3. INTRODUCTION
Phases of clinical trial
• Microdosing study ( Phase 0) :Done in very small number of people. Investigators use a very
small dose of medication to make sure that it isn’t harmful to humans before they start
using higher doses for lateral phase.
1.PHASE 1: Healthy volunteers (20-100) Safety & dosage.
2.PHASE2 : People with disease condition (100-300) Efficacy
&side effects.
3.PHASE 3: People with disease condition (300-3000) Confirm
effectiveness and monitoring of adverse drug reaction .
4.PHASE 4(POST MARKETING
SURVEILLANCE ):Track adverse events and monitors
effects in real world.
4. • Postmarketing drug surveillance refers to the monitoring of drugs once they
reach the market after clinical trials.
• It evaluates drugs taken by individuals under a wide range of circumstances
over an extended period of time. Such surveillance is much more likely to
detect previously unrecognized positive or negative effects that may be
associated with a drug.
• The majority of postmarketing surveillance concern adverse drug reactions
(ADRs) monitoring and evaluation.
• Other important postmarketing surveillance components include
unapproved or off-label drug use, problems with orphan drugs, and lack of
paediatric formulations, as well as issues concerning international clinical
trials in paediatric population.
5. • The process of evaluating and improving the
safety of medicines used in paediatric
practice is referred to as paediatric
pharmacovigilance.
It requires special attention. Childhood
diseases and disorders may be qualitatively
and quantitatively different from their adult
equivalents.
6. HISTORY
• Thalidomide was a widely used drug in the late 1950s and early 1960s for
the treatment of nausea in pregnant women.
• In 1961 in Germany ,an astute pediatrition (Lenz) expressed concern about
the sudden large increase in the number of children referred to his clinic
with limb deformitis (Phocomelia) and thalidomide tragedy has been
identified .
• The prevention of unwanted drug effects became matter of worldwide public
concern.
7. • Edward Kennedy (senator) suggested that a better system was needed for
monitoring the use and effects of prescription drugs after they were
marketed.
• As a result, the Joint Commission on Prescription Drug Use was established
in 1976, funded largely by the drug industry, with the mandate to design a
postmarketing surveillance
8. Importance of PMS
• Post market surveillance not only meets regulatory requirements while
monitoring the safety of consumers, but also ensures continuous
consumer acceptance of the products and financial viability.
• Post-market surveillance is a passive, multifactorial, performance-
process for health professionals, manufacturers, regulators and the
monitor the performance during the lifecycle of a product in the open
market.
• It is important for manufacturers and regulators to share common
safety surveillance keeping consumers in mind.
9. Goal of PMS
• The goal of surveillance system is to identify the product use patterns or
conditions responsible for adverse effects and characterize relative incidence
rates compared to market penetration, units sold or other denominator-
generating benchmarking data.
• To determine the frequency of adverse reactions or safety attributable to a
product, spontaneous reports, information on utilization and extent of
consumption is essential.
• Compare a new products or treatments with existing options and the standard of
care .
• Update clinical guidelines as certain populations or groups find more benefit than
others .
10. Benefits of PMS
• Real world evidence delivered through PMS .
• Post-market surveillance can provide additional information on the natural
history of disease and the relative performance of their product to the
disease, as well as other marketed products.
• Post-market surveillance can provide information on how products perform
others in the context of real-world patient populations, which are often
from clinical trial populations. This can then inform treatment decisions,
use of products
• Post-market surveillance can shed light on which products and drugs are
most cost-effective.
11. Types & source of real world data
A.Clinical data : 1)Electronic health records.2)Case report forms.
B. Patient generated data :1) Health & treatment history. 2)Patient reported
outcomes .
C. Cost & utilization data :Claims datasets .
D.Public health data: Government data source
12. Post Market Surveillance System
Evaluate
Report
Collect
Proative data Reactive data
PLAN
PMS PMCF
13. ACTION
• CAPA
Corrective Action :The action was taken to
rectify ,fix or correct a specific deviation ,defect or
undesirable situation .
Preventive Action :The action was taken to
eliminate the cause of deviation ,defect in order
to prevent the future occurrence of such an event
.
• UPDATE:The dosage strength or composition
of dosage form.
14. Process of PMS
Data Collection
• Collect real-
world
data efficiently,
securely, and
accurately for
post-market
surveillance
activities.
Data Analysis
• Use advanced
data science to
transform RWD
to RWE
Data Interpretation
• Once collection
& analysis is
finished,then
interpret the
data easily &
readily.
• To ensure timely
and accurate
interpretation of
data, you need
statistically-
adjusted reports
that are
available in real-
time.
15. Methods of PMS
• The essence of the various methods of postmarketing surveillance of drugs
is the ability to make observations about drug effects in an environment
where the drugs are being used in a customary therapeutic or diagnostic
situation.
• In order to accomplish this, the investigation of marketed drugs requires the
application of observational rather than experimental methods.
• The ability of a particular surveillance method to detect a drug’s effect
depends on two factors.
1) )The time that transpires between use of that drug and the occurrence of
the drug’s effect (the latency period).
2) How often the effect occurs (its frequency).
17. Voluntary Reporting
• Voluntary reporting by physicians and other health care providers, hospitals,
and consumers may act to alert FDA and pharmaceutical firms to possible
adverse effects of drugs.
• These surveillance systems enable physicians and pharmacists to report suspected
ADRs and thus act as a tool to identify new ADRs and risk factors predisposing to
recognized ADRs.
• It is acknowledged that only a small proportion of ADRs are actually reported to
national reporting centres and pharmaceutical companies. Insight into reasons for
underreporting should enable national reporting centres to take appropriate
measures to increase reporting rates.
18. Control clinical trials
• Controlled clinical trials are used primarily for evaluating drug efficacy, not
safety, because they are carried out on hundreds, or, at the most, a few thousand
drug users.
• Their use for evaluating drugs already on the market is also limited by their high
cost and logistical problems.
• These limitations of controlled clinical trials in evaluating the safety of marketed
drugs have led to relying on cohort and case-control methods for postmarketing
studies.
19. Cohort study
• Cohort design is a type of nonexperimental or observational study design.
Cohort studies are important in research design.
• The term “cohort” is derived from the Latin word “Cohors” – “a group of
soldiers.”
• In a cohort study, the participants do not have the outcome of interest to begin
with. They are selected based on the exposure status of the individual. Thus,
some of the participants may have the exposure and others do not have the
exposure at the time of initiation of the study.
• They are then followed over time to evaluate for the occurrence of the
outcome of interest.
20. Prospective
Prospective means looking forward
(into the future)
It is a type of cohort study where the
researchers enrol participants into the study
before they develop the disease.
Involves a group of people who don’t have
the disease under study.
Retrospective
Retrospective means looking
backwards (into the past)
It is a cohort study that analyzes two group of
people those with disease under study as well as a
very similar group of people who do not have the
disease.
Involves a group of people who already
have the disease under study
22. Case control study
• Case-control studies are retrospective.
• They clearly define two groups at the start: one with the disease and
disease.
• They look back to assess whether there is a statistically significant
rates of exposure to a defined risk factor between the groups.
23. Advantages
• Cheaper
• Quicker
• Good for diseases with long latency periods
Disadvantages
• Retrospective / more prone to bias.
• Can only assess one Disease.
