This document discusses pharmacovigilance and post-marketing drug safety monitoring. It defines key terms like adverse drug reaction and signal. It explains limitations of pre-approval clinical trials in detecting all ADRs. Various pharmacovigilance strategies are outlined like spontaneous reporting, prescription event monitoring, and case studies. Reporting procedures and timelines are provided. The national pharmacovigilance program in India is described with its structure and operations. Benefits and limitations of spontaneous reporting are highlighted. Prescription event monitoring is explained as a form of post-marketing surveillance.

1. Dr. Rajesh Hadia
Assistant Professor,
Department of Pharmacy Practice,
SumandeepVidyapeeth Deemed to be University,Vadodara.

2.  Proactive monitoring and reporting on the quality, safety
and efficacy of drugs
 Assessment of risks and benefits of marketed medicines
 Monitoring impact of any corrective actions taken
 Providing information regarding effective use of drugs
 Designing programs and procedures for collecting and
analyzing reports from patients and clinicians

3.  ADR
 A response to a drug which is noxious and unintended
and which occurs at doses normally used in man for
prophylaxis, diagnosis, or therapy of disease or for
modification of physiological function.
 Signal
 Reported information on a possible causal relationship
between an adverse event and a drug, the relationship
being unknown or incompletely documented previously.

4.  Inadequate data provided by Phase I through
III of RCT’s
 Why is the information limited?

5.  Animal studies insufficient to predict human safety.
 Limited number of patients & controlled environment
in RCTs
 Only the more common ADR detected
 Incomplete information about
1. Rare but serious adverse reactions
2. Chronic toxicity
3. Use in special groups
4. Drug interactions
5. Delayed reaction

6. PHARMACOVIGILANCE
STRATEGIES
Drug ADR detected
1. Post-marketing surveillance Felbamate Hepatotoxicity
2. Intensive in-patient monitoring Ampicillin Skin rash
3. Spontaneous ADR monitoring Zimeldine Guillan-Barre syndrome
4. Prescription event monitoring ACE inhibitors Cough
5. Multipurpose database Isotretinoin
Thiazides
Birth defects
6. Case reports / Case series Thalidomide Birth defects
7. Case control studies Various drugs Agranulocytosis,Cancers
8. Cohort studies Oral contraceptives Thromboembolism
9. Randomized controlled trials SSRIs Weight gain

7. It involves identification of and informing the
pharmacovigilance bodies of anADR or an ADE by
medical professionals (physicians, dentists, nursed,
pharmacists)

8.  What to report?
 What all to include?
 Time frame in which to report?
 Where to report?
 Who is to be informed?

9.  ALL adverse events suspected to have been caused by new
drugs and ‘Drugs of current interest' (List to be published
by CDSCO from time to time)
 ALL suspected drug interactions
 Reactions to any other drugs which are suspected of
significantly affecting a patient's management, including
reactions suspected of causing:
 Death
 Life-threatening (real risk of dying)
 Hospitalisation (initial or prolonged)
 Disability (significant, persistent or permanent)
 Congenital anomaly
 Required intervention to prevent permanent impairment or
damage

10.  Karch and Lasagna causality assessment criteria
 Naranjo’s Causality assessment scale
 WHO’s probability scale
 Severity of an ADR
 Predictability
 Preventability

11. 1. Description of event, including time to onset.
2. Suspected & concomitant therapy details.
3. Patient characteristics.
4. Documentation of the diagnosis , including methods used
to make the diagnosis.
5. Clinical course of the event and patient outcomes.
6. Relevant therapeutic measures.
7. Response to dechallenge and rechallenge.
8. Any other relevant information.

12.  Fatal or Life-Threatening Unexpected ADRs:
 As soon as possible / within 7 days of the knowledge of
the ADR
 All Other Serious, Unexpected ADRs
 As soon as possible / Within 15 days of the first
knowledge of the ADR.

13.  CDSCO form
 JIPMER
 www.pharmacovigilance.co.in

14. • Seth G S Medical college &KEM Hospital,
Parel, Mumbai
• AIIMS, Ansari Nagar, New Delhi
2
Zonal Centres
• Kolkatta
• Mumbai
• Nagpur
• New Delhi
• Pondichery
5
Regional
Centres
24
Peripheral
Centres
National Pharmacovigilance Program (NPP), INDIA

15.  1968 WHO Programme International ADR terminology and
drug dictionary was established.
 1969 Definition of ADR
 1978 Operations transferred to the UMC, Sweden; setting-
up of relational ADR database. Regular WHO Programme
member meetings
 India joined the Uppsala Monitoring centre in 1997

16. PROS
 Easy to implement
 Cheap
 Covers all medicines
 Rare & New reactions
identifiable
 Quantification and
characterization of known
hazards
 Identification of drugs as
epidemiologic risk factors
CONS
 Under reporting
 Difficulty in causality
assessment
 Incomplete
 Bias
 Delayed effects unnoticed
 Common clinical problems
not linked to drug

17.  What is PEM?
PEM is a non-interventional, observational cohort form of
pharmacovigilance.
 In PEM, the exposure data are national in scope
throughout the collection period and unaffected by the
kind of selection and exclusion criteria that characterise
clinical trials data.

18.  New drug licence, DSRU decides whether to monitor drug
 PPA notified, all prescriptions issued are identified, Details
of patients and prescribing GPs sent to DSRU
 Green forms sent to GPs
 Green forms returned to DSRU
 Data entered onto computer
 Pregnancies, causes of deaths, serious possible ADRs and
events of interest followed-up
 Confidentiality and security carefully maintained

21.  Drugs to be included in the system are wide-
spread, general practitioner use.
 Outcome data is derived from the green
forms completed by these GPs
 Interim analysis every 2500 patients

22.  Incidence density
 IDt = No of events during treatment for period ‘t’ *1000
No of patient-months of treatment for period ‘t’
Numerator: No of reports
Denominator: No of patient-weeks of exposure
 The incidence density is the measure of the number of
reports of each event per thousand patient months of
exposure to the drug.
 ODD’s Ratio

23.  Only 50 % response rates with green forms
 Loratadine and fexofenadine resulted in a
significantly lower incidence of sedation than
cetirizine and acrivastine

24.  Calculation of incidence density
 Carried out on a national scale
 Comparison of ‘reasons for withdrawal’ and incidence
density
 Outcome of exposed pregnancies
 Signal generation and exploration
 Delayed reactions can be detected
 Disease investigation

25.  No method of measuring compliance
 No method to determine the non-prescription
medication
 Non-return of green forms
 Does not extend to hospital monitoring
 Data collection is an operational difficulty