Lecture 15: Intro to Pharmacoepidemiology and Drug Safety

Question 1

Pharmacoepidemiology

Answer 1

(PEPI) is the study of the use and

effects of medications in populations

Question 2

Epidemiology (EPI

Answer 2

is the study of
frequency and distribution of disease occurrence as well as factors
associated with disease occurrence
in populations

Question 3

CONTRIBUTION TO PHARMACY PRACTICE INCLUDES

Answer 3

ABILITY TO OPTIMIZE DRUG TREATMENT DECISIONS AND IMPROVE DRUG
SAFETY IN POPULATIONS OF INTEREST
Drug therapy decisions
 Make clinical decisions on the best evidence
 Incorporate evidence-based medicine into clinical practice
 Adverse drug reaction surveillance
 Drug utilization evaluations (DUE)

Question 4

Health care records are used

Answer 4

to provide evidence to make drug therapy
decisions and improve drug safety
Medical records databases
Administrative records databases

Question 5

MULTIPLE NEEDS FOR PEPI STUDIES INCLUDE

Answer 5

LONGER EXPOSURE TO MEDICATIONS,
• LIFECYCLES OF DRUG PRODUCTS,
• MORE DIVERSE POPULATIONS EXPOSED TO MEDICATIONS,
• LARGE QUANTITIES OF Data AVAILABLE POST-CLINICAL TRIALS,
• INCREASED (retrospective) STUDY OF SAFETY SIGNALS AND LITIGATION

Question 6

PEPI STUDIES focus

Answer 6

on Rx use, exposure, effects including drug safety
and Rx effectiveness
Measures on “Disease burden” INCLUDE:
INCIDENCE AND PREVALENCE of drug exposure
4. Other numeric measures include:
Relative Risk and Odds Ratios as a measure of association
between Rx exposure and outcomes

Question 7

Why is there a Need for Pharmacoepidemiology?

Answer 7

 More long-term use of medication means increased exposure to benefits but also
“harms” of medications
 Pre- and post-marketing assessment of product safety is a process that continues
throughout the life of a pharmaceutical product
 Shift from individual case reports and clinical trials to large quantities of information
 Increase in retrospective evaluation of safety signals
 Increase in litigation and a need to better understand drug risks

Question 8

Focus of Pharmacoepidemiology Studies include

Answer 8

Drug use and exposure
- Duration of time individuals continue to refill prescriptions

 Drug effects, including drug safety
 Ex: rates of ligament tears suicide among individuals exposed to a drug versus
those not exposed

 Effects of programmatic efforts to improve drug use
 Implementation of a prospective drug utilization review on rate of medication
utilization

Question 9

Incidence

Answer 9

Number of new cases exposed to a drug in population of interest in a specified period of time
 Example: New users of statins in a given year

Question 10

Prevalence

Answer 10

Number of existing cases exposed to a drug in the population in a specified
period of time
 Example: All people on statins in a given year

Question 11

Incidence Rate

Answer 11

is the fraction of disease occurring in a population.

Question 12

Incidence Rate (exposed) Formula

Answer 12

a / (a+b)

Question 13

Incidence Rate (not exposed Formula

Answer 13

c / (c+d)

Question 14

Relative Risk (RR

Answer 14

the probability of an event (Dx or outcome) occurring in

exposed Pts compared to the probability of same event in non-exposed Pts

Question 15

Relative Risk (RR) Formula

Answer 15

Incidence Rate (exposed)
Incidence Rate (unexposed)

= a / (a+b)
c / (c+d)

Question 16

 If RR > 1

Answer 16

“the risk of [x] in exposed is [RR] times greater than risk in non-exposed”

 May or may NOT be causal

Question 17

If RR < 1

Answer 17

“the risk in exposed is [RR] times less than risk in non-exposed”

 May or may not be protective effect

Question 18

If RR = 1 or if 95% CI includes 1.0

Answer 18

no association

Question 19

Odds Ratio (OR)

Answer 19

Measure of Association’

The likelihood of an event occurring among those exposed to a drug relative to
or compared with the likelihood of the same event occurring among those
unexposed to a drug

Question 20

Odds Ratio (OR) Formula

Answer 20

OR = Likelihood of outcome with drug exposure
Likelihood of outcome without drug exposure

the rate of heart attack among people taking a statin relative to the rate of
heart attack among people not taking a statin

Question 21

If OR > 1

Answer 21

“the odds or chances of [x] in one group [OR] times greater than odds or chances
in the other group”

Question 22

If OR < 1

Answer 22

“the odds or chances of [x] in one group [OR] times less than odds or chances in
the other group”

Question 23

f OR = 1 or if 95% CI includes 1.0

Answer 23

no difference in the chances

Question 24

Benefits of Pharmacoepidemiology

Answer 24

 Identify the rate at which a benefit or an adverse drug reaction occurs
 Identify the risk factors associated with the adverse drug reaction
 Informs the development of guidelines and drug use restrictions within institutions

