WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

Anusha et al. World Journal of Pharmacy and Pharmaceutical Sciences

SJIF Impact Factor 6.041

Volume 6, Issue 1, 300-310 Review Article ISSN 2278 – 4357

A REVIEW ON PHARMACOVIGILANCE AND ITS IMPORTANCE

I. Lakshmi Anusha*, M. Aashritha, K. Teja and R. Sridhar

Department of Pharmacy Practice, Hindu College of Pharmacy, (A.P), India.

Article Received on
ABSTRACT
15 Nov. 2016, Pharmacovigilance defined by the world health organization as "the
Revised on 05 Dec. 2016,
Accepted on 25 Dec. 2016
science and activities relating to the detection, assessment,
DOI: 10.20959/wjpps20171-8280 understanding, assessment and prevention of adverse effects or any
other drug related problems". It plays a key role in ensuring that

*Corresponding Author patients receive safe drugs. Our knowledge of a drug’s adverse
I. Lakshmi Anusha reactions can be increased by various means, including spontaneous
Department of Pharmacy reporting, intensive monitoring and database studies. New processes
Practice, Hindu College of
both at a regulatory and scientific level are being developed with the
Pharmacy, (A.P), India.
aim of strengthening pharmacovigilance. On a regulatory level,
transparency and increased patient involvement are two important elements.[1]

KEYWORDS: Drug regulation, Drug safety, Intensive monitoring, Pharmacovigilance,

Spontaneous reporting, Transparency.

INTRODUCTION
Pharmacovigilance is the science and activities relating to detection, assessment,
understanding and prevention of adverse effects or any other drug related problems. These
adverse drugs reactions (ADRs) not only add to suffering of patients but also increase
morbidity and mortality along with a financial burden on society. The overall incidence of
ADRs in hospitalized patients is estimated to be 6.7% (range 1.2-24.1%) and that of fatal
ADRs 0.32% (0.1-0.85%).[2] Data indicates that in patients who experience ADRs, death
rates are 19.18% higher and the length of hospital stay is 8.25% higher. Total medical cost
for patients with ADRs are increased by an average of 19.86%.[3] However the lack of ability
of clinicians to suspect or detect such adverse events related to drugs might lead to
inappropriate management of adverse events, thus exposing the patients to additional drug
hazards. To minimize the suffering of the patients from ADRs, though difficult, it is essential
to establish casual relationship between the drug and the event which is the causality

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assessment. By definition, Causality assessment is the evaluation of the likelihood that a

particular treatment is the cause of an observed Adverse Event.[4] It assesses the relationship
between a drug treatment and the occurrence of an adverse even. It is an important
component of pharmacovigilance, contributing to better evaluation of the risk-benefit profiles
of medicines[5] and is an essential part of evaluating ADR reports in early warning systems
and for regulatory purposes.[6]

ADVERSE DRUG REACTION

At a normal dose sometimes the given medications may harm the patients which are called
Adverse Drug Reactions (ADR).[7] Adverse drug reaction is different from side effect. The
evaluation of ADRs is most critical in the field of pharmacovigilance.

Concerning marketed remedies, a suitable definition of an adverse drug reaction is as follows:

1. Unlisted/Unexpected Adverse Drug Reaction
An adverse reaction is the nature or harshness of drug which is not reliable with the proper
product data available at the time of clinical trials.[7]

Company is needed help during investigators brochure for an unapproved drug.

Brief summary of drug data sheet for an official product.

2. Listed / Expected Adverse Drug Reaction

The information about ADR like nature or severity and specificity of the drug is already
recorded.[8]

ADVERSE DRUG REACTIONS REPORTING

When the adverse reaction to drugs is potentially serious or clinically important, all health
care workers including doctors, pharmacists, nurses and other health experts are requested to
clarify it. It is necessary to report an adverse drug reaction to pharmacovigilance.

SPONTANEOUS REPORTING SYSTEM

1. Regionalization
2. Repossession of further data
3. Access to all important pre and post marketing information
4. Detailed drug utilization data.
5. Standardized Evaluation of causality and significance

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6. Encouragement

Documentation of ADRs
The pharmacovigilance curriculum conveyed worldwide motivate that all suspected drug-
related adverse events should be outlined. It takes interests on reports of the following:
(A) Every adverse effect suspected or occurred by new drugs and drugs of current issue
(B) Documentation of various drugs that cause ADRs, which include death, life-threatening
conditions, disability, hospitalization and congenital abnormalities

The significant adverse reaction of any drug should be notified within seven days. The other
facts related to adverse events should be informed within eight days. (Bates et al. 1995:
Classen et al 1997). The ADR form can be collected through any pharmacovigilance centre.
After reviewing the form, the centre forwards it to the regional centre and after that, it is
propelled to the zonal centre (Goldman 1998: Palaian et al. 2006: Ravi Shankar et al. 2010).
The details are then statistically inspected and forwarded to WHO-Uppsala Monitoring
committee (UMC).[9]

PROCEDURE FOR REPORTING ADRs

It is the first duty of any pharmacovigilance centre to report all suspected adverse events of
the drug if found. Information regarding ADRs that should be reported and tabulated.

