Uniting multisectoral efforts in

pharmacovigilance to improve
public health protection

Dr Vinod Bura, 25th Aug 2020

National Dialogue : Uniting Multisectoral Effort in Pharmacovigilance
To Improve Public Health Protection

1| TITLE from VIEW and SLIDE MASTER | August 25, 2020

 Definition
Pharmacovigilance has been
defined as:

⚫ The science and activities relating

to the detection, assessment,
understanding and prevention
of adverse effects or any other
drug-related problem (WHO).

2| TITLE from VIEW and SLIDE MASTER | August 25, 2020

 What is Pharmacovigilance?

WHO definition:

The science and activities relating to the

detection, assessment, understanding and
prevention of adverse effects or any other
drug-related problem.
This applies throughout the life cycle of a medicine equally to
the pre-approval stage as to the post-approval.

3| TITLE from VIEW and SLIDE MASTER | August 25, 2020

 Risk
⚫No medicinal product is entirely or
absolutely safe for all people, in all
places, at all times. We must always
live with some measure of uncertainty.

4| TITLE from VIEW and SLIDE MASTER | August 25, 2020

 Pharmaco - Vigilance

⚫ Pharmaco = medicine
⚫ Vigilare = to watch
– alert watchfulness
– forbearance of sleep; wakefulness
– watchfulness in respect of danger; care; caution;
circumspection
– the process of paying close and continuous attention

5| TITLE from VIEW and SLIDE MASTER | August 25, 2020

What is the scope of pharmacovigilance?
⚫ improve patient care and safety in relation to the use of medicines,
and all medical and paramedical interventions,

⚫ improve public health and safety in relation to the use of medicines,

⚫ contribute to the assessment of benefit, harm, effectiveness and risk

of medicines, encouraging their safe, rational and more effective
(including cost-effective) use, and

⚫ promote understanding, education and clinical training in

pharmacovigilance and its effective communication to the public

6| TITLE from VIEW and SLIDE MASTER | August 25, 2020

 Medicine Safety

⚫ To undergo treatment you

have to be very healthy,
because apart from your
sickness you have to
withstand the medicine.

Molière

7| TITLE from VIEW and SLIDE MASTER | August 25, 2020

 National Pharmacovigilance Centres

8| TITLE from VIEW and SLIDE MASTER | August 25, 2020

 WHO Programme for International Drug
Monitoring

WHO HQ + WHO
6 Regional Collaborating
offices Centre, Uppsala

National
Centres

9| TITLE from VIEW and SLIDE MASTER | August 25, 2020

 Uppsala Monitoring Center
UMC was established in
Uppsala, Sweden in 1978
as the World Health
Organization
(WHO) Collaborating Centre
for International Drug
Monitoring. UMC
operates the technical and
scientific aspects of the
WHO’s worldwide
pharmacovigilance network.
10 | TITLE from VIEW and SLIDE MASTER | August 25, 2020
 140 countries are members of the WHO
Programme for International Drug Monitoring.

11 | TITLE from VIEW and SLIDE MASTER | August 25, 2020

Substandard and falsified medical products
⚫ Substandard and falsified medical products may cause harm to patients and fail to treat the diseases for
which they were intended.

⚫ They lead to loss of confidence in medicines, healthcare providers and health systems.

⚫ They affect every region of the world.

⚫ Substandard and falsified medical products from all main therapeutic categories have been reported to
WHO including medicines, vaccines and in vitro diagnostics.

⚫ Anti-malarials and antibiotics are amongst the most commonly reported substandard and falsified medical
products.

⚫ Both generic and innovator medicines can be falsified, ranging from very expensive products for cancer
to very inexpensive products for treatment of pain.

⚫ They can be found in illegal street markets, via unregulated websites through to pharmacies, clinics and
hospitals.

⚫ An estimated 1 in 10 medical products in low- and middle-income countries is substandard or falsified.

⚫ Substandard and falsified medical products contribute to antimicrobial resistance and drug-resistant
infections.

12 | TITLE from VIEW and SLIDE MASTER | August 25, 2020

 TB ;- MDR- XDR
HIV;- ARV
Toxicity
AMR
MCH side
effects

13 | TITLE from VIEW and SLIDE MASTER | August 25, 2020

 Adverse event/experience
– WHO definition
Any untoward medical occurrence that may
present during treatment with a
pharmaceutical product but which does not
necessarily have a causal relationship with
this treatment

14 | TITLE from VIEW and SLIDE MASTER | August 25, 2020

 Adverse Reaction to a medicine (ADR)
–WHO Definition
A reaction which is noxious and unintended,
and which occurs at doses normally used in
man for the prophylaxis, diagnosis or therapy
of disease, or for the modification of
physiological function

15 | TITLE from VIEW and SLIDE MASTER | August 25, 2020

 Why do we need pharmacovigilance?
1959 / 61– Epidemia de ▪
focomelia por Talidomida (4.000
– 10.000 casos no mundo, com
15% de mortos)

16 | TITLE from VIEW and SLIDE MASTER | August 25, 2020

 Why do we need pharmacovigilance?

