Pharmacovigilance (PV) is defined as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem. WHO established its Programme for International Drug Monitoring in response to the thalidomide disaster detected in 1961. Together with the WHO Collaborating Centre for International Drug Monitoring, Uppsala, WHO promotes PV at the country level. At the end of 2010, 134 countries were part of the WHO PV Programme. The aims of PV are to enhance patient care and patient safety in relation to the use of medicines; and to support public health programmes by providing reliable, balanced information for the effective assessment of the risk-benefit profile of medicines.
2. INTRODUCTION:
History:
• Pharmacovigilance (PV) was officially introduced in December 1961 with the
publication of a letter (case report) in the Lancet by W. McBride, the Australian
doctor who first suspected a causal link between serious fetal deformities
(phocomelia) and thalidomide, a drug used during pregnancy: Thalidomide was
used as an antiemetic and sedative agent in pregnant women.
• In 1968, the World Health Organization (WHO) promoted the “Program for
International Drug Monitoring”, a pilot project aimed to centralize world data
on adverse drug reactions (ADRs). In particular, the main aim of the “WHO
Program” was to identify the earliest possible PV signals.
• The term PV was proposed in the mid-70s by a French group of
pharmacologists and toxicologists to define the activities promoting “The
assessment of the risks of side effects potentially associated with drug
treatment”.
3. What is Pharmacovigilance?
• Pharmacovigilance is the science of collecting, monitoring, researching, assessing
and evaluating information from healthcare providers and patients on the adverse
effects of medications, biological products, blood products, herbals, vaccines,
medical device, traditional and complementary medicines with a view to
identifying new information about hazards associated with products and
preventing harm to patients.
• The challenge of maximizing drug safety and maintaining public confidence has
become increasingly complex.
• Pharmaceutical and biotechnology companies must not only monitor, but also
proactively estimate and manage drug risk throughout a product’s lifecycle, from
development to post-market.
• Three areas of Pharmacovigilance include:
1. Product quality
2. Adverse drug reaction
3. Medication errors
4. • PV is particularly concerned with ADRs, which are drug responses that are
noxious and unintended, and which occur at doses normally used for the
prophylaxis, diagnosis or therapy of disease, or for the modification of
physiological function.
• Continuous monitoring of drug effects, side effects, contraindications and outright
harmful effects which could result in a high degree of morbidity, and in some
cases, even mortality, are essential to maximize benefits and minimize risks.
• Post marketing PV uses tools such as data mining and investigation of case reports
to identify the relationships between drugs and ADRs.
• A complex and vital relationship exists between wide ranges of partners in the
practice of drug safety monitoring such as government, industry, health care
centers, hospitals, academia, medical and pharmaceutical associations, poisons
information centers, health professionals, patients, consumers and media.
Sustained collaboration and commitment are vital if future challenges in PV are to
be met in order to develop and flourish.
5. PHARMACOVIGILANCE IN INDIA:
• The Pharmacovigilance Program of India (PvPI) was launched with a broad
objective to safe guard the health of 1.27 billion people of India.
• Adverse drug Reactions (ADRs) are reported from all over the country to NCC-
PvPI, which also work in collaboration with the global ADR monitoring centre
(WHO-UMC), Sweden to contribute in the global ADRs data base.
• NCC-PvPI monitors the ADRs among Indian population and helps the regulatory
authority of India (CDSCO) in taking decision for safe use of medicines.
• The Central Drugs Standard Control Organisation (CDSCO), New Delhi, under
the aegis of Ministry of Health & Family Welfare, Government of India has
initiated a nation-wide pharmacovigilance programme in July, 2010, with the All
India Institute of Medical Sciences (AIIMS), New Delhi as the National
Coordinating Centre (NCC) for monitoring Adverse Drug Reactions (ADR) in the
country to safe-guard Public Health.
6. • In year 2010, 22 ADR monitoring centres (AMCs) including AIIMS, New Delhi had been
set up under this Programme.
• To ensure implementation of this programme in a more effective way, the National
Coordinating Centre was then shifted from the All India Institute of Medical Sciences
(AIIMS), New Delhi to the Indian Pharmacopoeia Commission (IPC), Ghaziabad, (U.P.)
in April, 2011.
• Healthcare professionals, patients/consumers are advised to closely monitor the
possibility of above adverse events while prescribing /consuming above suspected drugs
and report to the NCC-PvPI either by filling of Suspected Adverse Drug Reactions
Reporting Form/Medicines Side-Effect Reporting Form for
Consumer (http://www.ipc.gov.in) or via PvPI Helpline No. 1800-180-3024.
• The information collected during the pre-marketing phase of a medical drug is
inevitably incomplete with regard to possible adverse reactions:
1. Tests in animals are insufficiently predictive of human safety.
2. Patients in clinical trials are selected and limited in number, the conditions of use
differ from those in clinical practice and the duration of trials is limited.
3. Information about rare but serious adverse reactions, chronic toxicity, and use in
special groups (such as children, the elderly or pregnant women) or drug
interactions is often incomplete or not available.
