This document discusses pharmacoepidemiology and provides an overview of key concepts: - Pharmacoepidemiology is defined as the study of the use and effects of drugs in large populations. It combines principles from clinical pharmacology and epidemiology. - Several study designs can be used including cohort studies, case-control studies, and case reports. Spontaneous adverse event reporting systems are an important source of pharmacoepidemiology data and can generate hypotheses for further investigation. - Factors that may prompt a pharmacoepidemiological study include regulatory requirements, assessing drug safety in real-world use, and investigating potential issues identified from pre-marketing studies or spontaneous reports.

1. PHARMACOEPIDEMIOLOGY
Presentation by:
Dr. Shrey Bhatia
Junior Resident
Department of Pharmacology
GMC, Patiala
1Dr. Shrey Bhatia

2. What is pharmacoepidemiology ?
2
OVERVIEW
1
Study designs available for pharmacoepidemiological studies2
When should one perform pharmacoepidemiological study ?
Sources of pharmacoepidemiology data.
Special issues in pharmacoepidemiological methodology
3
4
5 Dr. Shrey Bhatia

3. PHARMACOEPIDEMIOLOGY
• Pharmacoepidemiology is the study of the use of and the
effects of drugs in large numbers of people.
• The term pharmacoepidemiology contains two
components: “pharmaco” and “epidemiology.”
3
WHAT IS PHARMACOEPIDEMIOLOGY ?
Dr. Shrey Bhatia

4. PHARMACOEPIDEMIOLOGY versus
CLINICAL PHARMACOLOGY
• Pharmacology : study of the effects of drugs.
• Clinical pharmacology : study of the effects of drugs in
humans
• Central principle of clinical pharmacology : therapy should
be individualized which requires the determination of a
risk/benefit balance
4
WHAT IS PHARMACOEPIDEMIOLOGY ?
Dr. Shrey Bhatia

5. PHARMACOEPIDEMIOLOGY versus
CLINICAL PHARMACOLOGY
5
WHAT IS PHARMACOEPIDEMIOLOGY ?
Dr. Shrey Bhatia
Beneficial and
harmful effects of
the drugs
Clinical status
of the patient
Risk/benefit
balance
Pharmacoepidimiology

6. PHARMACOEPIDEMIOLOGY versus
CLINICAL PHARMACOLOGY
• Pharmacoepidemiology is the implementation of
epidemiological methods, knowledge and logical
justifications in the field of clinical pharmacology via
focusing upon studies on the drug effects on, and drug use
by, large numbers of people.
6
WHAT IS PHARMACOEPIDEMIOLOGY ?
Dr. Shrey Bhatia

7. PHARMACOEPIDEMIOLOGY versus
EPIDEMIOLOGY
• Epidemiology is the study of the distribution and
determinants of diseases in populations.
• Because it investigates drug interactions observed in many
people, pharmacoepidemiology is clearly a sub-branch of
epidemiology
7
WHAT IS PHARMACOEPIDEMIOLOGY ?
Dr. Shrey Bhatia

8. PHARMACOEPIDEMIOLOGY = CLINICAL
PHARMACOLOGY + EPIDEMIOLOGY
8
WHAT IS PHARMACOEPIDEMIOLOGY ?
CLINICAL
PHARMACOLOGY
PHARMACO-
EPIDEMIOLOGY EPIDEMIOLOGY
Dr. Shrey Bhatia
Pharmacoepidemiology takes its focus of knowledge from
clinical pharmacology and the research methods from
epidemiology.

9. HISTORICAL BACKGROUND
THALIDOMIDE DISASTER
• Until the 1950s not enough attention has been
paid to the side effects of drugs.
• 1960’s is the beginning of the discipline of
pharmacoepidemiology
• 1961 : dramatic increase was seen in the
frequency of a previously rare birth defect,
phocomelia; caused by in-utero exposure of
Thalidomide1.
• World Health Organization established a bureau
to collect information from national drug
monitoring organizations
9
WHAT IS PHARMACOEPIDEMIOLOGY ?
PHOCOMELIA:
absence of limbs or
parts of limbs in
patients with in
utero exposure to
thalidomide
1- Ridings JE.The thalidomide disaster, lessons from the past. InTeratogenicityTesting 2013 (pp. 575-586). Humana Press,Totowa, NJ.
Dr. Shrey Bhatia

