Definitions: Drug, PV, AE
Need for PV-Clinical Trails and Post
PV in countries
Benefits- Public and drug manufacturer
Day 1 Overview : POP Quiz
1. Name the drug regulatory body which governs the approval process in India?
CDSCO (central drugs standards and control organization)
2. Which Clinical Trial phase involves giving drug to large group 100-300 people?
3. Which Clinical Trial Phase takes about 3 years to complete?
4. NDA stands for?
New Drug Application
5. What are the 4 stages of drug development process?
Pre-clinical, Clinical, NDA Review, Post-marketing
• Early 20th
century there were no controls over the drug development
• Claims over treating diseases and uncontrolled marketing.
• Safety or effectiveness of the drug- NOT a concern for government.
• 1883 Dr. Harvey Wiley initiated the campaign for Federal law for
Food and Drugs Act that was finally passed in 1906.
• The law was further tightened following incidents such as poisoning
of children by Sulphanilamide and the Thalidomide tragedy.
• 1938 Federal Food, Drug, and Cosmetic Act.
Substance or mixture of substances used for diagnosis,
treatment, mitigation or prevention of disease or disorders.
Used for restoring correcting or modifying organic functions
in human beings or animals.
Clinical Testing – Phase I
Clinical Testing – Phase II
Clinical Testing – Phase III
New Drug Application
Clinical Testing–Phase IV
IB,ICF, AE, Placebo, Blinding, randomized, Serious, Concomitant medication, Causality,
IB- comprehensive document summarizing information about an
investigational product obtained during a drug trial.
critical importance throughout the drug development process and is
updated with new information as it becomes available.
The purpose of the IB is to compile data relevant to studies of the IP in
human subjects gathered during preclinical and other clinical trials.
An IB is intended to provide the investigator with insights necessary for
management of study conduct and study subjects throughout a clinical trial.
An IB may introduce key aspects and safety measures of a clinical trial
protocol, such as:
Dose (of the study drug)
Frequency of dosing interval
Methods of administration
Safety monitoring procedures7
An IB contains a "Summary of Data and Guidance for the Investigator"
section, of which the overall aim is to "provide the investigator with a
clear understanding of the possible risks and adverse reactions, and
of the specific tests, observations, and precautions that may be
needed for a clinical trial.
This understanding should be based on the available physical,
chemical, pharmaceutical, pharmacological, toxicological, and clinical
information on the IP.
Guidance should also be provided to the clinical investigator on the
recognition and treatment of possible overdose and adverse drug
reactions that is based on previous human experience and on the
pharmacology of the investigational product".
•ICF- subject voluntarily confirms to participate, made aware of all aspects
•Placebo- A substance containing no medication, given to reinforce a patient's
expectation to get well (an inactive substance or preparation used as a control
to determine the effectiveness of a medicinal drug) GUIDELINES (declaration
•Blinding/Masking- one or more parties kept unaware of the treatment
•-Single blinding subjects unaware
•-double blinding subjects, investigators, monitor, data analysts are also
•Randomized- subjects assigned randomly to treatment or control ( chance to
•Serious- death, LT, hospitalization, disability, birth defect
•Concomitant medication- medications used by patients in a clinical trial, other
than the investigational drug. ( also to treat AE)
•Causality- that AE was due to the medicine in question
Any unfavorable and unintended sign, symptom or a disease temporarily
associated with the use of medicinal product (drug), whether or not
considered related to the medicinal product.
can be lab finding too or symptom or disease temporally associated with
use of IP, whether or not related to the IP
Need of pharmacovigilance
There is a need to monitor the effects of drugs
during the clinical trials and after its launch in a
Because adverse events can even happen during the
clinical trials and event after its launch market.
pharmakon-a drug or medicine
vigilans-watchful or careful
World health organization (WHO, 2004) defines “pharmacovigilance” as
the science and activities relating to the detection, assessment,
understanding, and prevention of adverse drug reactions (ADRs), or any
other medicine-related problems.
Safety monitoring and evaluation throughout whole life-
cycle of a product
Encompasses non-clinical, clinical, post-marketing
Day:2 Overview: POP QUIZ!
1.When was the Food drug and cosmetic Act passed?
2. When can a case be called Serious?
When the outcome of the event is death, LT, hospitalization, disability, birth
3. In which phase is the likelihood of an adverse event maximum of all the 4 phases?
Trick question!!! All phases of preclinical and clinical.
