Lecture 15: Intro to Pharmacoepidemiology and Drug Safety Flashcards
Pharmacoepidemiology
(PEPI) is the study of the use and
effects of medications in populations
Epidemiology (EPI
is the study of
frequency and distribution of disease occurrence as well as factors
associated with disease occurrence
in populations
CONTRIBUTION TO PHARMACY PRACTICE INCLUDES
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)
Health care records are used
to provide evidence to make drug therapy
decisions and improve drug safety
Medical records databases
Administrative records databases
MULTIPLE NEEDS FOR PEPI STUDIES INCLUDE
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
PEPI STUDIES focus
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
Why is there a Need for Pharmacoepidemiology?
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
Focus of Pharmacoepidemiology Studies include
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
Incidence
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
Prevalence
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
Incidence Rate
is the fraction of disease occurring in a population.
Incidence Rate (exposed) Formula
a / (a+b)
Incidence Rate (not exposed Formula
c / (c+d)
Relative Risk (RR
the probability of an event (Dx or outcome) occurring in
exposed Pts compared to the probability of same event in non-exposed Pts
Relative Risk (RR) Formula
Incidence Rate (exposed) Incidence Rate (unexposed)
= a / (a+b)
c / (c+d)
If RR > 1
“the risk of [x] in exposed is [RR] times greater than risk in non-exposed”
May or may NOT be causal
If RR < 1
“the risk in exposed is [RR] times less than risk in non-exposed”
May or may not be protective effect
If RR = 1 or if 95% CI includes 1.0
no association
Odds Ratio (OR)
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
Odds Ratio (OR) Formula
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
If OR > 1
“the odds or chances of [x] in one group [OR] times greater than odds or chances
in the other group”
If OR < 1
“the odds or chances of [x] in one group [OR] times less than odds or chances in
the other group”
f OR = 1 or if 95% CI includes 1.0
no difference in the chances
Benefits of Pharmacoepidemiology
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
the “5 TOOs” of Pre-Marketing Studies or Clinical trials are
- Too few
- Too simple
- Too median-aged
- Too narrow
- Too brief
Too Few
Insufficient numbers of individuals exposed to a medication to detect rare events
Too simple
Exclude individuals with complex, comorbid conditions or concurrent medication use
Too median aged
Exclusion of the very young and very old
Too narrow
Tested for a specific indication and not other conditions for which it may be used (‘off-label’)
Too brief
Do not assess effects after years of chronic therapy
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
Major Concepts in Drug Safety Evaluation
Safety Signals
Adverse Events
Adverse Reactions (Adverse Drug Reactions - ADRs)
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
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
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
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
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)
Rawlins and Thompson
(1977) suggested 2
categories
- A: predictable
- B: Unpredictable
Have evolved in that now theres A-> G categories
Category A
Dose related (Augmented)
Category B
Non-dose related (Bizaare)
Category C
Dose related and time related (Chronic)
Category D
Time related (Delyaed)
Category E
Withdrawel (End of Use)
Category F
Unexpected Failure of therapy (Failure)
Category G
Genetic/ Genomic
STEPS
System for Thalidomide Education and Prescribing Safety
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
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
