Pharmacovigilance
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- Words: 1,456
- Pages: 31
Dr.manjunath Associate professor SSMC Tumkur
History • 1961 - thalidomide disaster • 1968 – WHO pilot research project for international drug monitoring • 1971 – WHO meeting 1.to advocate establishment of national centers for drug monitoring 2.to provide guidelines 3.to identify the contribution that national centers might take to the international system
Contd. • 1984 – international society of pharmacoepidemiology • 1992 – european society of pharmacovigilance • 2002 – WHO pharmacovigilance • 2004 – national pharmacovigilance advisory committee (NHAC) with DGHS as chairman and drug controller general of india as member secretary • 24 peripheral centers, 6 regional centers and 2 zonal centers
Widening horizons • Illegal sale of medicines and drugs of abuse over internet • Increasing self medication practices • Widespread manufacture and sale of counterfeit and substandard medicines • Increasing use of traditional medicines outside the confines of traditional culture of use • Increasing use medicines of different systems with potential for drug interactions
Post marketing surveillance • Monitoring of drug safety after introducing into the market through various systems • Need 1.To assess risk benefit ratio 2.To confirm safety and efficacy 3.To detect less common adverse effects
Methods of surveillance • Anecdotal reporting • Voluntary reporting • Intensive event reporting • Cohort studies (prospective) • Case control studies (retrospective) • Population statistics • Meta-analysis
Organizations involved • WHO – collaborating center for international drug monitoring is Uppsala monitoring centre provides activities and events in PV • CIOMS – council for international organizations of medical sciences-safety information communication between regulators and industries. • ICH – international conference on harmonization discusses scientific and technical aspects of product registration. • WHO-ART – WHO adverse reaction terminology for coding clinical information to drug therapy.
Frequency of ADR • Very common>=1/10 • Common >=1/100 and <1/10 • Uncommon >=1/1000 and <1/100 • Rare >=1/10000 and <1/1000 • Very rare <1/10000
Causality assessment • Certain : proven on dechallenge and rechallenge • Probable : dechallenge confirms.cannot rechallenge • Possible : can be explained by concurrent disease or other drugs • Unlikely : not documented in literature • Unclassified : additional data is awaited so not documented • Unclassifiable : additional data has come but not fit into any categories
Methods of causality assessment • WHO assessment scale • Naranjo’s scale • European ABO system • Karch and Lasagna’s scale • Kramer scale • Bayesian network • Yale logarithm • Spanish imputation system
question 1
Are there previous conclusion reports on this
Yes
No
+1
0
0
Don’t know
reaction? 2
Did the adverse event appear after the suspect drug was administered?
+2
-1
0
3
Did the AR improve when the drug was discontinued or a specific antagonist was administered?
+1
0
0
4
Did the AR reappear when drug was readministered?
+2
-1
0
5
Are there alternate causes [other than the drug] that -1 could solely have caused the reaction?
+2
0
6
Did the reaction reappear when a placebo was given?
-1
+1
0
7
Was the drug detected in the blood [or other fluids]
+1
0
0
in a concentration known to be toxic? 8
Was the reaction more severe when the dose was increased, or less severe when the dose was decreased?
+1
0
0
9
Did the patient have a similar reaction to the same
+1
0
0
+1
0
0
or similar drugs in any previous exposure? 10
Was the adverse event confirmed by objective
Interpretation • > 9 = definite • 5-8 = probable • 1-4 = possible • 0 = unlikely
Schedule Y requirement • Unsuspected adverse event is communicated from 1.Sponsor to regulatory authorities within 14 days 2. Investigator to sponsor within 24 hours 3. Investigator to ethics committee within 7 days
Partners in pharmacovigilance • The WHO quality assurance and safety : medicines team • The uppasala monitoring centre • National pharmacovigilance centres • The pharmaceutical industry • Hospitals and academia • Health professionals • Patients • Others partners
Benefits of monitoring • Improvement in patient care and safety in relation to use of medicines and interventions. • Improvement of public health and safety. • Assessment of benefit, harm, effectiveness and risk of medicines. • Encouragement of safe rational and more cost effective use of medicines • Increase public awareness through communication • Education and clinical training in pharacovigilance • Empowerment and involvement of practitioners, patients and public
How to recognize ADR • Ensure the medicine ordered is the medicine received and actually taken by the patient. • Verify the onset of suspected ADR was after the drug was taken, not before and discuss carefully the observation made by the patient. • Determine the time interval between the beginning of drug treatment and the onset of event. • Evaluate the suspected ADR after discontinuing the drugs or reducing the dose and monitor the patient’s status. If appropriate restart and monitor the recurrence. • Analyze the alternative causes that could on their own have caused the reaction.