Reason 1:

⚫ Humanitarian concern –
– Insufficient evidence of safety from clinical trials
– Animal experiments
– Phase 1 – 3 studies prior to marketing authorization

17 | TITLE from VIEW and SLIDE MASTER | August 25, 2020

 Drug Development

Clinical development of medicines

Phase I Phase III

20 – 50 healthy volunteers
to gather preliminary data
Animal experiments for
acute toxicity, organ
damage, dose dependence,
metabolism, kinetics,
carcinogenicity,
mutagenicity/teratogenicity
250 – 4000 more varied
patient groups – to
determine short-term safety
and efficacy
Phase II
Phase IV
150 – 350 subjects with
Post-approval studies to
disease - to determine
determine specific safety issues
safety and dosage
recommendations

ion
strat
Preclinical
Phase IV Spontaneous
Animal Phase I Phase II Phase III

Regi
Experiments Post-approval Reporting

Development Post Registration

18 | TITLE from VIEW and SLIDE MASTER | August 25, 2020

 Limitations of phase 1 -3 clinical trials

⚫ limited size: no more than 5000 and often as little

as 500 volunteers
⚫ narrow population: age and sex specific
⚫ narrow indications: only the specific disease
studied
⚫ short duration: often no longer than a few weeks

19 | TITLE from VIEW and SLIDE MASTER | August 25, 2020

Examples of product recalls due to toxicity
⚫ Medicine Year ⚫ Examples of serious and unexpected
adverse events leading to withdrawal
of medicine

⚫ Thalidomide 1965 ⚫ Phocomelia

⚫ Practolol 1975 ⚫ Sclerosing peritonitis

⚫ Clioquinol 1970 ⚫ Subacute nephropathy

⚫ Benoxaprofen 1982 ⚫ Nephrotoxicity, cholestatic jaundice

⚫ Terfenadine 1997 ⚫ Torsade de pointes

⚫ Rofecoxib 2004 ⚫ Cardiovascular effects

⚫ Veralipride 2007 ⚫ Anxiety, depression, movement

disorders

20 | TITLE from VIEW and SLIDE MASTER | August 25, 2020

 Why do we need pharmacovigilance?

Reason 2

• Medicines are supposed to save lives

Dying from a disease is sometimes unavoidable; dying

from a medicine is unacceptable. Lepakhin V. Geneva
2005

21 | TITLE from VIEW and SLIDE MASTER | August 25, 2020

⚫ UK:

It has been suggested that ADRs may cause 5700 deaths per
year in UK.
Pirmohamed et al, 2004
⚫ US:

ADRs were 4th-6th commonest cause of death in the US in 1994

Lazarou et al, 1998

22 | TITLE from VIEW and SLIDE MASTER | August 25, 2020

 ⚫ 125 Patients

⚫ 24 Patients experienced ADRs (19%)

(59%) were avoidable

23 | TITLE from VIEW and SLIDE MASTER | August 25, 2020

 Why do we need pharmacovigilance?

Reason 3: ADRs are expensive !!

24 | TITLE from VIEW and SLIDE MASTER | August 25, 2020

 ⚫ 6.5% of admissions are due to ADRs

⚫ Seven 800-bed hospitals are occupied by ADR

patients

Cost £446 million per annum

25 | TITLE from VIEW and SLIDE MASTER | August 25, 2020

 Cost of ADRs in the US?
⚫ Cost of drug related morbidity and mortality exceeded
$177.4 billion in 2000 (Ernst FR & Grizzle AJ, 2001: J
American Pharm. Assoc)

⚫ ADR related cost to the country exceeds the cost of the

medications themselves

26 | TITLE from VIEW and SLIDE MASTER | August 25, 2020

 Why do we need pharmacovigilance?

Reason 4:

Promoting rational use of

medicines and adherence

27 | TITLE from VIEW and SLIDE MASTER | August 25, 2020

 Prescription

31 December 2019

Re: Mr Joseph Bloggs

1) abacavir + lamivudine + zidovudine 1 BD
2) atenolol 100 mg/d
3) acetylsalicylic acid 150mg/d
4) cerivastatin 10 mg/d
5) gemfibrozil 200 mg/d
6) metformin 500 mg/d
7) fluoxetine 50 mg/d
8) Sildenafil

28 | TITLE from VIEW and SLIDE MASTER | August 25, 2020

Italian
Cohort
Main reasons of discontinuation
I C O of first HAART regimen within
N A 1st year: ICONA
Naive
Antiretroviral

Toxicity
Failure
Non-adherence
Other
Continued

Monforte et al. AIDS 1999

29 | TITLE from VIEW and SLIDE MASTER | August 25, 2020

 Why do we need pharmacovigilance?

Reason 5: Ensuring public confidence

If something can go wrong, it will –

Murphy's law

30 | TITLE from VIEW and SLIDE MASTER | August 25, 2020

 ALLEGATION:
Known about SSRI
prescribing at
unsafe doses for a
decade

Guardian Weekly
March 18-24 2004

31 | TITLE from VIEW and SLIDE MASTER | August 25, 2020

Safety concerns now high on the agenda of ALL
countries

⚫ Developed countries ⚫ Developing countries

32
32 | TITLE from VIEW and SLIDE MASTER | August 25, 2020
 Why do we need pharmacovigilance?

Reason 6: Ethics
To know of something that is harmful to another person
who does not know, and not telling, is unethical

33 | TITLE from VIEW and SLIDE MASTER | August 25, 2020

34 | TITLE from VIEW and SLIDE MASTER | August 25, 2020
 The Multisectoral efforts to improve

⚫ General health and medicines ⚫ pharmaceutical companies

vigilance must be embedded in
the life of health providers and all ⚫ research organisations
related organizations.
⚫ public health programmes
⚫ This implies a constant state of
watchfulness to recognize when ⚫ hospitals
things are going wrong, to take
⚫ pharmacies
action to solve immediate
problems, and to share ⚫ Media
information about the causes of
harm to influence future policy ⚫ all health workers and
and practice. providers
35 | TITLE from VIEW and SLIDE MASTER | August 25, 2020
 Pharmacovigilance is Essential

THANK
YOU

36 | TITLE from VIEW and SLIDE MASTER | August 25, 2020