr Amr Saad. Lecture - Head of the Egyptian Pharmacovigilance Center

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Introduction to Pharmacovigilance

11 & 12 Dec 2011

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)

Dr Amr Saad. Lecture - Head of the Egyptian Pharmacovigilance Center

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Introduction to Pharmacovigilance

11 & 12 Dec 2011

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

Dr Amr Saad. Lecture - Head of the Egyptian Pharmacovigilance Center

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Introduction to Pharmacovigilance

11 & 12 Dec 2011

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.

Dr Amr Saad. Lecture - Head of the Egyptian Pharmacovigilance Center

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Introduction to Pharmacovigilance

11 & 12 Dec 2011

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.

Dr Amr Saad. Lecture - Head of the Egyptian Pharmacovigilance Center

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Introduction to Pharmacovigilance

11 & 12 Dec 2011

Marketing for the idea of Pharmacovigilance

Marketing for the idea of Pharmacovigilance

Part of the practice Humanitarian & Ethical concerns Economical concern

Dr Amr Saad. Lecture - Head of the Egyptian Pharmacovigilance Center

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Introduction to Pharmacovigilance

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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

Dr Amr Saad. Lecture - Head of the Egyptian Pharmacovigilance Center

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Introduction to Pharmacovigilance

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Economical concerns

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
ADVERSE EFFECTS
US study 1994

Medication Errors

Preventable ARs

Unpreventable ARs

4th 6th cause of death 5% hospital admissions Occur in 11% patients Double cost/length of stay Double mortality rate Less than 1% reported

Quality Problems

Dr Amr Saad. Lecture - Head of the Egyptian Pharmacovigilance Center

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Introduction to Pharmacovigilance

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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

Dr Amr Saad. Lecture - Head of the Egyptian Pharmacovigilance Center

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Introduction to Pharmacovigilance

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Global pharmacovigilance system

WHO HQ

Uppsala Drug Monitoring Centre

National Regulatory Agencies

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

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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

Dr Amr Saad. Lecture - Head of the Egyptian Pharmacovigilance Center

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Introduction to Pharmacovigilance

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The need for national PV system Countries` differences in:

Main Obstacle in PV

Under and Delayed Reporting

International networking & Collaboration

Dr Amr Saad. Lecture - Head of the Egyptian Pharmacovigilance Center

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Introduction to Pharmacovigilance

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WHO- Drug Monitoring Programme Founding members 1968

WHO- Drug Monitoring Programme 2005

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Introduction to Pharmacovigilance

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WHO- Drug Monitoring Programme October 2011

WHO members of the programme for international drug monitoring

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Introduction to Pharmacovigilance

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Cumulative numbers of ICSRs in the global database

Global system in PV

WHO-ART MedDRA

VigiBase

WHO Database

WHO Drug Dictionary

Intdis

VigiFlow
E2B

VigiSearch VigiMine

National Centre

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Introduction to Pharmacovigilance

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Thank you

Dr Amr Saad. Lecture - Head of the Egyptian Pharmacovigilance Center

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