Contd. • Use relevant up to date literature and personal experience on the drugs and ADR to verify previous reports on the reaction-through pharmacovigilance center and drug information center. • Report any suspected ADR to the reporting center in the hospital or national ADR center.
Ethics in pharmacovigilance • The Erice declaration provides framework of values and practice for collection, analysis and subsequent communication of drug safety issues. • It asserts scientific and clinical issues on the one hand and right of the public to be openly and fully informed on the other. • It requires the active commitment of all involved regulators, policy makers, health personnel, journalists and (not last) pharmaceutical manufacturers. • Information about drug safety programmes should be easily available to the public so that the central role of patient in safe and rational use of drugs is understood. • Available information is not always reliable and scientifically valid. Direct advertising to the consumer resulting self medication, illicit sale of medicines over internet and over prescribing by doctor on demand.
The Erice Declaration(1997) • Challenges all these players – – – – – – –
Public health administration Health professionals The pharmaceutical industry Government Drug regulators The media Consumers to strive towards the highest ethical, professional and scientific standards in protecting and promoting the safe use of medicines The declaration urges governments and others involved in determining policies relating to the benefit, harm, effectiveness and risk of medicines to account for what they communicate to the public and patients.
Protecting patient confidentiality
Pharmacovigilance in clinical practice
Educational strategies • Integrating pharmacovigilance in UG education • Basic training of health professionals • Training of health workers • Consumer education and information • Drug bulletins to prescribers and consumers • Drug information centers to be established
What is ADR monitoring ? • Systemically collecting information about adverse drug experiences with the aim of, through feed back to the parties involved, contribute to continuously improving drug therapy.
Aim : To detect • Serious unexpected ADRs • Increased or unexpectedly high frequency of known significant ADRs • To prepare list of ADRs not previously reported • To disseminate the information through regular bulletins, reports, and articles in the press
Need for monitoring • Short coming of premarketing studieswhich reveal most common and acute untoward effect • Increase cost of patient care • Medication : 10-57% is self medication • Our country has vast population, poverty and rich research ground • Accelerated approval and rapid introduction of new drugs • Paucity of ADR data
Who reports ? • Doctors-hospital level,MO from PHC,GP’s • Dentists • Drug manufacturers • Pharmacists and nurses
Types of ADR Type
Type of effect
Features
examples
A
Augmented
Common, predictable, low mortality
Bradycardia–βblockers
B
Bizarre
Uncommon, unpredictable, high morbidity & high mortality
Anaphylaxis Penicillin
C
Chronic
Dose related & time related
Dyskinesia Levodopa
D
Delayed
Time Related
Teratogenesis
E
End of use
Withdrawal of chronic therapy abruptly
Corticosteroids
F
Failure
Unexpected failure of therapy
Oral contraceptive failure - Rifampin
What to report ? • New drugs – all suspected adverse reaction • Established drugs - All serious reactions-well recognized - All reactions to vaccines - Unexpected high frequency of a known adverse reaction - All reactions to pregnant & lactating women including new born
Where to report ? • Nearest ADR monitoring centers • Peripheral centers • Regional centers national center at new Delhi • Directly on internet www.fda.gov/MedWatch
Reasons not to report • • • • • • • • • •
Uncertain association Too trivial to report Too well known to report Unaware- existence of national center Unaware- of the need of to report of ADRs Not enough time Non availability of ADR forms Too bureaucratic Legal issues Lack of feed back
Thank you Dr.manjunath
History • 1961 - thalidomide disaster • 1968 – WHO pilot research project for international drug monitoring • 1971 – WHO meeting 1.to advocate establishment of national centers for drug monitoring 2.to provide guidelines 3.to identify the contribution that national centers might take to the international system
Contd. • 1984 – international society of pharmacoepidemiology • 1992 – european society of pharmacovigilance • 2002 – WHO pharmacovigilance • 2004 – national pharmacovigilance advisory committee (NHAC) with DGHS as chairman and drug controller general of india as member secretary • 24 peripheral centers, 6 regional centers and 2 zonal centers
