1. World Health Organization
22 May 2018
The need for Pharmacovigilance Mary R Couper and Shanthi Pal Quality Assurance and Safety of Medicines

3. World Health Organization
Medicine Safety
22 May 2018
To undergo treatment you have to be very healthy, because apart from your sickness you have to withstand the medicine.
Molière

4. 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.

5. What is Pharmacovigilance?
World Health Organization
What is Pharmacovigilance?
22 May 2018
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.

6. 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

7. 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

8. 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

9. 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

10. Why do we need pharmacovigilance?

11. 1959 / 61– Epidemia de focomelia por Talidomida (4. 000 – 10
1959 / 61– Epidemia de focomelia por Talidomida (4.000 – casos no mundo, com 15% de mortos)

12. 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

13. Drug Development

14. 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

15. Examples of product recalls due to toxicity
Medicine Year
Thalidomide 1965
Practolol 1975
Clioquinol 1970
Benoxaprofen 1982
Terfenadine 1997
Rofecoxib 2004
Veralipride 2007
Examples of serious and unexpected adverse events leading to withdrawal of medicine
Phocomelia
Sclerosing peritonitis
Subacute nephropathy
Nephrotoxicity, cholestatic jaundice
Torsade de pointes
Cardiovascular effects
Anxiety, depression, movement disorders

16. 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

17. UK:
US:
It has been suggested that ADRs may cause 5700 deaths per year in UK.
Pirmohamed et al, 2004
ADRs were 4th-6th commonest cause of death in the US in 1994
Lazarou et al, 1998

18. World Health Organization
22 May 2018
125 Patients
24 Patients experienced ADRs (19%)
Intro 2
(59%) were avoidable

19. Why do we need pharmacovigilance?
Reason 3: ADRs are expensive !!

20. Cost £446 million per annum
6.5% of admissions are due to ADRs
Seven 800-bed hospitals are occupied by ADR patients
Cost £446 million per annum

21. 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

22. Why do we need pharmacovigilance?
Reason 4:
Promoting rational use of medicines and adherence

23. HIV Clinic 2005 Re: Mr Joseph Bloggs
Prescription
Dr A. Who 31 December 2000
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
Sildenafil
HIV Clinic 2005

24. Italian
Cohort
Main reasons of discontinuation of first HAART regimen within st year: ICONA I C O N A
Naive
Antiretroviral
Monforte et al. AIDS 1999

25. Why do we need pharmacovigilance?
Reason 5: Ensuring public confidence
If something can go wrong, it will – Murphy's law

26. World Health Organization
22 May 2018
ALLEGATION:
Known about SSRI prescribing at unsafe doses for a decade
disaster!!
Guardian Weekly
March

29. Safety concerns now high on the agenda of ALL countries
World Health Organization
Safety concerns now high on the agenda of ALL countries
22 May 2018
Developed countries
Developing countries
PV in Emerging Countries, CPT th July 2008
Need for Pharmacovigilance
Freetown, Sierra Leone 19th Aug. 2008 29 29 29

30. 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

31. Consequence Not reporting a serious unknown reaction is unethical
valid for everyone
patient
health professional
manufacturer
authorities

32. Pharmacovigilance is Essential