Elements in ADR reporting Necessary information Others

What should be reported Adverse reaction of drugs Medication over dose, [Link]
Who can report Doctors, Pharmacists, Nurses All government and private hospital
staff
When it can be reported Any adverse reaction if noticed --
How to report Through completely filled yellow form --
Where it can be reported Complete filled ADR form should be
submitted to PVpI. --

Monitoring of ADRs
ADR monitoring is the practice of continuously monitoring the undesirable effects caused
using any drug. Pharmacovigilance plays an imperative impersonation in monitoring
ADRs.[10]

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It is inherent for pharmaceutical regulators to screen their pharmaceutical products in the

market and record if any suspected adverse reactions are identified. ADRs can occur by use
of various pharmaceutical products, herbal drugs, cosmetics, medical devices, biological etc.
Introducing this monitoring procedure intends at warranting that patients to receive safe and
beneficial medicinal products.{Karch and Lasanga 1997}.

If any of the adverse events are not stated, it may result in noxious and serious effects of
remedial products. Thus properly conducting ADR monitoring programs will help to reduce
the harmful effects of therapeutic products.

Benefits of ADR monitoring

An ADR monitoring and reporting program can furnish following benefits:
1. It caters information about quality and safety of pharmaceutical products.
2. It initiates risk-management plans.
3. It prevents the predictable adverse effects and helps in measuring ADR adherence.
4. It instructs health care team i.e., patients, pharmacists and nurses about adverse drug
effects and creates awareness regarding ADRs.

The main objective of ADR monitoring is to disclose the quality and frequency of ADRs and
to identify the risk factors that can cause the adverse reactions.[10]

Serious Adverse Event

A serious adverse event (SAE) in human drug trials are defined as any untoward medical
occurrence that is caused at any dose
(a) Results in death
(b) Is life threatening
(c) Require in-patient hospitalization
(d) Prolongation of existing hospitalization
(e) Causes congenital anomaly/birth defect.[11]
Investigators in human clinical trial are obligated to report these events in clinical study
reports. Research suggests that these events are often inadequately reported in publicly
available reports.[12]

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Pharmacovigilance in India
India has more than half a million qualified doctors and 15,000 hospitals having a bed
strength of 6,24,000. It is the fourth largest producer of pharmaceuticals in the world. It is
emerging as an important trial hub in the world. Many new drugs are introduced in our
country. Therefore, there is a need for a vibrant pharmacovigilance system in the country to
protect the population from the potential harm that may be caused by some of these new
drugs. Clearly aware of the enormity of task the Central Drugs Standard Control Organization
(CDSCO) has initiated a well structured and highly participative National pharmacovigilance
program. It is largely based on the recommendations the WHO document titled "safety
monitoring of medicinal products- Guidelines for setting up and running a pharmacovigilance
centre”.[13]

The specific aims of pharmacovigilance programmers are to:

• Contribute to the regulatory assessment of benefit, harm, effectiveness encouraging their
safe, rational and effective use (including cost effective use).
• Improve patient care and in relation to use medicine and all medical and Para medical
interventions.
• Improve public health and safety in relation to use of medicines
• Promote understanding, education and clinical training in pharmacovigilance and its
effective communication to the public.

Future aspects of pharmacovigilance in India

With more and more clinical trials and other clinical research activities being conducted in
India, there is an immense need to understand the importance of pharmacovigilance and how
it impacts the life cycle of product. Given this situation, the DCGI should act quickly to
improve pharmacovigilance so as to integrate good pharmacovigilance practice in to the
processes and procedures to ensure regulatory compliance and enhance clinical trial safety
and post marketing surveillance. A properly working pharmacovigilance system is essential if
medicines are to be used safely. It will benefit all parties including health care professionals,
regulatory authorities, pharmaceutical companies and the consumers. It helps pharmaceutical
companies to monitor their medicines for risk and to devise and implement effective risk
management plans to save their drugs in difficult circumstances.

The following proposals must be followed

• Building and maintaining a robust pharmacovigilance system

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• Making pharmacovigilance reporting mandatory and introducing pharmacovigilance

inspections
• High-level discussions with various stake holders
• Strengthen the DCGI office with trained scientific and medical assessors for
pharmacovigilance
• Creating a single country specific adverse event reporting form to be used by all
• Creating a clinical trial and post marketing data base for SAEs/ SUSARs / and ADRs for
signal detection and access to all relevant data from various stake holders
• List all new drugs/ indications by maintaining a standard data base for every
pharmaceutical company
• Education and training of medical students, pharmacists and nurses in area of
pharmacovigilance.
• Collaborating with Pharmacovigilance organizations in enhancing drug safety with
advancements in information technology there has been the emergence of new
opportunities for national and international[14]
• Building a network of pharmacovigilance and pharmacoepidemiologists in India.

