This document discusses post-marketing surveillance (PMS), which refers to monitoring drugs after they have been approved for public use. PMS is important because clinical trials have limitations in terms of patient population size, duration, and ability to detect rare or long-term effects. Sources of PMS information include spontaneous reporting, studies using medical databases, and manufacturer monitoring. Common PMS methods include spontaneous reporting of adverse drug reactions, cohort studies, and case control studies. PMS can help identify new safety issues and provide more information on drug risks and benefits in diverse patient populations.
1. PMS (POST MARKETING Surveillance)
Submitted To: Submitted By:
Prof. Dr. Harish Dureja Sandeep
( P’ceutical Department M.Pharma
M.D.U , Rohtak ) (DRA)Ist Sem.
Roll no.:1854
2. INDEX
Introduction
History
Benefits of PMS
Sources of PMS
Types of surveillance
Method of surveillance
Manufacturer PMS system
References
3. PHASES OF CLINICAL TRIALS
Phase 0 : micro dosing
Phase I : First in man- Safety
Phase II: First in Patient- Dose , dosage forms
Phase III: Efficacy , ADRs
Post-marketing Surveillance or
Phase –IV : Evaluation of in the real
clinical setting.
4.
5. Introduction
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. cont…
6. Post-marketing surveillance of drug therefore
play an
important role to discover an undesirable effect
that might present at risk.
It provide additional information on the
benefit and risk of the drugs.
7. 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.
8. POST-MARKETING SURVEILLANCE
No fixed duration/Patient population
Starts immediately after marketing
Report all ADRs
Help to detect
Rare ADRs
Drug interaction
Also new uses for drugs[sometimes called
Phase V]
9. 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
10. Benefits of Post-marketing Monitoring :
The ability to study the following:
•Low frequency reactions (not identified in
clinical trials)
•High risk groups
•Long-term effects
•Drug-drug/food interactions
•Increased severity and / or reporting frequency
of known reactions
11. SOURCES OF PMS INFORMATION:
The following may be considered as sources of
information :
Expert user groups
Customer surveys
Customer complaints and warranty claims
Post CE-market clinical trials.
Literature reviews
The media
12. Types of Post-marketing Surveillance
Spontaneous/voluntary reporting of cases
National (FDA MedWatch)
Local or Regional (Joint Commission Requirement)
Scientific literature publications
Postmarketing studies (voluntary or required)
Observational studies (including automated healthcare
databases)
Randomized clinical trials
Active surveillance
Drug-Induced Liver Injury Network (DILIN)
Sentinel initiative
13. Spontaneous Reports
A communication from an individual (e.g.
health care professional, consumer) to a
company or regulatory authority
Describes a suspected adverse event(s)
Passive and voluntary reports
14. Factors Affecting Reporting
Media attention
Litigation (class action lawsuits)
Nature of the adverse event
Type of drug product and indication
Length of time on market
Extent and quality of manufacturer’s surveillance system
Rx or OTC product status
Reporting regulations
15.
16. FDA Adverse Event Reporting System (FAERS)
Computerized database
Spontaneous reports
Contains human drug and therapeutic biologic
reports
> 7 million reports since 1969
17. 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
cont….
18. Useful for events that occur shortly after
exposure
Detection of events not seen in clinical trials
(“signal generation”)
Identification of trends, possible risk factors,
populations, and other clinically significant
emerging safety concerns
19. Safety Signal
Reported information on a possible causal
relationship between an adverse event and a drug
The relationship being previously unknown or
incompletely documented
Supported by multiple case reports
New unlabeled adverse events
An observed increase in a labeled event OR a greater
severity or specificity
New interactions
Newly identified at-risk population
20. Use of Data Mining
Mathematical tool identifies higher-than-
expected frequency of product-event
combinations
Tool for hypothesis generation
Supplements FAERS data review
Does not replace expert clinical case review
21. Developing a Case Series
Identify a well-documented case in FAERS,
published literature, data mining, or other sources
to identify a safety signal.
Using our knowledge of the clinical course of the
disease, formulate a case definition which may
include both clinical features and laboratory
findings, sometimes even demographic
information if we believe the safety signal is for a
specific population.
Complete a thorough database search for
additional cases.
22. Regulatory Actions
Labeling changes – i.e. Warnings, Precautions,
Adverse Reactions
Pharmacovigilance activities - enhanced
surveillance (e.g., expedited reporting), registry,
epidemiology studies
Risk Evaluation and Mitigation Strategy (REMS)
Communication plan, restricted use
Drug Safety Communication (DSC)
Market withdrawal
23. METHODS OF SURVEILLANCE:
Thus, 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
24. CONTROLLED CLINICAL TRIALS:
To minimize bias through such method as
randomization
Directly monitor patients for the duration of
studies.
For evaluating a drug’s efficacy and safety.
They are often costly.
25. SPONTANEOUS REPORTING:
A communication from an individual (e.g:
health care professional, consumer) to a company
or regulatory authority .
This describes a suspected adverse event(S)
But the actual incidence of adverse drug
reaction can not be determined through
spontaneous reporting.
26. COHORT STUDIES:
Studies follow a defined group of patient for a
period of time.
Patient are not randomly assigned
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.
27. MANUFACTURER PMS SYSTEM:
These are some of the type of
knowledge and feed back which can achieved
from a PMS system.
Detection of some manufacturing problems.
Product quality improvement.
Conformation (or otherwise) of risk analysis.
Knowledge of long term
performance/reliability and /or chronic
complication.
28. Knowledge of performance in different user
population.
Feedback on indication of use.
Feedback on instruction for use.
Feedback on use with other devices.
Feedback on customer satisfaction.
Feedback on continuing market viability.
32. References
http://www.fda.gov/Safety/MedWatch
MedWatch Safety Alerts:
http://www.fda.gov/Safety/MedWatch/ucm287881.htm
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInf
ormation/Surveillance/AdverseDrugEffects/ucm082196.htm#
QuarterlyReports
FOOD AND DRUGS ADMINISTRATION, Supplementary
reports to contracts and grants committee on
Medicaid”, from the division of Drugs
Experience, BUREAU OF DRUGS,1982, 10-32.