Widening horizons • Illegal sale of medicines and drugs of abuse over internet • Increasing self medication practices • Widespread manufacture and sale of counterfeit and substandard medicines • Increasing use of traditional medicines outside the confines of traditional culture of use • Increasing use medicines of different systems with potential for drug interactions
Post marketing surveillance • Monitoring of drug safety after introducing into the market through various systems • Need 1.To assess risk benefit ratio 2.To confirm safety and efficacy 3.To detect less common adverse effects
Methods of surveillance • Anecdotal reporting • Voluntary reporting • Intensive event reporting • Cohort studies (prospective) • Case control studies (retrospective) • Population statistics • Meta-analysis
Organizations involved • WHO – collaborating center for international drug monitoring is Uppsala monitoring centre provides activities and events in PV • CIOMS – council for international organizations of medical sciences-safety information communication between regulators and industries. • ICH – international conference on harmonization discusses scientific and technical aspects of product registration. • WHO-ART – WHO adverse reaction terminology for coding clinical information to drug therapy.
Frequency of ADR • Very common>=1/10 • Common >=1/100 and <1/10 • Uncommon >=1/1000 and <1/100 • Rare >=1/10000 and <1/1000 • Very rare <1/10000
Causality assessment • Certain : proven on dechallenge and rechallenge • Probable : dechallenge confirms.cannot rechallenge • Possible : can be explained by concurrent disease or other drugs • Unlikely : not documented in literature • Unclassified : additional data is awaited so not documented • Unclassifiable : additional data has come but not fit into any categories
Methods of causality assessment • WHO assessment scale • Naranjo’s scale • European ABO system • Karch and Lasagna’s scale • Kramer scale • Bayesian network • Yale logarithm • Spanish imputation system
question 1
Are there previous conclusion reports on this
Yes
No
+1
0
0
Don’t know
reaction? 2
Did the adverse event appear after the suspect drug was administered?
+2
-1
0
3
Did the AR improve when the drug was discontinued or a specific antagonist was administered?
+1
0
0
4
Did the AR reappear when drug was readministered?
+2
-1
0
5
Are there alternate causes [other than the drug] that -1 could solely have caused the reaction?
+2
0
6
Did the reaction reappear when a placebo was given?
-1
+1
0
7
Was the drug detected in the blood [or other fluids]
+1
0
0
in a concentration known to be toxic? 8
Was the reaction more severe when the dose was increased, or less severe when the dose was decreased?
+1
0
0
9
Did the patient have a similar reaction to the same
+1
0
0
+1
0
0
or similar drugs in any previous exposure? 10
Was the adverse event confirmed by objective
Interpretation • > 9 = definite • 5-8 = probable • 1-4 = possible • 0 = unlikely
Schedule Y requirement • Unsuspected adverse event is communicated from 1.Sponsor to regulatory authorities within 14 days 2. Investigator to sponsor within 24 hours 3. Investigator to ethics committee within 7 days
Partners in pharmacovigilance • The WHO quality assurance and safety : medicines team • The uppasala monitoring centre • National pharmacovigilance centres • The pharmaceutical industry • Hospitals and academia • Health professionals • Patients • Others partners
Benefits of monitoring • Improvement in patient care and safety in relation to use of medicines and interventions. • Improvement of public health and safety. • Assessment of benefit, harm, effectiveness and risk of medicines. • Encouragement of safe rational and more cost effective use of medicines • Increase public awareness through communication • Education and clinical training in pharacovigilance • Empowerment and involvement of practitioners, patients and public
How to recognize ADR • Ensure the medicine ordered is the medicine received and actually taken by the patient. • Verify the onset of suspected ADR was after the drug was taken, not before and discuss carefully the observation made by the patient. • Determine the time interval between the beginning of drug treatment and the onset of event. • Evaluate the suspected ADR after discontinuing the drugs or reducing the dose and monitor the patient’s status. If appropriate restart and monitor the recurrence. • Analyze the alternative causes that could on their own have caused the reaction.
