What is Pharmacoepidemiology?

Question 1

Definition of pharmacoepidemiology

Answer 1

The study of the use of and the effect of drugs in large numbers of people

Pharmacology - FOCUS of inquiry
Epidemiology - METHODS of inquiry

Question 2

Definition of pharmacology

Answer 2

The study of the effects of drugs

Question 3

Definition of clinical pharmacology

Answer 3

The study of the effects of drugs in humans

Question 4

Central principle of clinical pharmacology

Answer 4

Therapy should be individualized, or tailored, to the needs of the specific patient at hand

Question 5

Individualization of therapy

Answer 5

Requires the determination of a risk/benefit ratio specific to the patient at hand

Question 6

Definition of epidemiology

Answer 6

The study of the distribution and determinants of diseases in populations

Pharmacoepidemiology falls within epidemiology

Question 7

Subdivisions of epidemiology

Answer 7

A study of infectious diseases in populations

The study of chronic diseases

Question 8

Major application of pharmacoepidemiology principles

Answer 8

After drug marketing

Question 9

Pure Food and Drug Act (1906)

Answer 9

In response to excessive adulteration and misbranding of the food and drug at the time

No requirement for proof of efficacy or safety of marketed drug

Federal government was allowed to remove drug that was adulterated or misbranded

Question 10

Food, Drug, and Cosmetic Act (1938)

Answer 10

Preclinical toxicity testing was required and manufacturers were required to gather clinical data about drug

No proof of efficacy was required

Question 11

Phase I testing

Answer 11

Determine safety and dosage

Question 12

Phase II testing

Answer 12

Evaluate efficacy, look for side effects

Question 13

Phase III testing

Answer 13

Confirm efficacy, monitor adverse reactions for long term use

Question 14

Phase IV testing

Answer 14

Additional post-market testing

Where pharmacoepidemiology is emphasized

Question 15

Problems with clinical trials

Answer 15

Expensive; small; often drugs are compared against placebo; exclude elderly, children, pregnant women, patients with important comorbidities; may be unethical; not timely

HOWEVER, clinical trials provide gold standard evidence of drug effects

Question 16

FDA Amendment Act of 2007

Answer 16

FDA has the right to require post-marketing studies to be completed

Question 17

Study design: Most causal to least causal

Answer 17

RCT
Cohort
Case-control
Analyses of secular trends
Case series
Case reports

Question 18

Case Reports

Answer 18

A report of an event in a single patient
Useful for generating hypotheses
Simple and inexpensive

Question 19

Case Series

Answer 19

Collections of patients all of whom have either a single exposure or single outcome
NO control group = NO hypothesis testing
Useful to quantify an ADE and ensure particular ADE(s) are not happening in population larger than that studied prior to drug marketing

Question 20

Analyses of Secular Trends (ecological studies)

Answer 20

Examine trends in an exposure that is a presumed cause and trends in a disease that is a presumed effect and test whether the trends coincide
Trends examined over either over time or across boundaries
LACK INDIVIDUAL DATA: Ecological fallacy, no control for confounding variables

Question 21

Case-Control Study

Answer 21

Compare cases (with outcome) to controls (without outcome) to look for differences in antecedent exposure(s)
Useful to study multiple exposures and uncommon diseases
Potential for bias in control selection and exposure determination
Measure of association = OR

Question 22

Cohort Study

Answer 22

A study that identifies a cohort of subjects and follows them over time to determine outcome
Loss to follow-up greater concern

Question 23

Randomized Control Trial

Answer 23

Experimental trials: A study in which the investigator controls the exposure received by each participant
RCT: a study where participants are randomly assigned between exposure and control groups
ONLY DESIGN THAT CONTROLS FOR UNKNOWN CONFOUNDERS

Question 24

Pragmatic Clinical Trials

Answer 24

A study in which the investigator tests the effectiveness of an intervention under “real-world” conditions
Not generalizable
Evidence paradox

Question 25

Evidence Paradox

Answer 25

In order to inform clinicians on how to treat patients, we need real-life patients
People with comorbidities
People who forget to take their medication

Question 26

Relative Risk

Answer 26

Measure of association
Based on incident data
Cohort, RCTs
Ratio of risk
a/(a+b) / c/(c+d)

Question 27

Odds Ratio

Answer 27

Measure of association
Based on prevalent data
Case-control, cross sectional
Ratio of odds
a/c / b/d = ad/bc

Question 28

P-value of significance

Answer 28

< 0.05

Question 29

Significant CI

Answer 29

Not including the null

Question 30

Study results

Answer 30

1. No association: Exposure and effect are independent
2. Artificial association (spurious): Either chance (unsystemic variation) or bias (systemic variation)
3. Indirect association (confounded)
4. Causal association (direct or true)

Question 31

Types of error

Answer 31

1. Random: Tested for and fixed statistically
2. Bias: Avoided with good study design
3. Confounding: Adjusted for when recognized

Question 32

Biases

Answer 32

1. Information bias: Interview bias (probing more thoroughly some subjects more than others) or recall bias (more than just a faulty memory)
2. Selection bias: When controls don’t represent the population that produced the cases or differential loss to follow-up

Question 33

Confounder

Answer 33

A variable related to both the exposure and the outcome
NOT be on the path from exposure to outcome
Confounding occurs when such a variable is distributed unequally between groups