10. 2- balcik p. pharmacoepidemiology. IOSR Journal Of Pharmacy. 2018;6(2):57-62.
HISTORICAL BACKGROUND
• 1962: the USA, Kefauver–Harris Amendments2 :
strengthened the requirements for proof of drug safety
before a drug could be tested in humans
• 1968: United Kingdom, establishment of the Committee on
Safety of Medicines and Medicines Act of 1968
• The mid-1960s : publication of a series of drug utilization
studies; began a series of investigations of the frequency
and determinants of poor prescribing by physicians
10
WHAT IS PHARMACOEPIDEMIOLOGY ?
Dr. Shrey Bhatia

11. 2- balcik p. pharmacoepidemiology. IOSR Journal Of Pharmacy. 2018;6(2):57-62.
HISTORICAL BACKGROUND
• Other programmes established in various countries2:
Boston Collaborative Drug Surveillance Program
The Joint Commission on Prescription Drug Use
Drug Epidemiology Unit
Drug Safety ResearchTrust ( 1980, UK)
• 1990s and 2000s : inclusion of studies to assess beneficial
drug effects, quality-of-life of patients, meta-analysis, etc.
11
WHAT IS PHARMACOEPIDEMIOLOGY ?
Dr. Shrey Bhatia

12. CONTRIBUTIONS OF PHARMACOEPIDEMIOLOGICAL
STUDIES
• Information which supplements the information available
from premarketing studies
Higher precision : larger sample size
 Effects in Elderly, children, pregnant women
 drug-drug interactions and other illnesses
• New types of information not available from premarketing
studies
Discovery of previously undetected adverse and beneficial effects
Patterns of drug utilization
The effects of drug overdoses
The economic implications of drug use
• General contributions of pharmacoepidemiology
 Reassurances about drug safety 12
WHAT IS PHARMACOEPIDEMIOLOGY ?
Dr. Shrey Bhatia

13. STUDY DESIGNS AVAILABLE
FOR
PHARMACOEPIDEMIOLOGICAL
STUDIES
Dr. Shrey Bhatia 13

14. 14
STUDY DESIGNS AVAILABLE FOR PHARMACOEPIDEMIOLOGICAL
STUDIES
RANDOMIZED CLINICALTRIAL
(Experimental studies)
COHORT STUDIES
CASE-CONTROL STUDIES
SECULARTRENDS
CASE SERIES
CASE
REPORTS
• Analytical
studies
• Control
present
• Descriptive
studies
• Control
absent
Increasingevidencestrength
Dr. Shrey Bhatia

15. 15
STUDY DESIGNS AVAILABLE FOR PHARMACOEPIDEMIOLOGICAL
STUDIES
RANDOMIZED CLINICALTRIAL
(Experimental studies)
COHORT STUDIES
CASE-CONTROL STUDIES
SECULARTRENDS
CASE SERIES
CASE
REPORTS
Exploring the
association
Suggesting
an
association
Analysis of
association
Dr. Shrey Bhatia

16. WHEN SHOULD ONE PERFORM
PHARMACOEPIDEMIOLOGICAL
STUDY?
Dr. Shrey Bhatia 16

17. REASONSTO PERFORM
PHARMACOEPIDEMIOLOGY STUDIES
• Regulatory
 Required by regulatory agencies to have a post
marketing surveillance programme for the drug
17
WHEN SHOULD ONE PERFORM PHARMACOEPIDEMIOLOGICAL STUDY
Dr. Shrey Bhatia

18. REASONSTO PERFORM
PHARMACOEPIDEMIOLOGY STUDIES
• Marketing
To assist market penetration by documenting the safety
of the drug
To protect the drug from accusations about adverse
effects
• Legal
 In anticipation of future product liability litigation
18
WHEN SHOULD ONE PERFORM PHARMACOEPIDEMIOLOGICAL STUDY
Dr. Shrey Bhatia

19. REASONSTO PERFORM
PHARMACOEPIDEMIOLOGY STUDIES
• Clinical
 Hypothesis testing
Problem hypothesized on the basis of drug structure
Problem suspected on the basis of preclinical or premarketing
human data
Problem suspected on the basis of spontaneous reports
19
WHEN SHOULD ONE PERFORM PHARMACOEPIDEMIOLOGICAL STUDY
Dr. Shrey Bhatia