Question 25

the “5 TOOs” of Pre-Marketing Studies or Clinical trials are

Answer 25

1. Too few
2. Too simple
3. Too median-aged
4. Too narrow
5. Too brief

Question 26

Too Few

Answer 26

Insufficient numbers of individuals exposed to a medication to detect rare events

Question 27

Too simple

Answer 27

Exclude individuals with complex, comorbid conditions or concurrent medication use

Question 28

Too median aged

Answer 28

Exclusion of the very young and very old

Question 29

Too narrow

Answer 29

Tested for a specific indication and not other conditions for which it may be used (‘off-label’)

Question 30

Too brief

Answer 30

Do not assess effects after years of chronic therapy

Question 31

Goals of Post-Marketing Surveillance

Answer 31

Examine long-term effects of drugs
 Detect low-frequency (rare) events
 Assess effectiveness in general practice
 Identify modifiers of effectiveness
 Examples include concomitant pharmacotherapy, co-morbid disease(s

Question 32

Major Concepts in Drug Safety Evaluation

Answer 32

Safety Signals
 Adverse Events
 Adverse Reactions (Adverse Drug Reactions - ADRs)

Question 33

REMS

Answer 33

Risk Evaluation Mitigation Strategy

Strategy to manage a known or potential serious risk associated with a
drug or biological product

Range from simple to complex:
 Simple: Communication plans to ensure that the risks are clearly
communicated to prescriber / physician
 Complex: Use restricted to patients enrolled in a monitoring program

Question 34

Passive surveillance

Answer 34

Spontaneous reporting is the cornerstone of signal generation in United States
 MedWatch is program where healthcare professionals and pharmaceutical manufacturers
complete a form detailing the adverse drug reaction and submit it to FDA
 Adverse Event Reporting System (AERS) is the database supporting the FDA postmarketing safety surveillance program
 Advantage: Relatively inexpensive
 Limitation: Do not have total number of people exposed to drug of interest

Question 35

Active surveillance

Answer 35

Use administrative databases to assess drug exposure and safety signals
 Advantage: Large population of exposed individuals
 Limitation: Do not always have key information necessary to assess causality

Question 36

Thalidomide and Birth Defects

Answer 36

Used as a sedative/hypnotic and multiple myeloma; on the market from 1957-1961
 1957 first sold in Germany and by 1960 it was the top-selling sedative
 >10,000 children in 46 countries were born with physical deformities such as phocomelia

Question 37

Adverse Events

Answer 37

An unintended ‘untoward’ medical occurrence that may or may not be
due to the medication
- Should be reported to FDA via spontaneous system, even if it is not
caused by the medication

DIFFERENT THAN Adverse Drug Reaction (ADR)

Question 38

Rawlins and Thompson
(1977) suggested 2
categories

Answer 38

• A: predictable
• B: Unpredictable

Have evolved in that now theres A-> G categories

Question 39

Category A

Answer 39

Dose related (Augmented)

Question 40

Category B

Answer 40

Non-dose related (Bizaare)

Question 41

Category C

Answer 41

Dose related and time related (Chronic)

Question 42

Category D

Answer 42

Time related (Delyaed)

Question 43

Category E

Answer 43

Withdrawel (End of Use)

Question 44

Category F

Answer 44

Unexpected Failure of therapy (Failure)

Question 45

Category G

Answer 45

Genetic/ Genomic

Question 46

STEPS

Answer 46

System for Thalidomide Education and Prescribing Safety

Question 47

Thliadomide

Answer 47

drug that was developed in the 1950s by the West German pharmaceutical company Chemie Grünenthal GmbH
- originally intended as a sedative or tranquiliser, but was soon used for treating a wide range of other conditions, including colds, flu, nausea and morning sickness in pregnant women

Question 48

Summary

Answer 48

Pharmacoepidemiology (PEPI) is the study of use and effects of drugs in populations;
 its contribution to pharmacy practice includes optimizing drug treatment decisions and
improving drug safety by measuring exposure and effects of exposure to drugs
 Incidence & prevalence are measures of drug use / exposure or “illness burden”
 RR & OR measure association between drug exposure and outcome
 Patient health records and/or administrative databases provide data for drug exposure studies
 Drug exposure provides “real life” information about drug effects in the general population that
may or may not be observed in pre-marketing or clinical trials
 Safety signals, adverse events & adverse drug reactions are major concepts in safety studies
 Passive and active surveillance have benefits and limitations; they are used to quantify safety
signals in post-marketing studies
 Risk evaluation and management strategies (REMS) used to manage a serious risk
associated with a drug or biological product; mandated by FDA via FDAAA