1. Why do we need Pharmacovigilance?
Samira Saleh
Prof. of Pharmacology
Faculty of Pharmacy
Cairo University

2. Before drugs become available to the patients, they are subjected to rigorous clinical studies.
However, some adverse drug reactions (ADRs) are often detected ONLY after marketing.

3. The study of ADRs is the concern of the field known as pharmacovigilance

5. Adverse drug reactions
ADR is defined as any harm associated with the use of given drugs at a normal dosage during normal use.
ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs.
The meaning of ADR differs from the meaning of "side effect ", as this last expression might also imply that the effects can be beneficial.

6. Types of ADRs
Type A: Augmented pharmacologic effects (dose dependent and predictable)
Type B: Bizarre effects (dose independent & unpredictable)
Type C: Chronic effects
Type D: Delayed effects
Type E: End-of-treatment effects
Type F: Failure of therapy
Type G: Genetic reactions

7. Serious and severe Serious (FDA): when the patient outcome:
Death
Life-threatening
Hospitalization
Disability - or permanent change, impairment, damage or disruption in the patient's body function/structure, physical activities or quality of life
Congenital abnormalities
Requires intervention to prevent permanent damage
Severity: intensity of the adverse effect

8. Possible causes of ADRS
Intrinsic Idiosyncrasy Mutagenicity Carcinogenicity Teratogenicity
Extrinsic Adulterations, contamination
Underlying medical conditions
Interactions
Wrong use

9. Economic impact of ADRs
In the USA, the cost of drug-related morbidity and mortality exceeded billion dollars in 2000
(Ernst FR & Grizzle AJ, 2001: J American Pharm Assoc)
The cost to the country of ADRs may exceed the cost of the medications themselves
30-60 % of ADRs may be preventable

10. Definition of Pharmacovigilance
PV is the science and activities dealing with the detection, assessment, understanding and prevention of adverse effects of drugs.
It has been widened to include biological products, herbals, traditional and complementary medicines.

11. Pharmaco - Vigilance Pharmaco (Greek): drug Vigilance (Latin):
to keep awake or alert
to keep watch
the process of paying close and continuous attention

12. Why do we need pharmacovigilance?
Reason 1: Insufficient evidence of safety
Animal experiments
Clinical trials prior to marketing
Reason 2: Dying from a disease may be inevitable, dying from a medicine is unacceptable (WHO,2005)
Reason 3: ADR are expensive

13. Limitations of clinical trials
Number of patients is limited: ~ 5000
Narrow population: Specific age and sex
Narrow indications: only those having the specific disease studied
Short duration: often no longer than a few weeks

15. A lesson from history 1959 – 1961 thalidomide 4,000 - 10, 000 cases of
phocomelia (congenital limb defects)
This lead to withdrawal of the drug from the market

16. Pharmacovigilance is gaining importance as the number of stories of drug recalls increases

17. Examples of product recalls due to toxicity
Thalidomide (1965) Phocomelia
Practolol (1975) Sclerosing peritonitis
Phenformin (1982) Lactic acidosis
Rofecoxib (2004) cardiovascular effects
Veralipride (2007) Anxiety, depression, movement disorders
Rosiglitazone (2010 ( Increased risk of MI and death from CV causes

18. Pharmacovigilance Aims of Pharmacovigilance Pharmacovigilance cycle
Regulatory actions to minimize risk
WHO members of the drug monitoring programme
The Egyptian Pharmacovigilance Center
Middle East Members
Top 10 contributors to the WHO database
Yellow Card Scheme
What should be reported?
Who can report?
Report to whom?
Causality assessment

19. Aims of pharmacovigilance
Identify previously unrecognized adverse effects or changes in the patterns of adverse effects
Assess the risks and benefits of medicines in order to determine what action, if any, is necessary to improve their safe use
Provide information to healthcare professionals and patients to optimize safe and effective use of medicines

20. Thus, the ultimate purpose of ADR reporting and monitoring is to reduce risks associated with drug prescribing and administration
Improve patient care and patient safety
Communication with international institutions working in pharmacovigilance

