methods of post marketing surveillance.

1. PRESENTED BY
VIJESHA SONI
PHARM.D. INTERN
NIMS INSTITUTE OF PHARMACY,
NIMS UNIVERSITY, JAIPUR.

2.  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.
 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.

3.  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.

5.  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.
 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.

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

7.  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.  Size of the patient population studied
 Narrow population - often not providing sufficient data on special groups
 Narrow indications studied
 Short duration

9.  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.

10.  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

11.  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.
 Toassess a known serious risk related to the use of the drug
 Toassess 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

12. 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

13.  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

15.  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

16. 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

17.  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.
 A group of cases of thromboembolism were compared with age matched controls that were similar to the cases as possible,
but without the disease.
• Tominimize 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.

18.  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

19. 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

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

21.  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

23.  4 critical pieces of information that must be included on the report :-
 -Suspected drug
 - Suspect reaction
 -Patient details
 -Reporter details

24.  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
 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

25.  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
 Reporter details
 Must be completed in all cases
 Name and full address : Need toacknowledge receipt of report and follow up further information if necessary.
 Profession

27. 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

28.  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.

29. 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.

31.  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

32. 1. Prospective study
2. Retrospective cohort study
3. Ambi-directional cohort study

34.  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

35.  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

36.  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.

38. 1. SELECTION OF CASES
2. SELECTION OF CONTROLS
3. INFORMATION ON EXPOSURE
4. ANALYSIS

39.  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.

40.  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.
 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

41.  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

42. 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.

43. It is a systematic error in design, conduct or analysis of a study which leads us to an erroneous
conclusion.
 Bias in selection of cases - selection bias or diagnostic bias
 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
 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
 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.
 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)

44.  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

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

46. Fundamentals of Clinical Trials, 3rd edition- werence M Friedman, Curt D Furberg,
David L DeMets Pg. No.-42-55
Textbook on Clinical Research: A Guide for Aspiring Professionals-Dr. Guru Prasad
Mohanta Pg. No.- 25-37
Clinical Pharmacy, 2nd edition –H.P.Tipnis, Amrita Bajaj, Pg.No.-313-319