Lecture 15: Intro to Pharmacoepidemiology and Drug Safety Flashcards

1
Q

Pharmacoepidemiology

A

(PEPI) is the study of the use and

effects of medications in populations

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2
Q

Epidemiology (EPI

A

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

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3
Q

CONTRIBUTION TO PHARMACY PRACTICE INCLUDES

A

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)

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4
Q

Health care records are used

A

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

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5
Q

MULTIPLE NEEDS FOR PEPI STUDIES INCLUDE

A

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

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6
Q

PEPI STUDIES focus

A

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

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7
Q

Why is there a Need for Pharmacoepidemiology?

A

 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

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8
Q

Focus of Pharmacoepidemiology Studies include

A

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

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9
Q

Incidence

A

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

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10
Q

Prevalence

A

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

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11
Q

Incidence Rate

A

is the fraction of disease occurring in a population.

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12
Q

Incidence Rate (exposed) Formula

A

a / (a+b)

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13
Q

Incidence Rate (not exposed Formula

A

c / (c+d)

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14
Q

Relative Risk (RR

A

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

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

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15
Q

Relative Risk (RR) Formula

A
Incidence Rate (exposed)
Incidence Rate (unexposed)

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

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16
Q

 If RR > 1

A

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

 May or may NOT be causal

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17
Q

If RR < 1

A

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

 May or may not be protective effect

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18
Q

If RR = 1 or if 95% CI includes 1.0

A

no association

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19
Q

Odds Ratio (OR)

A

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

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20
Q

Odds Ratio (OR) Formula

A

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

21
Q

If OR > 1

A

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

22
Q

If OR < 1

A

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

23
Q

f OR = 1 or if 95% CI includes 1.0

A

no difference in the chances

24
Q

Benefits of Pharmacoepidemiology

A

 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

25
the "5 TOOs" of Pre-Marketing Studies or Clinical trials are
1. Too few 2. Too simple 3. Too median-aged 4. Too narrow 5. Too brief
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Too Few
Insufficient numbers of individuals exposed to a medication to detect rare events
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Too simple
Exclude individuals with complex, comorbid conditions or concurrent medication use
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Too median aged
Exclusion of the very young and very old
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Too narrow
Tested for a specific indication and not other conditions for which it may be used (‘off-label’)
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Too brief
Do not assess effects after years of chronic therapy
31
Goals of Post-Marketing Surveillance
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
32
Major Concepts in Drug Safety Evaluation
Safety Signals  Adverse Events  Adverse Reactions (Adverse Drug Reactions - ADRs)
33
REMS
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
34
Passive surveillance
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
35
Active surveillance
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
36
Thalidomide and Birth Defects
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
37
Adverse Events
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)
38
Rawlins and Thompson (1977) suggested 2 categories
- A: predictable - B: Unpredictable Have evolved in that now theres A-> G categories
39
Category A
Dose related (Augmented)
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Category B
Non-dose related (Bizaare)
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Category C
Dose related and time related (Chronic)
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Category D
Time related (Delyaed)
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Category E
Withdrawel (End of Use)
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Category F
Unexpected Failure of therapy (Failure)
45
Category G
Genetic/ Genomic
46
STEPS
System for Thalidomide Education and Prescribing Safety
47
Thliadomide
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
48
Summary
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