7. MAJOR AIMS OF PHARMACOVIGILANCE:
• The mission of PvPI is to safeguard the health of the Indian population by ensuring that the benefit of use
of medicine outweighs the risks associated with its use.
• The broadened patient safety scope of pharmacovigilance includes the detection of medicines of
substandard quality as well as prescribing, dispensing and administration errors.
Scope and Objectives:
• To create a nation-wide system for patient safety reporting.
• To identify and analyze new signal from the reported cases.
• To analyze the benefit - risk ratio of marketed medications.
• To generate evidence based information on safety of medicines.
• To support regulatory agencies in the decision-making process on use of medications.
• To communicate the safety information on use of medicines to various stakeholders to minimize the risk.
• To collaborate with other national centers for the exchange of information and data management.
• To provide training and consultancy support to other national pharmacovigilance centers across globe.
• To promote rational use of medicine.
8. DESIGNING A PHARMACOVIGILANCE SYSTEM:
• A country’s pharmacovigilance system should incorporate activities and resources
at the facility, national, and international levels and foster collaboration among a
wide range of partners and organizations that contribute to ensuring medicine
safety.
• Illustrates the components of a comprehensive, ongoing pharmacovigilance
system with functions for monitoring, detecting, reporting, evaluating, and
documenting medicine safety data as well as intervening and gathering
information from and providing educational feedback to the reporters—
prescribers, health care workers, other health care professionals, and consumers.
• When the information has been collected, evaluators, such as epidemiologists or
pharmacologists, should analyze it to determine the adverse event’s severity,
probable causality, and preventability.
• Significant data must be communicated effectively to a structure or entity that has
the authority to take appropriate action, whether at the facility, national, or even
international level.
10. • The outcome of a pharmacovigilance system should be decreased medicine-related
problems with the ultimate effect being a reduction in morbidity and mortality.
The pharmacovigilance framework is shown below:
12. DATA COLLECTION TOOLS:
• ADR and medication error data are
usually collected by filling out a
standardized form, thereby providing
convenience and consistency.
• Data collection tools should be
adapted from standards of practice
and procedures, and the data fields on
the form determined by how the data
are eventually summarized and used.
• For ADR data, identifying specifics
about the patient is important. These
include concomitant therapies and
conditions, the patient’s reaction to
the medicine, and the medicine
suspected of causing the reaction
together with the manufacturer and
batch number, if available. WHO
gives guidance on what to include on
a data collection form.
Fig. ADR reporting form
13. DATAANALYSIS AND REPORTING:
• After the ADR data have been collected, they should be analyzed to determine severity, probable causality, and prevent-ability.
Specific algorithms and classification systems have been developed for these analyses—
• Severity (impact on the patient’s health): It addresses both ADEs associated with medication error and those not associated with
error, so it can be applied to all medication events.
• Probable causality (likelihood that the medicine’s use or lack of use contributed to the ADR): Whether a particular medicine
was actually related to the ADR or not.
• Preventability (Was an error associated with the event?): If the ADE was caused by a medication prescribing error, and
therefore, preventable. Determining whether a medication error occurred:
• Was the drug involved appropriate for the patient’s clinical condition? (NO = Preventable)
• Was the dose, route, or frequency of administration appropriate for the patient’s age, weight, or disease state?
(NO = Preventable)
• Was required therapeutic pharmaceutical monitoring or other necessary laboratory tests performed?
(NO = Preventable)
• Was there a history of allergy or previous events to the drug? (YES = Preventable)
• Was an interaction (medicine–medicine; medicine–food; medicine–herbal) involved in the ADR?
(YES = Preventable)
• Was a toxic serum drug concentration (or laboratory monitoring test) documented?
(YES = Preventable)
• Was poor compliance involved in the ADR? (YES = Preventable)
• Was the error considered preventable because of deviations in procedures or standards of practice?
(Yes = Preventable)
14. • For ADEs that are considered preventable, identifying where the primary error
occurred and what aspects contributed to the system breakdown is useful;
therefore, analysis and reporting should facilitate this activity by identifying and
targeting problem-prone areas, such as specific steps in the process (prescribing
practices), medication types (injectables), disease states or patient types,
employees (new employees, interns), patient care areas (surgery), and time of the
day (night shift).
• Medication event data are organized on manual or electronic spreadsheets, which
help summarize and sort data for reporting at the facility or regional level.
National and international programs often use Internet-based ADR or medication
error databases to collect and share data.
• Reporting the results of ADR and medical error analysis to the organizational
body within a hospital or facility that has responsibility for medicine safety, such
as the drug and therapeutics committee, is also important.
15. CASE STUDY:
• Reporting Form:
The NCC has designed a Suspected Adverse Drug Reaction Reporting Form to record adverse reactions related to
drugs. Separate forms are available to record adverse reactions associated with transfusion of blood and blood products and
Adverse Event Following Immunization. A report that contains information describing a suspected adverse drug reaction
related to the administration of one or more medicinal products to an individual patient is termed as individual case safety
report. An ICSR must contain information on the following items:
A. Patient Information:
1. Patient initials: A reporter should only write the initials of a patient instead of full name. For e.g.: Madhu Gupta should be
written as MG
2. Age at time of event or date of birth: A reporter must report either the date of birth or age of the patient at the time event or
reaction occurred
3. Sex: A reporter must mention the gender of the patient.
4. Weight: The weight of the patient should be in kilograms
B. Suspected Adverse Reaction:
5. Date of reaction started: A reporter must report the date on which the reaction first observed.
6. Date of recovery: If the reaction recovered, the date on which the reaction recovered should be report.
7. Describe reaction: A reporter must describe the event in terms of nature, localization etc. For e.g.: patient developed
erythematous maculopapular rash over upper and lower limp.
