Transcript Why do we need Pharmacovigilance?

Why do we need
Pharmacovigilance?
Samira Saleh
Prof. of Pharmacology
Faculty of Pharmaceutical Sciences
and Pharmaceutical Industries,
Future University
Egypt
5th Global Pharmacovigilance Summit, 8-29 April 2016, Dubai, UAE
Outline
Theme
Ensure safer drugs to the healthcare community
Adverse Drug Reactions
 Why is detection & assessment of ADRs
inadequate in clinical trials?
Pharmacovigilance
 Why do we need pharmacovigilance
The study of ADRs is the
concern of the field of
pharmacovigilance
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.
Types of ADRs
1. Type A:
Augmented pharmacologic
effects (dose-dependent and
predictable)
2. Type B:
Bizarre effects (dose independent
& unpredictable)
3. Type C:
4. Type D:
5. Type E:
6. Type F:
7. Type G:
Chronic effects
Delayed effects
End-of-treatment effects
Failure of therapy
Genetic reactions
Possible causes of ADRS
1. Intrinsic
Idiosyncrasy
Mutagenicity
Carcinogenicity Teratogenicity
2. Extrinsic
Adulterations, contamination
3. Underlying medical conditions
4. Interactions
5. Wrong use
Serious and severe
Serious (FDA): when it meets one of the following
criteria:
1. Results in death
2. Life-threatening
3. Requires inpatient hospitalization or prolongation of
hospitalization
4. Results in disability - or permanent change, impairment,
damage or disruption in the patient's body
function/structure, physical activities or quality of life
5. Results in congenital abnormalities
6. Requires intervention to prevent permanent damage
Severity: intensity of the adverse effect
Economic impact of ADRs
• The cost to the country of ADRs
may exceed the cost of the
medications themselves
• 30-60 % of ADRs may be
preventable
Before drugs become available to the
patients, they are subjected to rigorous
clinical studies.
Preclinical
Research
Postmarketing
Surveillance
in real life
patients
However, some adverse drug reactions
(ADRs) are often detected ONLY after
marketing.
Limitations of clinical trials
1. Number of patients is limited: ~ 5000
2. Narrow population: Specific age and
sex
3. Narrow indications: only those having
the specific disease studied
4. Short duration: often no longer than a
few weeks
Why is detection & assessment of ADRs
inadequate in clinical trials?
Discovering ADR depends on:
Frequency of occurrence
Number of patients exposed to the drug
Clinical trials are usually short-term studies
conducted in a few hundred patients before
marketing a drug. Therefore, further investigation on
ADRs must be pursued in the post-marketing phase.
Pharmaco - Vigilance
Pharmaco (Greek): drug
Vigilance (Latin):
– to keep awake or alert
– to keep watch
– the process of paying close and
continuous attention
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.
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
Aims of pharmacovigilance
1. Identify previously unrecognized adverse
effects or changes in the patterns of adverse
effects
2. Assess the risks and benefits of medicines in
order to determine what action, if any, is
necessary to improve their safe use
3. Provide information to healthcare
professionals and patients to optimize safe
and effective use of medicines
– 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
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
Pharmacovigilance is
gaining importance as
the number of stories
of drug recalls
increases
Examples of licensed drugs withdrawn
after marketing for drug safety reasons
1. Thalidomide
2. Practolol
(1965)
(1975)
3. Phenformin
4. Rofecoxib
(1982)
(2004)
5. Veralipride
(2007)
6. Troglitazone (Rezulin)
7. Rosiglitazone
(2010(
Phocomelia
Sclerosing
peritonitis
Lactic acidosis
Cardiovascular
effects
Anxiety,
depression,
movement disorders
(2000) Hepatitis
Increased risk of
MI and death
from CV causes
Pharmacovigilance cycle
Collection &
Management of data
Analysis &
Evaluation of data
Acting to protect
public health
Actions taken from the PV findings
include
1. Restriction in use
2. Changes in the specified dose of the medicine
3. Introduction of specific warnings in the
product information
4. Changing the legal status of a medicine, e.g.,
from over-the-counter to prescription only
5. Product recall: In rare cases, removal of the
medicine from the market, if the risks of a
medicine are found to outweigh the benefits
International collaboration
in the field of pharmacovigilance
•
•
•
•
WHO runs the Uppsala Monitoring
Centre( started in 1968, moved to
Uppsala Sweden in 1978)
European Union runs the European
Medicines Evaluation Agency (EMEA)
United States, the FDA is responsible
for monitoring post-marketing studies.