Contd. • Use relevant up to date literature and personal experience on the drugs and ADR to verify previous reports on the reaction-through pharmacovigilance center and drug information center. • Report any suspected ADR to the reporting center in the hospital or national ADR center.
Ethics in pharmacovigilance • The Erice declaration provides framework of values and practice for collection, analysis and subsequent communication of drug safety issues. • It asserts scientific and clinical issues on the one hand and right of the public to be openly and fully informed on the other. • It requires the active commitment of all involved regulators, policy makers, health personnel, journalists and (not last) pharmaceutical manufacturers. • Information about drug safety programmes should be easily available to the public so that the central role of patient in safe and rational use of drugs is understood. • Available information is not always reliable and scientifically valid. Direct advertising to the consumer resulting self medication, illicit sale of medicines over internet and over prescribing by doctor on demand.
The Erice Declaration(1997) • Challenges all these players – – – – – – –
Public health administration Health professionals The pharmaceutical industry Government Drug regulators The media Consumers to strive towards the highest ethical, professional and scientific standards in protecting and promoting the safe use of medicines The declaration urges governments and others involved in determining policies relating to the benefit, harm, effectiveness and risk of medicines to account for what they communicate to the public and patients.
Protecting patient confidentiality
Pharmacovigilance in clinical practice
Educational strategies • Integrating pharmacovigilance in UG education • Basic training of health professionals • Training of health workers • Consumer education and information • Drug bulletins to prescribers and consumers • Drug information centers to be established
What is ADR monitoring ? • Systemically collecting information about adverse drug experiences with the aim of, through feed back to the parties involved, contribute to continuously improving drug therapy.
Aim : To detect • Serious unexpected ADRs • Increased or unexpectedly high frequency of known significant ADRs • To prepare list of ADRs not previously reported • To disseminate the information through regular bulletins, reports, and articles in the press
Need for monitoring • Short coming of premarketing studieswhich reveal most common and acute untoward effect • Increase cost of patient care • Medication : 10-57% is self medication • Our country has vast population, poverty and rich research ground • Accelerated approval and rapid introduction of new drugs • Paucity of ADR data
Who reports ? • Doctors-hospital level,MO from PHC,GP’s • Dentists • Drug manufacturers • Pharmacists and nurses
Types of ADR Type
Type of effect
Features
examples
A
Augmented
Common, predictable, low mortality
Bradycardia–βblockers
B
Bizarre
Uncommon, unpredictable, high morbidity & high mortality
Anaphylaxis Penicillin
C
Chronic
Dose related & time related
Dyskinesia Levodopa
D
Delayed
Time Related
Teratogenesis
E
End of use
Withdrawal of chronic therapy abruptly
Corticosteroids
F
Failure
Unexpected failure of therapy
Oral contraceptive failure - Rifampin
What to report ? • New drugs – all suspected adverse reaction • Established drugs - All serious reactions-well recognized - All reactions to vaccines - Unexpected high frequency of a known adverse reaction - All reactions to pregnant & lactating women including new born
Where to report ? • Nearest ADR monitoring centers • Peripheral centers • Regional centers national center at new Delhi • Directly on internet www.fda.gov/MedWatch
Reasons not to report • • • • • • • • • •
Uncertain association Too trivial to report Too well known to report Unaware- existence of national center Unaware- of the need of to report of ADRs Not enough time Non availability of ADR forms Too bureaucratic Legal issues Lack of feed back
Thank you Dr.manjunath
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