16. C. Suspected Medications
8. The details of suspected medication(s) such as drug name (brand or generic name), manufacturer, batch no/lot
no, expiry date, dose used, route used, frequency, dates of therapy started and stopped, and indication of use
must be provided by the reporter.
9. De-challenge details: A reporter must report the status on de-challenge as:
‘Yes’- if reaction abated after de-challenge
‘No’- if reaction does not abated after de-challenge
‘Unknown’- if information on de-challenge is not confirmed
‘Not Applicable’ or ‘NA’- if de-challenge is not applicable as in case of vaccines, anaesthesia or where single
dose is given
‘Reduced dose’- If dose at which the reaction occurred is reduced. Note: Also mention the reduced dose
10. Re-challenge details: A reporter must report the status on re-challenge as:
‘Yes’- if reaction reappeared after re-challenge
‘No’- if reaction does not reappeared after re-challenge
‘Unknown’- if information on re-challenge is not confirmed
‘Not Applicable’ or ‘NA’- if re-challenge is not applicable as in case of injections.
‘Re-introduced dose’- If the reduced dose is increased to dose at which adverse event occurred
11. Concomitant drugs: A reporter should include all the details of concomitant drugs including self-medication,
OTC medication, herbal remedies with therapy dates
12. Relevant tests/ laboratory data: The reporter must report any laboratory data (if available) relevant to the
event occurred.
17. 13. Other relevant history: A reporter must mention any relevant history persistent to patient including pre-existing medical
conditions (e.g. allergies, pregnancy, smoking, alcohol use, hepatic/renal dysfunction).
14. Seriousness of the reaction: If any event is serious in nature, a reporter must tick the appropriate reason for seriousness as:
‘Death’- if the patient died due to adverse event
‘Life-threatening’- if patient was at substantial risk of dying at the time of the adverse event
‘Hospitalisation/prolonged’- if the adverse event cause hospitalisation or increased the hospital stay of the patient
‘Disability’- if adverse event resulted in a substantial disruption of a person's ability to conduct normal life functions
‘Congenital anomaly’- if exposure of drug prior to conception or during pregnancy may have resulted in an adverse outcome in
the child.
‘Required intervention to prevent permanent impairment/damage’- if medical or surgical intervention was necessary to
preclude permanent impairment of a body function, or prevent permanent damage to a body structure
‘Other’ -when the event does not fit the other outcomes, but the event may put the patient at risk and may require medical or
surgical intervention to prevent one of the other outcomes. Examples include serious blood dyscrasias (blood disorders) or
seizures/convulsions that do not result in hospitalization, development of drug dependence or drug abuse
15. Outcomes: The reporter must tick the outcome of the event as:
‘Fatal’- if the patient dies due to adverse event
‘Continuing’- if the patient is continuing with the event occurred
‘Recovering’- if the patient is recovering from the existing event occurred
‘Recovered’- if the patient is recovered from the event occurred
‘Unknown’- if the outcome is not known
18. • D. Reporter
• 16. Name and Professional address: A reporter must mention his/her name and
professional address on the form. The identity of the reporter will be maintained
confidential
• 17. Causality assessment: The reporter (if trained) must perform the causality
assessment.
• 18. Date of report: A reporter must mention the date on which he/she reported the
adverse event.
• For quality reporting of ICSRs all the above mentioned fields are essential. In case
of incomplete information, the reporter must take care that at least mandatory
fields are present.
• Following are the mandatory fields for a valid case report:
• Patient information: initials, age at onset of reaction, gender.
• Suspected adverse reaction: A reaction term(s), date of onset of reaction
• Suspected medication: Drug(s) name, dose, date of therapy started, indication of
use, seriousness, outcome, de-challenge and re-challenge details
• Reporter: Name and address, causality assessment, date of report
19. CONCLUSION:
• Adverse reactions of drugs continue to remain as an important public health issue.
• Safety monitoring of medicines is the responsibility of all stakeholders of the
healthcare system since globally it continues to be an important cause of morbidity
and mortality.
• In some countries adverse drug reactions are among the ten leading causes of
mortality. The safety of patients and the safe use of medicines are crucial for
health policy development and delivery of the best healthcare.
• To prevent or reduce harm to patients thereby improving public health, the safety
of medicines in clinical use must be monitored and evaluated through specialized
systems. This requires a need to establish a well-organized pharmacovigilance
system.
• Pharmacovigilance can help minimize the harm by ensuring that medicines of
good quality are used rationally and that the expectations and concerns of the
patient are taken into account when health care providers are making decisions
about therapy.
