Pharmaco igilance

Mukesh Dhedadhedam@health.gov.za

Byte Conference Centre 19 Jun 2009

Disclaimer / Caveat

The views expressed

are those of the presenter.

Pharmacovigilance

Ass

essm

ent

Und

erst

andi

ng

Det

ecti

on

Pre

vent

ion

Assessment of the effectiveness of these interventions

Size and severity of the problem

25 studies 1970-95

Hospital admissions due to ADRs4.2 - 6.0% with a median of 5.8%

Pharmacoepidem & Drug Safety 6; suppl 3: s71-s77 (1997)

Somerset Hospital Study

N=665 patients

Hospital admissions due to ADRs (6.3%) Patients developed an ADR in hospital

(6.3%).

Mehta U et al. Br J Clin Pharmacol 2007; 65(3):396-406

National pharmacovigilance

MEDUNSA

NPC

NADEMC

OTHER PV CENTRES

Pharmacovigilance Whose Responsibility?

Responsibility is shared betweenManufacturer, distributor, regulatory authority,

HCPs, media and consumers

Responsibility is retained throughout the product life cycle even beyond the point of use

Role and functions may differ between these players

What is industry’s role?

Common goals of Regulators and Industry

early detection of unknown safety problemsquantifying risksdetection of increases in frequencyidentification of risk factorsassessing risk-benefitpreventing or minimising patient harm

Why South Africa needs its own

Pharmacovigilance programme?

Differences in: Access, distribution and use (e.g. indications, dose,

availability) Genetics, diet, traditions, language, Culture of medicine and drug use Pharmaceutical quality and composition (excipients) of

products Profile of diseases prevalent in the population Health care infrastructure, skilled human resources and

access to information, regulatory enforcement capacity

One Size doesn’t fit all…

A presentation on Promoting Safety of Medicines for Children by Anders Rane, National centres meeting, Sweden, 2008.

Development of drug metabolising enzymes in man

%100

50

0

Activity in an adult individual (100 %)

Birth

Most cytochromesP450s

Cytochrome P450 3A7

Conjugation withglucuronic acid

Conjugation with sulphate

A Rane Sep 03

Paracetamol metabolism

sulfate PARACETAMOL glucuronide

oxidised metabolite

glutathione conjugate

sulfate PARACETAMOL glucuronide

oxidised metabolite

glutathione conjugate

in fetal and

neona-tal

period

in adult

life

35

7

Bailey et al. Br J Clin Pharmacol; 1998; 46: 101-110

WATER

GRAPEFRUIT JUICE

This is your medicine. Tell me if you will

have any adverse

reactions and I’ll give you another

drug.

Sorry doc, but…. could you please give me the other drug just now?

Major Pharmacovigilance Methods in SA

Individual Case Reports (Spontaneous reports)

Clinical TrialsObservational Cohort studies (controlled and

uncontrolled e.g. CEM) Case control studies

Spontaneous ADR reporting

Principle

The alert health professional connects an undesirable medical event with drug exposure

SUSPICION

Reports suspicion to information collecting centre

Spontaneous ADR reportingPrimary method --- reasons

large population all medicines hospital and out-patient care long perspective patient analyses possible non-interventional low cost

Spontaneous ADR reportingdisadvantages

under-reporting difficult to detect

delayed reactionsreactions with high background

incidence

number of exposed unknown bias

Safety reporting in South Africa

Post-Registration Safety Reporting in SA

Based on Regulation 37 of Act 101 (1965)Guidelines on Reporting Adverse Drug

Reactions in South AfricaMay 2003

Good Pharmacovigilance Practice includes…

A culture of safety awareness among sales, regulatory and marketing staff

A proper data management system for ADR reports Procedures to ensure that appropriate and timely

action can be taken including a crisis management plan

Compliance with local regulations and guidelines Compilation/co-ordination of safety reports and

analyses requested by regulatory authority A responsible appropriately trained person for pre-

and post-marketing surveillance (if not a HCP, should have access to a medically qualified person)

Inform MRA of who this individual is

Do not submit a report unless it has the following minimum information…

An identifiable source (reporter). This should include the name , address

and qualification.An identifiable patient.

Name, initials or reference number. Suspected product(s).Suspected reaction(s).Reports with all minimum info can still

be of poor quality!

What constitutes a good quality report?

Patient clinical condition (i.e. underlying disease, co-morbidity, gender, age, weight, renal function etc)

Drug information (include all concurrent medication e.g. OTC, complementary and chronic meds not suspected by reporter)

Event details (include baseline and subsequent lab data, objective evidence of the event if any, response to dechallenge and rechallenge, documented alternative causes etc)

Reporter qualifications, address and if patient referred, then referring doctor to enable follow-up and further investigation

What happens to reported ADR

On receipt ---assign number Acknowledgement Database Evaluated individually and also check for similar

reports Recommendation made to committee/council Act on recommendation (draft MSA, PI changes,

request additional data from applicant, inform other departments in DoH)

Opportunities to Improve Individual Case Reporting

Pregnancy exposures with no outcome reported

Duplication of reportsLack of efficacy reports – with details of event

not givenNo identifiable patient, reporter, ADR, or drug Inadequate clinical data/ summarised clinical

data submitted as ADR report instead of complete report submitted by initial reporter

Name of initial reporter anonymised – not in keeping with guidelines

Opportunities to improve communication of post-registration safety information

Published safety studies and other regulatory decisions – communication delayed or no communication

Changes to risk-benefit profile or where significant PI changes are required (i.e. changes in conditions of registration) –within 3 calendar days

Current guidelines do request that all safety data derived from risk management activities are submitted when regulatory action is necessary

Doctors v. Gun Owners

Number of physicians in the US: 700,000Accidental deaths caused by physicians per year: 120,000Accidental deaths per physician: 0.171(U.S. Dept.of Health & Human Services)

Number of gun owners in the US: 80,000,000Number of accidental gun deaths per year (all age groups): 1,500Accidental deaths per gun owner: 0.0000188

Statistically, doctors are approximately 9,000 times more dangerous than gun owners

"Not everyone has a gun, but just about everyone needs a doctor."

Reports in VigiBase 1968 - 2008

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1968

1970

1972

1974

1976

1978

1980

1982

1984

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1988

1990

1992

1994

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1998

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2008

Million r

eport

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South Africa is part of an international PV system

Country Distribution in VigiBaseOctober 2008

Spain2%

United States50%

United Kingdom11%

Other Countries11%

Netherlands2%

Thailand2%

Germany6%

France5%

Canada5%

Australia4%

Sweden2%

0

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200

300

400

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900

1000

Average ADR-reports /1 million Inhabitants2003 - 2007

Reporting Rates for South Africa

(< 100 reports/million inhabitants)

Thank you for your attention!

The future