21. Pharmacovigilance cycle
Collecting the data
Analysis of the data
► Collection & management of data on the safety of medicines ►Analysis of the data to detect ‘signals’
►Evaluation of the data ►Decision making with regard to safety issues
►Acting to protect public health (including regulatory action)
►Communicating with stakeholders
►Auditing, both of the outcomes of action taken and of the key
Collection & management of data on the safety of medicines
►Analysis of the data to detect ‘signals’
►Evaluation of the data
►Decision making with regard to safety issues
Acting to protect public health
Decision making with regard to safety issues

22. Changes that occur from the PV findings include
Restriction in use
Changes in the specified dose of the medicine
Introduction of specific warnings in the product information
Changing the legal status of a medicine, e.g., from over-the-counter to prescription only
In rare cases, removal of the medicine from the market, if the risks of a medicine are found to outweigh the benefits

23. International collaboration in the field of pharmacovigilance
WHO runs the Uppsala Monitoring Centre (Started in 1968, Located in Uppsala Sweden)
European Union runs the European Medicines Evaluation Agency (EMEA)
United States, the FDA is responsible for monitoring post-marketing studies.
Egyptian PV center

24. Growth of membership of International Drug Monitoring Programme since 1968

25. As for August 2011: 106 members and 33 awaiting for full membership

26. WHO drug monitoring programme, 2001
As for August 2011: 106 members and 33 awaiting for full membership

27. Establishment of the Egyptian Pharmacovigilance Center (EPVC)
December 2009
مركز اليقظة الدوائية المصري
ديسمبر 2009

28. Middle East Members Morocco 1992 Tunisia 1993 Oman 1995 Iran 1998
Egypt
Jordan
Sudan
Saudi Arabia 2009
Iraq

30. Why is it important for countries to support their own PV programs?
Citizens may have unique traditions and diets influencing reactions to medications
ADRs may be associated with traditional or herbal remedies unique to each country
In some cases, ADRs to certain drugs may only occur in particular ethnic groups
Alternate brands of therapy may be imported or manufactured & differ in ingredients or production processes

31. Yellow Card Scheme
The Yellow Card Scheme is the UK system for collecting information on suspected ADRs.
The Scheme was founded in 1964 after the thalidomide disaster.

32. Essential information to include on a yellow card
Patient details
Suspected drug
Suspected reaction
Reporter details

34. Why is the yellow card scheme important?
The scheme acts as an early warning system for the identification of previously unrecognised reactions
It enables to identify risk factors, outcomes of the ADR and other factors that may affect clinical management

35. What should be reported?
All suspected reactions including minor ones
All serious, unexpected, unusual ADRs
Change in frequency of a given reaction
All suspected drug-drug, drug-food, drug food supplements interactions
ADRs associated with drug withdrawal
ADRs due to medication errors
ADRs due to lack of efficacy or suspected pharmaceutical defect

36. Who can report? Patients, patients relatives or patients carers
Health care professionals (physicians, dentists, pharmacists, radiographers, nurses)
Manufacturers
Authorities

37. Report to whom? ► Regulatory Authority ► Industry, manufacturers
► Health professionals
► Patient organizations
► General public
► Social security

38. Cumulative reports as of April 2004

39. Causality assessment
How likely is this medication the cause of this problem in this particular patient?

40. Naranjo’s algorithm

41. Questionnaire Are there previous conclusive reports on this reaction?
Did the adverse event appear after the suspected drug was given?
Did the adverse reaction improve when the drug was discontinued or a specific antagonist was given?
Did the adverse reaction appear when the drug was readministered?
Are there alternative causes that could have caused the reaction?

42. Questionnaire (cont)
6. Did the reaction reappear when a placebo was given?
7. Was the drug detected in any body fluid in toxic concentrations?
8. Was the reaction more severe when the dose was increased, or less severe when the dose was decreased?
9. Did the patient have a similar reaction to the same or similar drugs in any previous exposure?
10. Was the adverse event confirmed by any objective evidence?

43. Scoring Definite ADR > 9 Probable ADR 5-8 Possible ADR 1-4
Doubtful ADR 0

44. Take home message
Pharmacovigilance is a dynamic clinical and scientific discipline
ADR reporting is the cornerstone pharmacovigilance activity
The majority of global information related to ADRs arises from Western countries
Each country should support its own PV program

45. A successfully implemented pharmacovigilance centre can minimize, prevent and improve the use of drugs by discovering ADRs at the level of general public use.

46. Thank you