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.




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




Risk-benefit balance

Unacceptable

acceptable

Emerging safety consideration of

medications

Quality

Safety

Efficacy




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• Withdrawn shortly afterward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.




Phocomelia

Phocomelia cases – 15% Death rate




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”




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




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?




Clinical Development of Medicine

Animal studies (Pre-clinical phase)

• ADME*

• Acute toxicity

• Sub-acute, chronic toxicity

• Carcinogenicity

• Reproductive toxicity

• Mutagenicity

• Teratogenicity




Clinical trial phases

Phase I

Phase II

Phase III

Nu

mb

er

of

pat

ien

ts

Development time

Clinical trial phases




Frequency scale of adverse drug

reactions (ADRs)

Lag time for adverse drug reactions

(ADRs)




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




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)




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)




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




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.




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.




Marketing for the idea of Pharmacovigilance

Marketing for the idea of

Pharmacovigilance

►Part of the practice

►Humanitarian & Ethical concerns

►Economical concern




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




►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




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




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




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




The need for national PV system –

Countries` differences in:

Main Obstacle in PV

• Under and Delayed

Reporting

• International

networking &

Collaboration




WHO- Drug Monitoring Programme

Founding members 1968


2005





October 2011

WHO members of the programme for

international drug monitoring




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




Thank you

2- introduction to pharmacovigilance

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