Post-marketing surveillance (PMS) monitors drug and medical device safety after market release using approaches like spontaneous reporting databases, prescription monitoring, and health records. PMS identifies potential safety issues through data review and helps detect rare or long-term adverse effects not seen in pre-market clinical trials which have limited patient populations and durations. PMS provides additional safety and efficacy information on marketed products and allows monitoring of special patient groups. Common PMS methods include spontaneous reporting, observational studies, randomized trials, and active surveillance networks.

1. Presented by,
ARATHY R NATH

2. INTRODUCTION
Post marketing surveillance (PMS) (also post
market surveillance) is the practice of
monitoring the safety of a pharmaceutical
drug or medical device after it has been
released on the market
It is an important part of the science
of pharmacovigilance

3. Post marketing surveillance uses a number of
approaches to monitor drug and device safety,
including :-
spontaneous reporting databases,
prescription event monitoring,
electronic health records,
patient registries, and
record linkage between health databases
These data are reviewed to highlight potential
safety concerns in a process known as
data mining.

4.  To market a drug , the manufacturer must
provide evidence of its efficacy and safety to
the U.S Food and Drug Administration(FDA)
 PHASES OF CLINICAL TRIALS
1) Phase 0 : micro dosing
2) Phase I : First in man- Safety
3) Phase II: First in Patient- Dose , dosage forms
4) Phase III: Efficacy , ADRs
5) Phase –IV or Post-marketing Surveillance-
Evaluation of in the real clinical setting.

6. In Premarketing testing , the numbers and type
of patient used to demonstrate a drug`s efficacy
and safety are limited as compared with the
numbers and type of patient who will eventually
be prescribed the drugs after it is marketed.
Although post-marketing surveillance cannot
provide knowledge of the safety or efficacy of the
drug at the time of there introduction into the
market.

7.  Post-marketing surveillance of drug
therefore play an important role to discover an
undesirable effect that might present at risk
It provide additional informationon the benefit and
risk of the drugs.
PMS also allows for long-term monitoring of the
effects of drugs

8. No fixed duration/Patient population
Starts immediately after marketing
Report all ADRs
Help to detect : Rare ADRs
Drug interaction

9. POST-MARKETING SURVEILLANCE
Post marketing surveillance refers to any means
of obtaining information about a product after it
has been approved for public use.
 Section 505(0)(3) authorizes FDA to require certain
post marketing studies and clinical trials for
prescription drugs approved under section 505(b)
and biological product approved under section
351.

10. HISTORY
 In the 1960 at least two serious drugs reactions were
observed in many patient . thalidomide causes limbs
deformities (phocomelia).
The PMA, senator Edward Kennedy (D-Mass.) suggested
that a better system was need for monitoring the use and
effects of prescription drug after they are marketed.
As a result, the joint commission on Prescription Drugs Use
was established in 1976,funded largely by the drug industry,
with the mandate to design a post-marketing surveillance
system to detect , quantify and describe the anticipated and
unanticipated effects of marketed drugs.
The delayed discovery of the adverse effects spurred effects
to improve post-marketing surveillance.

11. Limitations of Premarketing
Clinical Trials
Size of the patient population studied
Narrow population - often not providing sufficient
data on special groups
Narrow indications studied
Short duration

12. SOURCES OF PMS INFORMATION
Expert user groups(focus groups)
customer surveys.
 Customer complaints and warranty claims
Post CE-market clinical trials.
Literature reviews.
Device tracking/implant registries.
User reaction during training programmers.
The media.

13. BENEFITS TO A PMS SYSTEM
Detection of manufacturing problems
improvement of medical device quality
verification of risk analysis
intelligence of long-term performance
chronic complications
 performance trends
performance in different user populations

14. IMPORTANCE OF PMS
 The primary objective of post-marketing
surveillance is to develop information about
drug effects under customary condition of
drug use.
 Rare adverse events may not be detected in
pre- licensure studies because in very large
clinical trials have limitation.
To assess a known serious risk related to the
use of the drug

15. To assess signals of serious risk related to the
use of the drug
To identify an unexpected serious risk when
available data indicates the potential for a
serious risk
Risk of drug- drug/food interaction
Long term effects
Increase in non-medical data sources- e.g.
Pharmacy, supermarket , employer vaccination.