20. REASONSTO PERFORM
PHARMACOEPIDEMIOLOGY STUDIES
Hypothesis generating—need depends on:
• whether it is a new chemical entity
• the safety profile of the class
• the relative safety of the drug within its class
• the formulation
• the disease to be treated
20
WHEN SHOULD ONE PERFORM PHARMACOEPIDEMIOLOGICAL STUDY
Dr. Shrey Bhatia

21. SOURCES OF
PHARMACOEPIDEMIOLOGY
DATA
Dr. Shrey Bhatia 21

22. Spontaneous AE reporting
Global Drug surveillance
Case- control surveillance
Prescription event monitoring
Automated databases
Others
22
SOURCES OF PHARMACOEPIDEMIOLOGY DATA
Dr. Shrey Bhatia

23. 23
SOURCES OF PHARMACOEPIDEMIOLOGY DATA
SPONTANEOUS ADVERSE EFFECTS
REPORTING SYSTEM
Dr. Shrey Bhatia
SPONTANEOUS REPORTING: All unsolicited reports of suspected
adverse events (AEs) from health care professionals or consumers or
pharmaceutical companies, received by the regulatory authorities
( FDA, CDSCO,NCC, AMC etc)*
 Clinical observation that originates outside of a formal study.
 Mainstay of national and international drug safety evaluation in the
post-approval phase3
3- FletcherAP. Spontaneous adverse drug reaction reporting vs event monitoring: a comparison. J R Soc Med. 1991 Jun;84(6):341-4.
*FDA- Food and DrugAdmninistration,CDSCO- Central Drug Standard and Control Organisation, NCC- NationalCoordinationCenter,AMC-
ADR monitoring center

24. 24
SOURCES OF PHARMACOEPIDEMIOLOGY DATA
SPONTANEOUS ADVERSE EFFECTS
REPORTING SYSTEM
Dr. Shrey Bhatia
 Spontaneous reports are confirmed by formal epidemiological
studies (case-control and cohort studies)
CONTRIBUTIONS4
Generate preliminary signals about potential adverse effects and
hypothesis generation with the help of Data Mining
Covers all drugs in whole patient population, including special
subgroup
Inexpensive and simple
4- RAWLINS, MICHAEL D. Spontaneous reporting of adverse drug reactions.QJM.1986.59(230): 531-534.

25. 25
SOURCES OF PHARMACOEPIDEMIOLOGY DATA
SPONTANEOUS ADVERSE EFFECTS
REPORTING SYSTEM
Dr. Shrey Bhatia
Data mining
A technique for extracting meaningful, organized information from
large complex databases ;
Computer is used to identify potential signals in large databases

26. 26
SOURCES OF PHARMACOEPIDEMIOLOGY DATA
SPONTANEOUS ADVERSE EFFECTS
REPORTING SYSTEM
Dr. Shrey Bhatia
Signal:
alert if a drug is associated with:
Previously unrecognized hazard
Known hazard more frequent or more serious than expected
• Series ( minimum 3) of cases of similar suspected ADRs in relation to a
particular drug generates a signal
• Provide preliminary information about postulating a hypothesis and
not for testing it

27. 28
SOURCES OF PHARMACOEPIDEMIOLOGY DATA
SPONTANEOUS ADVERSE EFFECTS
REPORTING SYSTEM
Dr. Shrey Bhatia
Next steps for further analysis of hypothesis generated by
spontaneous reports:
 prove or refute these hypotheses;
 estimate the incidence, relative risk, and excess risk of the ADRs;
 explore the mechanisms involved;
 identify special risk groups.

28. 29
SOURCES OF PHARMACOEPIDEMIOLOGY DATA
SPONTANEOUS ADVERSE EFFECTS
REPORTING SYSTEM
Dr. Shrey Bhatia
Concerns with spontaneous reporting:
Underreporting : as high as 98% 3
Amount of information available is often too limited to permit
thorough case evaluation
Reactions which have a long latency, or rarely having a recognised
iatrogenic basis, may remain unrecognised by this technique
Spontaneous reporting of adverse events for a drug tends to peak at
the end of the second year of marketing and then declines thereafter
(Weber effect).
3- FletcherAP. Spontaneous adverse drug reaction reporting vs event monitoring: a comparison. J R Soc Med. 1991 Jun;84(6):341-4.