Developments
• Drug safety information must serve the health of the public.
• Education in the appropriate use of drugs, including interpretation of safety information,
is essential for public at large, as well as for health care providers.
• All the evidence needed to assess and understand risks and benefits must be openly
available.
• Every country needs a system with independent expertise to ensure that safety
information on all available drugs is adequately collected impartially evaluated and made
accessible to all.
• Innovation in drug safety monitoring needs to ensure that emerging problems are
promptly recognized and efficiently deals with and that information and solutions are
effectively communicated.

AIMS OF PHARMACOVIGILANCE
The aims of pharmacovigilance are
• The identification and quantification of previously un-recognized adverse drug reaction
(ADR).

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• The identification of sub-groups of patients at particular risk of ADRs (the risk relating to
dose, age, gender and underlying disease).
• The continued monitoring of a safety of a product, throughout the duration of it use, to
ensure that its risks and benefits remains acceptable. This includes safety monitoring
following significant newly approved indications.
• The comparative adverse drug reaction profile of products within the same therapeutic
class.
• The detection of inappropriate prescription administration.
• The further elucidation of a product pharmacological/toxicological properties and the
mechanism by which it produces adverse drug reactions.
• The detection of significant drug-drug interactions between new products and co-therapy
with agents already established on the market, which may only be detected during
widespread use.[15]

In short, pharmacovigilance aims to improve patient care and safety, public health,
assessment of benefit, harm, effectiveness and risk of medicines promote understanding,
education and clinical training.

IMPORTANCE OF PHARMACOVIGILANCE
When a pharmaceutical drug is introduced in the market there are still a lot of things that are
unknown about the safety of the new drug. These medicines are used by various patients for
different diseases who might be using several other drugs and must be following different
traditions and diets which may adversely affect the impact of medicine in them. Also the
same medicine might differ in the manner of their production and ingredients. Additionally
adverse drug reactions might also occur when drugs are taken along with traditional and
herbal medicines which should be monitored through pharmacovigilance. In some cases,
adverse drug reactions of certain medicine might occur only in one country or region. To
prevent all undue physical, mental and financial suffering of patients, pharmacovigilance
proves to be an important monitoring system for the safety of medicines in a country with the
support of doctors, pharmacists, nurses and other health professionals of the country.[16]
The importance of pharmacovigilance is as follows.
• Safety monitoring of medicinal products
• Clinical trials
• Pharmacoepidemiological studies

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• Case reports
• Developing case series
• Analysis of case series
• Use of data mining to identify product -event combination
• Spontaneous reporting.[16]

STEPS IN PHARMACOVIGILANCE PROGRAMME

1. Finding the risk of a drug
2. Clinical trials
3. Pharmacoepidemiological study
4. Case report
5. Developing case series
6. Analysis of case series
7. Use of data mining to identify product- event combination
8. Spontaneous reporting.

ACTIVITIES IN PHARMACOVIGILANCE OPERATIONS

Case Registry
• Triage
• Registry
• Enrollment

Processing
• Data Entering
• Coding
• Labelling

Medical Review
• Serious Case Medical Review
• Non Serious Listing Review
• Aggregate Report Review

Aggregate Reports
• Analysis And Creation of IND/NDA Reports
• Analysis And Creation of Pader Reports

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• Analysis And Creation of Psur & Bridge Reports

PARTNERS IN PHARMACOVIGILANCE
A complex and vital relationship exists between wide ranges of partners in the practice of
drug safety monitoring. Sustained collaboration and commitment are vital if future challenges
in pharmacovigilance are to be met in order to develop and flourish.
• Government
• Industry
• Hospital and academia[17]
• Poison information centers
• Health professionals[18,19]
• Patients
• Consumers
• Media
• WHO

CONCLUSION
Pharmacovigilance is the only way to ensure the safety of the drug throughout the life cycle.
It is very much crucial as the clinical trials have limitation to detect the rare and very rare
ADRs. The knowledge and information available regarding safety of any drug is very much
important to take appropriate decision by drug regulators to safe guard public health. Health
care professionals are the main reporters of the ADRs. However there are high percentages of
under-reporting reported globally. It is the major challenge of today. In spite of those
limitations, spontaneous reporting system remains as a most widely used method to report
ADRs and is able to generate signal of rare and very rare types of ADRs. If all the health care
professionals take ADR reporting as an ethical obligation and a major responsibility, we can
make our world safer than what is today. Every reporting by health care professionals is
important, even though focus on the serious unlabelled types of ADRs is more important.
There are significant effects on the pharmacovigilance to make it more functional after the
concept has emerged and day by day we are getting closer to the destiny. It is our
responsibility to ensure well functioning of pharmacovigilance system. ADR reporting should
be taken as a very important duty not as an extra clinical burden by health care professionals
to ensure the safer drugs use throughout the world.

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