Egyptian PV center
Growth of membership of
International Drug Monitoring
Programme since 1968
WHO drug monitoring programme, March 2006
As for August 2011: 106 members and 33
awaiting for full membership
Cumulative number of reports
Establishment of the Egyptian
Pharmacovigilance Center (EPVC)
The Egyptian Pharmacovigilance Center
(EPVC)
December 2009
‫مركز اليقظة الدوائية المصري‬
2009 ‫ديسمبر‬
http://epvc.gov.eg
Personnel training is ongoing in order achieve the
highest level of competency
Middle East Members
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
Morocco
1992
Tunisia
1993
Oman
1995
Iran
1998
Egypt
2001
Jordan
2002
Sudan
2008
Saudi Arabia
2009
Iraq
2010
United Arab Emirates
The First Eastern Mediterranean Region (EMR)/Arab Countries Meeting of
pharmacovigilance was held in Rabat Morocco, from 22 to 26 September 2014.
Drugs - Real World Outcomes (2015)
Harmonized
Arab PV
definitions
and
terms
Why is it important for countries to
support their own PV programs?
1. Citizens may have unique traditions and diets
influencing reactions to medications
2. ADRs may be associated with traditional or
herbal remedies unique to each country
3. In some cases, ADRs to certain drugs may
only occur in particular ethnic groups
4. Alternate brands of therapy may be imported
or manufactured & differ in ingredients or
production processes
How to report?
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 .
Essential information included
on the yellow card
1. Patient details
2. Suspected drug
3. Suspected reaction
4. Reporter details
What should be reported?
1. All suspected reactions including minor
ones
2. All serious, unexpected, unusual ADRs
3. Change in frequency of a given reaction
4. All suspected drug-drug, drug-food, drug
food supplements interactions
5. ADRs associated with drug withdrawal
6. ADRs due to medication errors
7. ADRs due to lack of efficacy or suspected
pharmaceutical defect
Why is the yellow card scheme
important?
1. The scheme acts as an early warning
system for the identification of
previously unrecognized reactions
1. It enables to identify risk factors,
outcomes of the ADR and other
factors that may affect clinical
management
Who can report?
► Patients, patients relatives or patients
carers
► Health care professionals (physicians,
dentists, pharmacists, nurses)
► Manufacturers
► Authorities
Report to whom?
►
►
►
►
►
►
Regulatory Authority
Industry, manufacturers
Health professionals
Patient organizations
General public
Social security
Cumulative reports as of April
2004
Causality assessment
How likely is this medication the cause
of this problem in this particular
patient?
The Naranjo algorithm
This is a questionnaire for determining the
likelihood of whether an ADR is actually due
to the drug rather than the result of other
factors.
Probability is assigned by a score (definite,
probable, possible or doubtful).
Naranjo CA, Busto U, Sellers EM, et al. (1981).
A method for estimating the probability of adverse drug reactions
Clin. Pharmacol. Ther. 30 (2): 239–45.
Naranjo scoring system
Factors to be considered (Questionnaire)
1. Are there previous conclusive reports on this
reaction?
2. Did the adverse event appear after the
suspected drug was given?
3. Did the adverse reaction improve when the
drug was discontinued or a specific
antagonist was given?
4. Did the adverse reaction appear when the
drug was readministered?
5. Are there alternative causes that could have
caused the reaction?
Questionnaire (cont)
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?
6.
Categories of causality (Scoring)
Definite ADR
>9
Probable ADR
5-8
Possible ADR
1-4
Doubtful ADR
0
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
• Countries have to support their own
national pharmacovigilance.
• Each country should support its own PV
program
A successfully implemented
pharmacovigilance centre can
minimize, prevent and improve the use
of drugs by discovering ADRs at the
level of general public use.
Ensure Safer Drugs to the Healthcare
Community
Thank you for your attention