29. • Initiated by GOI in July 2010
• Indian Pharmacopoeia Commission ( IPC) in an autonomous
institution of Ministry of Health and FamilyWelfare, GOI, functions as
National Coordination Center for PvPI
• Follows spontaneous reporting system for data collection
30
SOURCES OF PHARMACOEPIDEMIOLOGY DATA
SPONTANEOUS ADVERSE EFFECTS
REPORTING SYSTEM- INDIAN SCENARIO
Dr. Shrey Bhatia
PHARMACOVIGILANCE PROGRAMME OF INDIA ( PvPI)

30. 32
SOURCES OF PHARMACOEPIDEMIOLOGY DATA
SPONTANEOUS ADVERSE EFFECTS
REPORTING SYSTEM- INDIAN SCENARIO
Dr. Shrey Bhatia
Ensure
quality,
integrity,
completeness
Causality
assessment of
reports
Reviewing,
analysing,
forwarding reports
toWHO-UMC,
CDSCO
Regulatory
decisions

31. 35
SOURCES OF PHARMACOEPIDEMIOLOGY DATA
GLOBAL DRUG SURVEILLANCE
Dr. Shrey Bhatia
• International effort to harmonize the terms used to describe the
adverse events and to set criteria and definitions for reactions.
• Efforts to harmonize the way data are stored and communicated
internationally.
• The main agencies involved in this work :
WHO –World Health Organisation
CIOMS- Council for International Organizations of Medical Sciences
ICH- International Conference on Harmonisation

32. 36
SOURCES OF PHARMACOEPIDEMIOLOGY DATA
GLOBAL DRUG SURVEILLANCE
Dr. Shrey Bhatia
Medical Dictionary for Regulatory Activities is a clinically validated
international medical terminology dictionary used by regulatory
authorities; endorsed by ICH
ICH E2B format : is a guideline for the transmission format for
information to be included on an adverse reaction case report.

33. 37
SOURCES OF PHARMACOEPIDEMIOLOGY DATA
GLOBAL DRUG SURVEILLANCE
Dr. Shrey Bhatia
Two International Systems:
European Union ( EU)
pharmacovigilance system
WHO-UMC ( Uppsala
Monitoring Center) ,
Sweden

34. 38
SOURCES OF PHARMACOEPIDEMIOLOGY DATA
Global Drug Surveillance:TheWHO
Programme for International Drug Monitoring
Dr. Shrey Bhatia
• 1970 :WHO-sponsored international drug monitoring project set up
atWHO headquarters in Geneva
• 1978 :Transferred to Sweden with the establishment of the WHO
Collaborating Centre for International Drug Monitoring in Uppsala
(now known as the Uppsala Monitoring Center, UMC)
• Full members: 127 countries, Associate members : 28 countries 5
• 1,52,79,436 ICSRs* in database5
5-WHO UMC annual report 2016-17 . * ICSR- individual case safety report

35. 39
SOURCES OF PHARMACOEPIDEMIOLOGY DATA
Global Drug Surveillance:TheWHO
Programme for International Drug Monitoring
Dr. Shrey Bhatia
5-WHO UMC annual report 2016-17 . * ICSR- individual case safety report
COUNTRY DESTRIBUTION OF ICSRs
received in year 2016-17 5
 Maximum: USA, 45%
 India: 3%
In 2017, the Pharmacovigilance
Programme of India (PvPI)- Indian
Pharmacopoeia Commission (IPC), in
Ghaziabad, India, became a WHO
Collaborating Centre.

