Why and how to conduct and report drug safety surveillance.

1. 1

2.  What is pharmacovigilance?
 Why is it necessary?
 When should to report?
 Who should do it?
 How it is conducted?
 CONCLUSION.
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3.  WHO defines pharmacovigilance as the science
and activities relating to the detection,
assessment, understanding and prevention of
adverse effects/ adverse drug reaction (ADR) or
any other medicine-related problem.
 Is the study of safety of marketed drugs under the
practical conditions of clinical use in large
populations.
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4.  To improve safety and rational use of medicine
and devices thereby improving patient care and
public health.
 When a medicine is released into the market ,
there is a lot to be learned about it’s safety and
efficacy.
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5.  Pharmacovigilance helps assess risk vs. benefits.
 This information will prevent unnecessary
suffering.
 Decrease financial loss sustained by patients
using inappropriate and unsafe drugs.
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6.  Identify- unknown adverse reactions.
 Evaluate- the balance between benefit vs. risk.
 Provide- optimal information to the users.
 Take Action- to promote safe use.
 Monitor Impact of the action taken.
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7. MAH
~ Data Source
~Clinical Trials/CRO
Regulatory
Body
HCP Others (Lawyers)
~Patients ~Patients
~Lit review ~Data Source
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8.  Pharmacovigilance should be done
during:
 clinical trials.
 post marketing surveillance (PMS).
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9.  Report Severe Adverse Events (SAE) and
unexpected adverse to the sponsor within 24hrs
and to the ethics committee within 7 days.
 Safety Adverse Report should be received by the
FDA within 14days.
 EU requirements for PMS;
~first 2 years after authorization report every
6months.
~next 2 years, report once a year.
~after that report every 3 year.
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10.  FDA
 Center for Drug Evaluation and Research
(CDER)
 IRB/ Ethics committee
 EU (EMEA, MHRA)
 MHLW ~ Japan
 CDSCO~ India
 WHO ~UPPSLA
 Others.
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11.  A reaction or response to medicine which is
noxious or unintended, including lack of
efficacy.
 Can occur at any dosage resulting from
overdose, misuse or abuse of medication.
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12.  Name of drug/device.
 All suspected ADRs.
 Lack of efficacy and suspected defects on the device.
 Counterfeit medicines.
 Development of resistance e.g. antibiotics.
 Overdose, misuse.
 Medical error.
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13.  Outcome of use during pregnancy.
 Adverse reaction during breastfeeding.
 Data on the pediatrics population.
 Concomitant drugs.
 Comorbidities.
 Age, gender.
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14.  Reporting ofadverse events and medication errors
is done voluntarily :
healthcare professionals (such as physicians,
physician assistants pharmacists, nurses) to the
regulatory bodies and manufacturers.
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15. Manufacturer report to the FDA in a timely
manner.
 ADRs are entered into AERS (Adverse Event
Reporting System) .
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16. Monitor
Collect Identify Evaluate Act on it
impact
 Periodic Safety Data Update (PSUR) is a
regulatory document prepared by the Marketing
Authorization Holder (MAH) and submitted to
the FDA.
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17.  Passive surveillance.
~case series.
~spontaneous case reporting.
 Stimulated reporting.
 Active surveillance.
~ sentinel sites.
~drug event monitoring.
~registries.
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18.  Comparative observational studies.
~cross sectional studies.
~case control study.
~cohort study.
 Targeted clinical investigations.
 Descriptive Studies.
~natural history of disease.
~drug utilization study
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19. Identification
Signal detection of new previously not known side
effect.
Evaluation
 Clinical assessment of ADR’s.
Take Action
 Reporting.
 Creating awareness among. healthcare providers and
the public.
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20.  Fatal, death.
 Life threatening.
 Disability or incapacitation.
 Prolonged hospitalization.
 Congenital abnormality.
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21.  Type A
Pharmacological Mechanism
Common > 1%
Dose relationship
Suggestive time relationship
Reproducible
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22.  Type B
Specific characteristic reaction
Immuno-allergic reactions
Rare reaction <1%
Susceptible to individuals
Not reproducible
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23.  Type C (Chronic)
Due to repeat use of the drug.
Time relationship variable.
Difficult to reproduce.
Mechanism unknown.
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24.  Type D ( Delayed)
 Takes time to develop
 Carcinogenic, tetratogenesis
Type E (Eliminated)
 appears after termination of therapy
 Rebound phenomena
Type F ( Failure)
 therapeutic failure
 Inefficiencies (Vaccines, contraceptives)
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25.  Case report describes suspected adverse reaction.
 Certain ADR
 Probable ADR
 Possible ADR
 Causality unlikely/ unclear ADR
 No ADRs
 Uncertain/unknown
 Un-assessable
 De-challenge and re-challenge test.
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26.  To establish causality or lack of the following is
investigated:
i. Association of time/place between drug use and
event.
ii. Pharmacology including current knowledge,
nature and frequency of adverse reaction.
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27. iii. Medical and pharmacological plausibility
signs and symptoms,
lab tests,
pathological findings.
iv. Likelihood of exclusion of other causes.
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28.  Dechallenge test: when the drug is
discontinued, the reaction resolves.
 ReChallenge test: when the drug is restarted,
the reaction reappears.
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29.  Adverse reaction case reports by MAH.
 PSUR (Periodic Safety Update Report).
 Spontaneous reporting system.
~national PV center/ Drug authorities.
~published scientific literature.
 Drug bulletins.
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30.  Information should be communicated ethically
and effectively to all involved parties.
 Education of proper drug use in crucial with
dissemination of safety information to the public.
 All evidence needed to assess and understand
risk and benefit should be readily available.
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31. Pharmacovigilance reporting:
I. Creates public awareness on drug use.
II. Ensures that risks in drug use are anticipated and
managed.
III. Provides the information required by regulators to amend
drug regimen.
IV. Improves communication between the health industry and
the public.
V. Educates healthcare providers on the risk vs. benefit of
prescriptions.
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32.  Benefit vs. Risk assessment- is key in decision
making.
 Public Health Safety- PMS is important to achieve
safe and rational use of medicines and devices.
 Improvements and changes should be made in a
timely manner.
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33. WHOhttp://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInfo
rmation/Surveillance/AdverseDrugEffects/default.htm
FDAhttp://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInfor
mation/Surveillance/AdverseDrugEffects/ucm115894.htm
WHOhttp://apps.who.int/medicinedocs/en/d/Js6164e/5.html
Wood, Louise; Martinez, Carlos. The General Practice Research
Database: Role in Pharmacovigilance. Drug Safety, Volume 27,
Number 12, 2004 , pp. 871-881(11)
Patrick C. Waller*, Stephen J. W. Evans. A model for the future
conduct of pharmacovigilance. Pharmacoepidemiology and Drug
Safety Volume 12, Issue 1, pages 17–29, Jan/Feb 2003.
Anne Trontell, M.D., M.P.H. Expecting the Unexpected — Drug Safety,
Pharmacovigilance, and the Prepared Mind N Engl J Med 2004;
351:1385-1387Sept 30, 2004
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