The need for Pharmacovigilance Mary R Couper and Shanthi Pal Quality Assurance and Safety of Medicines

1. The need for PharmacovigilanceMary R Couper and Shanthi PalQuality Assurance and Safety of Medicines

3. Medicine Safety • 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? 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 – 10.000 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. 125 Patients • 24 Patients experienced ADRs (19%) (59%) were avoidable

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

20. 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 • 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

24. Main reasons of discontinuation of first HAART regimen within 1st year: ICONA Italian Cohort 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. ALLEGATION: Known about SSRI prescribing at unsafe doses for a decade disaster!! Guardian Weekly March 18-24 2004

29. Safety concerns now high on the agenda of ALL countries Developed countries Developing countries PV in Emerging Countries, CPT2008 29th July 2008 Need for Pharmacovigilance Freetown, Sierra Leone 19th Aug. 2008 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