36. 40
SOURCES OF PHARMACOEPIDEMIOLOGY DATA
GLOBAL DRUG SURVEILLANCE-
European Union pharmacovigilance system
Dr. Shrey Bhatia
EMA ( European Medical Association ) coordinates pharmacovigilance in
the EU
Member states
Member states
Member states
EUDRANET

37. 41
SOURCES OF PHARMACOEPIDEMIOLOGY DATA
CASE–CONTROL SURVEILLANCE
Dr. Shrey Bhatia
Case–Control Surveillance (CCS) uses case– control methodology to
systematically evaluate and detect effects of medications and other
exposures on the risk of serious illnesses, principally cancers.
 monitoring of non-prescription drugs and dietary supplements as
well as prescription drugs.
 assessment of whether genetic polymorphisms modify the effect of
a medication or supplement on the risk of the illness.
 Excellent statistical power for the detection of associations

38. 42
SOURCES OF PHARMACOEPIDEMIOLOGY DATA
CASE–CONTROL SURVEILLANCE
Dr. Shrey Bhatia
Method:
 Multiple CCS are conducted simultaneously
 Individuals with recently diagnosed cancer or nonmalignant
conditions are interviewed in a set of participating hospitals
 Recently diagnosed non-malignant disorders serve as a pool of
potential controls

39. 43
SOURCES OF PHARMACOEPIDEMIOLOGY DATA
CASE–CONTROL SURVEILLANCE
Dr. Shrey Bhatia
Method:
 From time to time a control diagnosis may itself be of interest as the
outcome
 Cases in one analysis may be controls in another.
 CCS database is used for hypothesis testing and discovery

40. 44
SOURCES OF PHARMACOEPIDEMIOLOGY DATA
CASE–CONTROL SURVEILLANCE
Dr. Shrey Bhatia
Interview data:
1. Drug information:
• histories of medication use for 43 indication or drug categories,
e.g., headache, cholesterol lowering, oral contraception,
menopausal symptoms, herbals/dietary supplements.
.

41. 45
SOURCES OF PHARMACOEPIDEMIOLOGY DATA
CASE–CONTROL SURVEILLANCE
Dr. Shrey Bhatia
Interview data:
2. Factors OtherThan Drugs
• Descriptive characteristics (e.g., age, height, weigh, race)
• habits (cigarette smoking, alcohol and coffee consumption)
• Gynaecologic and reproductive factors
• Medical history and family history
• Buccal cell samples for DNA collection, find out susceptibility by
virtue of inherited genotype

42. 46
SOURCES OF PHARMACOEPIDEMIOLOGY DATA
CASE–CONTROL SURVEILLANCE
Dr. Shrey Bhatia
Strengths:
 Non-prescription, prescription and dietary supplements
 Discovery of unsuspected associations
 Assessment of effects after long intervals or durations of use
 Control of confounding
 Accurate outcome data: hospital records/pathology reports
 High statistical power: large database/sample size
 Biologic component: whether genetic polymorphisms modify drug–
disease associations

43. 47
SOURCES OF PHARMACOEPIDEMIOLOGY DATA
CASE–CONTROL SURVEILLANCE
Dr. Shrey Bhatia
Weakness:
 Selection bias: Population-based CCS is infeasible for logistic and
budgetary reasons
 Recall bias

44. 48
SOURCES OF PHARMACOEPIDEMIOLOGY DATA
PRESCRIPTION EVENT MONITORING
Dr. Shrey Bhatia
Prescription-Event Monitoring (PEM)
cohort of users of a medicine is defined from prescriptions and
followed-up for a defined period (often 6-12months) so as to identify all
adverse events occurring in the early post-treatment period.
 both hypothesis generation and testing.
 Signal detection and evaluation in a manner very similar to
spontaneous reporting systems ,with much higher rates of reporting

45. 49
SOURCES OF PHARMACOEPIDEMIOLOGY DATA
PRESCRIPTION EVENT MONITORING
UK model of National Health Services
Dr. Shrey Bhatia
ABBREVATIONS:
DSRU- Drug Safety
Research Unit
PPD- Prescription
Pricing Division
PPA- Prescription
PricingAuthority
GP- General
Practitioner

46. 50
SOURCES OF PHARMACOEPIDEMIOLOGY DATA
PRESCRIPTION EVENT MONITORING
UK model of National Health Services
Dr. Shrey Bhatia
Reference: www.dsru.org

47. 51
SOURCES OF PHARMACOEPIDEMIOLOGY DATA
PRESCRIPTION EVENT MONITORING
Dr. Shrey Bhatia
Strengths:
 Non-interventional in nature and does not interfere with the
treatment-information collected after prescribing decision
 Patients from everyday clinical practice -real world population
 Exposure data from dispensed prescriptions.
 Concerned with Adverse Events- unsuspected ADRs are reported
 Prompting effect of green form to report- more complete than
spontaneous reports

