Mukesh Dheda [email protected]

Byte Conference Centre 19 Jun 2009

Pharmaco igilance

Disclaimer / Caveat

The views expressed are those of the presenter.

Pharmacovigilance Assessment of the effectiveness of these interventions

Size and severity of the problem

25 studies 1970-95  Hospital admissions due to ADRs  4.2 - 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 NPC

NADEMC MEDUNSA OTHER PV CENTRES

Pharmacovigilance Whose Responsibility?

 Responsibility is shared between  Manufacturer, 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 problems  quantifying risks  detection of increases in frequency  identification of risk factors  assessing risk-benefit  preventing 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 Activity in an adult individual (100 %) Most cytochromes P450s 50 Conjugation with glucuronic acid Conjugation with sulphate Cytochrome P450 3A7 0

 A Rane Sep 03

Birth

Paracetamol metabolism

in fetal and neona tal period

sulfate sulfate

in adult life

PARACETAMOL glucuronide oxidised metabolite glutathione conjugate PARACETAMOL glucuronide oxidised metabolite glutathione conjugate

35 7 GRAPEFRUIT JUICE WATER Bailey et al. Br J Clin Pharmacol; 1998; 46: 101-110

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 Trials  Observational 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 reporting

Primary method --- reasons

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

Spontaneous ADR reporting

disadvantages

 under-reporting  difficult to detect  delayed reactions  reactions 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 Africa  May 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 reports  Lack of efficacy reports – with details of event not given  No 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: 700,000 Accidental deaths caused by physicians per year: 120,000 Accidental deaths per physician: 0.171

(U.S. Dept.of Health & Human Services) Number of gun owners in the US: 80,000,000 Number of accidental gun deaths per year (all age groups): 1,500 Accidental 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."

5 4 3 2 1 0

South Africa is part of an international PV system

Reports in VigiBase 1968 - 2008

Country Distribution in VigiBase October 2008 Spain 2% Sweden 2% Thailand 2% Netherlands 2% Australia 4% Canada 5% France 5% Germany 6% United States 50% United Kingdom 11% Other Countries 11%

Average ADR-reports /1 million Inhabitants

2003 - 2007

1000 900 800 700 600 500 400 300 200 100 0 N ew Ze al N an et d he rla nd s A us tra lia C an ad S w a itz er U la ni nd te d S ta te s S w ed en N or w ay U Fr ni an te ce d K in gd om D en m ar k S in ga po re Ire la nd C ub a Fi nl an d Th ai la nd G er m an y S pa in Ic el an d C ro at ia

Reporting Rates for South Africa (< 100 reports/million inhabitants)

Thank you for your attention!

The future