16. Types of Post-marketing Surveillance
1) Spontaneous/voluntary reporting of cases
- National (FDA MedWatch)
- Local or Regional (Joint Commission
Requirement)
- Scientific literature publications
2) Postmarketing studies (voluntary or required)
- Observational studies (including automated
healthcare databases)
- Randomized clinical trials
3) Active surveillance
- Drug-Induced Liver Injury Network (DILIN)
-Sentinel initiative

17. Spontaneous Reports
A communication from an individual (e.g.
health care professional, consumer) to a
company or regulatory authority
Describes a suspected adverse events
Passive and voluntary reports

19. FDA Adverse Event Reporting System
(FAERS)
Computerized database
Spontaneous reports
Contains human drug and therapeutic biologic reports
> 7 million reports since 1969
FAERS Strengths
 Includes all U.S. marketed products
Includes all uses
Includes broad patient populations: elderly, children,
pregnant women, co-morbidities
Simple, relatively inexpensive reporting system
Especially good for events with a rare background rate

20. METHODS OF SURVEILLANCE
four types of studies are generally used to
identify drugs effects:
1. Controlled clinical trials,
2. Spontaneous or voluntary recording
3. Cohort studies
4. Case control studies

21. 1) CONTROLLED CLINICAL TRIALS
 PMS studies conducted after the launch of a
product is part of phase IV development of drug.
Some of these studies may be retrospective case-
control evaluation
These are done to evaluate rare suspected side
effects.
For eg: when there was a suspicion that use of oral
contraceptives may be associated with an increased
incidence of thrombophlebitis (clotting of blood in
the deep veins ) and thromboembolism (blockage of
smaller arteries due to detached blood clots) case-
control studies were carried out.

22. A group of cases of thromboembolism were
compared with age matched controls that were
similar to the cases as possible, but without the
disease.
• To minimize bias through such method as
randomization
and “double-blinding
• Directly monitor patients for the duration of
studies.
• For evaluating a drug‟s efficacy and safety.
• They are often costly.

23. 2)SPONTANEOUS REPORTING
A communication from an individual (e.g: health
care professional, consumer) to a company or
regulatory authority
This describes a suspected adverse events
But the actual incidence of adverse drug reaction
cannot be determined through spontaneous
reporting
The spontaneous reporting system process
1. Data acquisition
2.data assessment
3.data interpretation

24. 1. Data acquisition :
which depends largely on the input of information derived
from reports submitted by the health professionals who have
encountered what they suspect is an ADR
2. Data assessment :
which involves assessment of the individual case reports and
assessment of pooled data obtained from various sources
such as the international database of the WHO The
spontaneous reporting system.
3. Data interpretation
based on the available data and the assessments made, a
signal related to the adverse reaction may be generated

25.  India – ‘Suspected Adverse
Drug Reaction Reporting Form’
UK – ‘Yellow Card’, since 1964
Australia – ‘Blue Card’ , since 1964
US – ‘Med Watch’

26.  yellow card
• Introduced in 1964 (Sir Derrick Dunlop) after
thalidomide tragedy
• Over 600,000 confidential reports have been
received in UK
• Doctors, dentists, pharmacists, coroners, nurses,
midwifes, health visitors
• Non medical prescribers and now patients
• MHRA can detect duplicate reports

28. Information to include on a Yellow Card
4 critical pieces of information that must be included on the
report :-
-Suspected drug
- Suspect reaction
-Patient details
-Reporter details

29. Suspected Drugs
• Name of medicine
• including brand and batch number if known Route
of administration
• Daily dose
• Date medicine started and stopped if applicable
• Reason why the medication was given
• Multiple drugs can be listed if more than one drug is
suspected of causing the reaction

30. Suspect reaction
Describe the reaction Include a diagnosis if
relevant Include when the reaction occurred
whether the reaction was considered to be
serious and complete tick box for reasons why
Document if any treatment was given for the
reaction Eventual outcome tick relevant box

31. Patient Details
• Sex of the patient
• Age at time of reaction
• Weight if known
• Do not need to know name or DOB as this could
identify patient and break patient confidentiality
• Patients initials and local identification number
(hospital or practice number) which will identify
patient to you in the event of future
correspondence

32. Reporter details
Must be completed in all cases
Name and full address : Need to acknowledge
receipt of report and follow up further
information if necessary.
Profession

34. How is the Yellow Card data used to
improve patient safety?
1.Changes to SPC e.g. restriction in use, special
warnings and precautions
2.Publication of
3. Issue of ‘Dear Healthcare professional’ letters
4. Drug Analysis Prints (DAPs)
5. Withdrawal of a medicines if patient safety is
threatened

35. 3. Cohort studies
Studies follow a defined group of patient for a period of
time.
Patient are not randomly assigned , & there is no blinding.
Other names of cohort study are Longitudinal study,
Incidence study and forward looking study
Features of cohort studies
• Cohorts are identified prior to appearance of disease
under investigation
• The study groups are observed over a period of time to
determine the frequency of disease among them
• The study proceeds from cause to effects

36. Indications for cohort study
• There is good evidence of an association between
exposure and disease, from other studies.
• Exposure is rare.
• Attrition of study population can be minimized.
• Sufficient fund is available.