48. 52
SOURCES OF PHARMACOEPIDEMIOLOGY DATA
PRESCRIPTION EVENT MONITORING
Dr. Shrey Bhatia
Weakness:
 All green forms are not returned- selection bias
 Depends on the accuracy of the doctors clinical notes
 Restricted to general practice, hospitals not included
 Patient compliance of taking medication is not measured

49. 53
SOURCES OF PHARMACOEPIDEMIOLOGY DATA
AUTOMATED DATABASES
Dr. Shrey Bhatia
Past two decades have seen a growing use of computerized databases
containing medical care data, so called “automated databases,” as
potential data sources for pharmacoepidemiology studies:
Claim database
• Insurance claims of pharmacy bills, hospital bills
• claims are often closely audited
• provide some of the best data on drug exposure
Medical record database
• computers to record medical information replacing the paper medical record.
• validity of the diagnosis data is better
• uncertain completeness of the data from other physicians/site of care

50. 54
SOURCES OF PHARMACOEPIDEMIOLOGY DATA
AUTOMATED DATABASES
Dr. Shrey Bhatia
Strengths :
 potential for providing a very large sample size.
 databases are relatively inexpensive to use
 claims databases information is complete, unlike medical records
 no opportunity for recall and interviewer bias

51. 55
SOURCES OF PHARMACOEPIDEMIOLOGY DATA
AUTOMATED DATABASES
Dr. Shrey Bhatia
Weakness :
 Uncertain validity of diagnosis data in claim database, unlike medical
records.
 lack information on some potential confounding variables. For
example, smoking, alcohol, date of menopause, etc in claim data
 do not include information on medications obtained without a
prescription or outside of the particular insurance plan
 instability of the population due to job changes, employers’ changes
of health plans,

52. 56
SOURCES OF PHARMACOEPIDEMIOLOGY DATA
AUTOMATED DATABASES
Dr. Shrey Bhatia
Examples :

53. SOURCES OF PHARMACOEPIDEMIOLOGY DATA
OTHER APPROACHES
Dr. Shrey Bhatia
1. Drug utilization studies
• Provides insight into disease and treatment patterns of physicians
• Demographic data about the patient and the prescriber are also
collected
• Example: National Disease andTherapeutic Index* : Ongoing
medical audit where office-based physicians report four times each
year on all contacts with patients during a 48-hour period.
• useful for descriptive studies only, not for analytic studies.
*https://www.jhsph.edu/research/centers-and-institutes/center-for-drug-safety-and-
Effectiveness/research/data-assets/index.html
57

54. SOURCES OF PHARMACOEPIDEMIOLOGY DATA
OTHER APPROACHES
Dr. Shrey Bhatia
2. Disease incidence data:
• Most countries maintain mortality statistics, derived from the death
certificates which also include information on causes of death.
• useful in performing analyses of secular trends
3. Registry data
• Usually these are just a collection of cases, without controls.
• Useful for performing a case–control study
• Spontaneous reporting system provide cases of ADRs
58

55. SOURCES OF PHARMACOEPIDEMIOLOGY DATA
OTHER APPROACHES
Dr. Shrey Bhatia
4. Ad hoc case–control studies
• Cases recruited from whatever source is appropriate for that disease
• More flexibility in their design, allowing one to use community
controls and to tailor the data collection effort to the question at
hand
5. Ad hoc cohort studies
• sales representatives solicit physicians to enroll the next few
patients for whom they prescribe the drug in question and then give
followup information 59

56. SOURCES OF PHARMACOEPIDEMIOLOGY DATA
OTHER APPROACHES
Dr. Shrey Bhatia 60
• Control group is not needed, only measurement of frequency of
medical event: one cannot determine whether the observed
frequency is larger or smaller than would have been expected.
• Expensive
6. Randomized ControlTrial as post marketing surveillance
• They are artificial and raise logistical problems.
• intended to address specific questions about drug efficacy and few
are for drug safety