4. What does IB stand for?
5. What are the uses of Thalidomide?
Initially discovered as an painkiller on soldiers, later used on pregnant women
for its antiemetic use. Also treats leprosy- but banned now.
Anti cancer property exploited by Celgene to treat multiple myeloma marketed
as lenalidomide (less sideeffects)
Why pharmacovigilance in clinical trials
After the completing preclinical studies in
animals, first time trial drug will be
administered to the human.
At this time the drug will act in different
way to the human body.
Chances of adverse will also persist.
Pharmacovigilance in post marketing –
At the time of approval, clinical trial data are available on
limited numbers of patients treated for relatively short periods
Once a product is marketed, large numbers of patients may be
Patients with co-morbid illnesses
Patients using concomitant medications
Patients with chronic exposure
Genetic diversity in large population
The evaluation of risk must be conducted in the context
patient benefit derived from treatment,
the severity of the condition being treated,
and other objective and
subjective factors (such as the patient’s values).
Pharmacovigilance – Why?
After marketing, new safety information may become
Through use of the product domestically or in other countries
Through use of other drugs in the same class
From preclinical studies
From pharmacologic studies
From clinical trials
Importance of Pharmacovigilance in every
There are differences among countries ( and even within countries )
in the occurrence of ADRs (Adverse drug reactions) and other
drug related problems
Differences in diseases
Traditions/lifestyle of people
Drug manufacturing processes
The use of drugs ( dose, indications and availability)
Who reports about adverse events in
Who reports about adverse events in clinical Trials
Who reports in post marketing adverse events
Spontaneous reporting of suspected adverse
drug effects is central to pharmacovigilance—
which is the systematic search for signals of drug
When such a signal is detected it has to be
verified, explored, and understood—realizing that
the drug may be acceptably safe if used by
individuals who are not at especially high risk by
virtue of genetic constitution, metabolism, or other
characteristics that could alter individual risk.
Partners in Pharmacovigilance
Hospitals and academia
Medical and pharmaceutical associations
medicines information centers
World Health Organization
Each of the stakeholders—the patient, physician, pharmaceutical company,
academic investigator, government—may have a different perspective on the
same set of evidence.
• A patient may be willing to accept a high risk of side-effects for benefits of the treatment for a
condition that might be considered trivial by others.
• A regulatory agency may consider the burden of the same side effects to be too high, given
their view of the risk–benefit equation.
• A governmental or third-party payer might see the issue from an even different
perspective, since a payer may not wish to bear the cost of the treatment or the cost of treating an
• It is not surprising that each group may take a different view of the same
• These pressures may lead to early decisions based on incomplete scientific
What is the role of pharmacovigilance?
The goal of pharmacovigilance is to:
Monitor the quality of drugs
Identify the health risks involved in the administration of
Prevent harm to patients
Research the efficacy of drugs
How does pharmacovigilance help the public?
Pharmacovigilance helps save thousands of lives each year. By
monitoring the adverse effects of drugs right from the lab to the
pharmacy and then on for many years, pharmacovigilance keeps
track of any drastic effects of drugs. This way, it prevents harm
to patients using those drugs.
How does pharmacovigilance help drug
Pharmaceutical companies spend millions of dollars and a considerably
long-time in developing new drugs. They again spend a lot of money
in conducting clinical trials before the drugs are approved and
launched in the market. But after all this, if there are adverse effects to
the drugs, the company again loses millions of dollars in sales and
Furthermore, the reputation of the company is also severely damaged.
Pharmacovigilance monitors the development of the drug across
various stages and assesses its effectiveness after its launch for many
years. This way it may reduce the adverse risk from drugs, thereby
aiding the drug manufacturers.
Regulatory agencies are increasingly proactive in seeking out
potential safety issues with marketed drugs - you must be ready
to respond quickly
Political and social pressures have increased along with faster
Failure to practice pharmacovigilance can lead to the suspension
or withdrawal of license
Rationale for pharmacovigilance
Builds up customer confidence
Ensures Compliance and retention
Builds brand image
Rationale for pharmacovigilance
What to report?
ADR associated vaccines, diagnostics, drugs used in
traditional medicine, herbal remedies, cosmetics, medical
devices and equipment
lack of efficacy and suspected pharmaceutical defects
overdose (because may cast doubt on safety of a drug)
Rationale for pharmacovigilance
What to report?
Every single problem related to the use of a drug, because
probably nobody else is collecting such information!
NOTE: When in doubt- Always report!!