38. Consideration during selection of
Cohort
• The cohort must be free from disease under study.
• Insofar as the knowledge permits, both the groups
should be equally susceptible to disease under study.
• Both the groups must be comparable in respect of
all variable which influence the occurrence of disease
• Diagnostic and eligibility criteria of the disease must
be defined beforehand

39. Types of cohort study
• Prospective study
• Retrospective cohort study
• Ambi-directional cohort study

41. Advantage of Cohort Studies
• Temporality can be established
• Incidence ca be calculated.
• Several possible outcome related to exposure can be
studied simultaneously.
• Provide direct estimate of risk.
• Since comparison groups are formed before disease
develops certain forms of bias can be
minimized like misclassification bias.
• Allows the conclusion of cause effect relationship

42. Disadvantage of Cohort Studies
• Large population is needed
• Not suitable for rare diseases.
• It is time consuming and expensive
• Certain administrative problems like loss of staff, loss of
funding and extensive record keeping are common.
• Problem of attrition of initial cohort is common
• Study itself may alter people’s behavior

43. 4. CASE CONTROL STUDIES
Case control studies identify patient with the adverse
effects to be studied, and compare them with the sample
drawn from the same cohort that gave rise to cases.
Case-Control Studies
A case control study involves two populations – cases and
controls and has three distinct features :
 Both exposure and outcome have occurred before the start
of the study.
 The study proceeds backwards from effect to cause.
 It uses a control or comparison group to support or refute
an inference.

45. ELEMENTS OF A CASE CONTROL
STUDY
1. SELECTION OF CASES
2. SELECTION OF CONTROLS
3. INFORMATION ON EXPOSURE
4. ANALYSIS

46.  Selection of cases
• All people in source population who develop
the disease of interest
-Sample of cases
-Independent of the exposure under study
• Clear definition of outcome studied
• Prevalent vs. incident cases
-Prevalent cases may be related more to
survival with disease than to development of
disease.

47.  Sources of cases
• Hospital/clinic based
-cases Easier to find
-May represent severe cases
• Population based (cancer registry)
- not biased by factors drawing a patient to a
particular hospital

48. Selection of controls
• Represent the distribution of exposure in the
source population of cases -Selected from the
same source population that gives rise to the
cases
• Selected independently of their exposure
status

49. MATCHING
Defined as “ the process by which we select controls in such
a way that they are similar to cases with regard to certain
pertinent selected variable which are known to influence
the outcome of disease and which if not adequately for
comparability could distort or confound the result ”
 TYPES OF MATCHING
• Type 1 Group Matching
• Type 2 Pair matching:

50. 1) Group Matching:
- assigning cases to subcategories based on their
characteristics like age occupation, etc. and then
establishing appropriate controls.
2) Pair matching:
-It is finding a control for particular case as closely
resembling as possible except for disease under
study.

51. ODDS RATIO
OR = 1 -Odds of exposure among cases and
controls are same -Exposure is not associated
with disease
OR > 1 -Odds of exposure among cases are
higher than controls -Exposure is positively
associated with disease
OR < 1 - Odds of exposure among cases are
lower than controls - Exposure is negatively
associated with disease

52. BIAS
• it is a systematic error in design, conduct or analysis of a
study which leads us to an erroneous conclusion.
• 1.Bias in selection of cases - selection bias or diagnostic
bias
• 2.Bias in investigating controls. - recall bias, the controls are
less likely to recall exposure variables than the cases. -The
interview/tests/investigation etc may lack depth in controls
whereas the cases are thoroughly worked up
• 3. CONFOUNDING BIAS (distortion of study effect with
another effect because of variables EXTRANEOUS to the
exposure affecting the prediction of the disease) When the
disease has multiple risk factors which are related to each
other SOLUTION – MATCHING BETWEEN CASES AND
CONTROLS

53. • 4. Problems due to over matching : -
-This is where a potential confounder ( religion
in substance abuse) is matched among cases
and controls.
-The study thus loses the power of proving an
obvious association.
• 5.Bias in analysis - the presence of a
confounder is mostly identified at the time of
analysis. - It is due to non- uniform
distribution of confounders. Solution –
Stratification ( limit the size of study and no
of confounding factors)

54. Advantages
Efficient - saves time and money
Used for rare diseases, smaller sample sizes
Multiple associations with a disease
Can generate hypotheses for future study
Can be used to examine multiple exposures,
such as smoking and asbestos exposure in
mesothelioma risk

55. Disadvantages
Susceptible to bias – recall, reporting
Prone to methodological errors
Observational
Works for certain types of conditions