57. CHOOSING AMONG THE AVAILABLE ALTERNATIVES
Dr. Shrey Bhatia 61
• By considering the characteristics of the pharmacoepidemiology
resources available, as well as the characteristics of the question to
be addressed, choose those resources that are best suited to
addressing the question at hand.
• One may want to use more than one data collection strategy or
resource, in parallel or in combination

58. CHOOSING AMONG THE AVAILABLE ALTERNATIVES
Dr. Shrey Bhatia 62
• Relative size: spontaneous reporting systems,The Netherlands
Automated Pharmacy Record Linkage System, and Prescription-
Event Monitoring
• Relative speed : Studies that use existing data are most quick> RCT
and cohort
• Relative cost, studies that collect new data are most expensive,
randomized trials and cohort studies

59. CHOOSING AMONG THE AVAILABLE ALTERNATIVES
Dr. Shrey Bhatia 63
• Hypothesis generation: all studies, spontaneous reporting
• Hypothesis-strengthening: those that can quickly access, in
computerized form, both exposure data and outcome data
• Hypothesis-testing studies : randomized clinical trial> medical
records

60. SPECIAL ISSUES IN
PHARMACOEPIDIOLOGY
STUDIES
Dr. Shrey Bhatia 64

61. SPECIAL ISSUES IN PHARMACOEPIDIOLOGY STUDIES
Dr. Shrey Bhatia 65
• Referral bias: physicians had been aware of the study objectives and
this might have influenced their referral of cases and hence increased
the apparent relative risk.
• Protopathic bias: arises when the initiation of a drug (exposure)
occurs in response to a symptom of the (at this point undiagnosed)
disease under study (outcome).
BIAS AND CONFOUNDING

62. SPECIAL ISSUES IN PHARMACOEPIDIOLOGY STUDIES
Dr. Shrey Bhatia 66
• Recall bias: caused by differences in the accuracy or completeness of
the recollections retrieved ("recalled") by study participants
regarding events or experiences from the past.
Confounding: A situation in which the effect or association between an
exposure and outcome is distorted by the presence of another variable
BIAS AND CONFOUNDING

63. SPECIAL ISSUES IN PHARMACOEPIDIOLOGY STUDIES
Dr. Shrey Bhatia 67
Confounding by Indication for Prescription/indication bias
BIAS AND CONFOUNDING

64. SPECIAL ISSUES IN PHARMACOEPIDIOLOGY STUDIES
Dr. Shrey Bhatia 68
why individuals and groups of individuals respond differently to
a specific drug therapy, both in terms of beneficial and adverse
effects ?
MOLECULAR PHARMACOEPIDIMIOLOGY
MOLECULAR PHARMACOEPIDIMIOLOGY
A study of the manner in which molecular biomarkers alter
the clinical effects of medications in populations.

65. SPECIAL ISSUES IN PHARMACOEPIDIOLOGY STUDIES
Dr. Shrey Bhatia 69
Pharmacogenetics : the study of how genetic variability is responsible
for differences in patients’ responses to drug exposure ( candidate
approach)
Pharmacogenomics : studies of genetic variability on drug response +
use of genetic information to guide the choice and dose of drug on an
individual basis ( genome-wide approach)
MOLECULAR PHARMACOLOGY

66. SPECIAL ISSUES IN PHARMACOEPIDIOLOGY STUDIES
Dr. Shrey Bhatia 70
With the improvement of the techniques of molecular biology and
the application of these techniques in pharmacogenetic studies it is
expected that exciting developments will take place towards
determining the genetic foundations of drug side effects
MOLECULAR PHARMACOEPIDIMIOLOGY

67. SPECIAL ISSUES IN PHARMACOEPIDIOLOGY STUDIES
Dr. Shrey Bhatia 71
• Research ethics has focused primarily on protecting human subjects
from the risks of research
• Violation of privacy and confidentiality is the chief risk in
pharmacoepidemiology studies.
• Review by an institutional review board (IRB) and full informed
consent have become the cornerstones of the protection of human
subjects from research risks.
BIOETHICAL ISSUES

68. SPECIAL APPLICATIONS OF
PHARMAEPIDIMIOLOGY
STUDIES
Dr. Shrey Bhatia 72

69. SPECIAL APPLICATIONS OF PHARMAEPIDIMIOLOGY STUDIES
Dr. Shrey Bhatia 73
• Drug utilization , definition as perWHO: “marketing, distribution,
prescription and use of drugs in a society, with special emphasis on
the resulting medical, social, and economic consequences”
• Studies are performed to quantify and identify problems in drug
utilization, monitor changes in utilization patterns, or evaluate the
impact of interventions
STUDIES OF DRUG UTILIZATION

70. SPECIAL APPLICATIONS OF PHARMAEPIDIMIOLOGY STUDIES
Dr. Shrey Bhatia 74
• Drug utilization review (DUR) programs have been defined as
“structured, ongoing initiatives that interpret patterns of drug use in
relation to predetermined criteria, and attempt to prevent or
minimize inappropriate prescribing.”
DRUG UTILIZATION REVIEW

71. SPECIAL APPLICATIONS OF PHARMAEPIDIMIOLOGY STUDIES
Dr. Shrey Bhatia 75
• Interventions to improve physician prescribing need to be tested in
rigorous controlled trials before widespread and expensive
implementation.
Evaluating and Improving Physician Prescribing

72. SPECIAL APPLICATIONS OF PHARMAEPIDIMIOLOGY STUDIES
Dr. Shrey Bhatia 76
• Gaps and limitations in our knowledge of many vaccine safety issues
• New research capacity, such as theVaccine Safety Datalink, provides
powerful tools to address many safety concerns
Pharmacoepidemiologic Studies ofVaccine

73. SPECIAL APPLICATIONS OF PHARMAEPIDIMIOLOGY STUDIES
Dr. Shrey Bhatia 77
• Existing data sources have limited utility for medical device
epidemiology because complete documentation of device use is not
routine.
• lack of a detailed identification system (analogous to the National
Drug Code) for medical devices.
Pharmacoepidemiologic Studies of Devices

74. SPECIAL APPLICATIONS OF PHARMAEPIDIMIOLOGY STUDIES
Dr. Shrey Bhatia 78
• Human teratogenesis can only be identified in the postmarketing
setting.
• Pregnancy registries: “high-risk teratogens” (e.g., thalidomide,
isotretinoin )
• case–control approaches: “moderate-risk teratogens” and to
identify relative safety
• Combining the complementary strengths of cohort and case–control
approaches can provide a comprehensive design to identify human
teratogens
Studies of Drug-Induced Birth Defects

75. SPECIAL APPLICATIONS OF PHARMAEPIDIMIOLOGY STUDIES
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• It is possible now to detect many medication errors using large
claims databases,
• possible to link these data with clinical data, laboratory and
diagnosis data
• increasing use of electronic health records should have a dramatic
effect
Study of Medication Errors

76. SPECIAL APPLICATIONS OF PHARMAEPIDIMIOLOGY STUDIES
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• Routine recording of demographic and clinical information on
hospitalized patients, including all drugs
• comparing the rates of events occurring in these patients and
performing cohort studies, one could detect adverse reactions,
whether or not physicians suspected any associations between drugs
and events.
• Hospitals now have ad hoc adverse drug reaction monitoring and
drug use evaluation programs
Hospital Pharmacoepidemiology

77. CHALLANGES
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78. CHALLANGES
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 limited funding opportunities
 Regulatory restriction
 Privacy concerns surrounding human research
 Limited training opportunities

79. SUMMARY
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80. SUMMARY
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• Pharmacoepidemiology is the study of the use of and the effects of
drugs in large numbers of people
• Reasons to perform pharmacoepidemiology studies: regulatory,
marketing, legal, clinical ( hypothesis generation and testing)
• Case reports and case series- useful to suggest an association
• Secular trends and case-control studies- useful to explore these
associations
• RCT, cohort studies: analysing association

81. SUMMARY
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Sources of PE data
 Spontaneous AE reporting
 Global Drug surveillance
 Case- control surveillance
 Prescription event monitoring
 Automated databases
 Others

82. SUMMARY
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•PE can contribute to information about drug safety and effectiveness
that is not available from pre-marketing studies
“There are no really “safe” biologically active drugs.There are
only “safe” physicians.”
Harold A. Kaminetzsky, 1963.

83. THANKYOUFORYOUR
ATTENTION
Dr. Shrey Bhatia 87