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Epidemiology Kept Simple

Chapter 5:

Introduction to Study Design

Chapter 5

Intro to Epi Study Design

5.1 Introduction to Etiologic Research

5.2 Ethical Conduct of Studies in

Human Subjects

5.3 Selected Elements of Study Design

5.4 Common Types of Epidemiologic

Studies

Main types of epidemiologic studies

Observational Studies

Experimental Studies [Chapter 6]

Aggregate-level unit of observation

Person-level unit of observation

Cross-Sectional [Chapter 5]

Longitudinal

Community trials

Ecological [Chapter 4]

Field trials

Clinical trials

Cohort [Chapter 7]

Case-Control [Chapter 8]

We aim to understand the concepts

behind this study design taxonomy

Before considering epi study

design further, let us consider

epidemiologic hypotheses

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Epi Hypotheses1. Studies must address

clearly defined research

hypotheses (“research

questions”)

2. Hypotheses must based

on sound causal

mechanisms in specific

terms that can be tested

3. Hypotheses are

refinement as new

information becomes

available

Hypotheses are like nets;

only he who casts will catch.

-- Novalis

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Selected elements of an epi

research question1. Source population

2. Exposure variable (E)

3. Disease variable (D)

4. Extraneous “confounding” variables (C1, C2,…, Ck)

5. Dose-response

6. Time-response

7. Sample size

Variables

“Yaz” example

E → D

C1─┘

C2─┘

⁞ ⁞

Ck─┘

Example: Does the progestin

in Yaz (DRSP) cause more

venous thromboembolism

(VTE) than 2nd generation

progestins?

Research question in

general terms: Does

exposure E cause disease D

after considering the

contributions of “potential

confounders” C1, C2, …, Ck?

DRSP → VTE

Age ────┘

Trauma──┘

⁞ ⁞

Surgery──┘

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Ethics: Studying Human

Subjects • The Belmont Report

– Respect for

individuals

– Beneficence

– Justice

• IRB oversight

• Data Safety Monitoring

Board (DSMB)

• Informed consent

• Equipoise

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Equipoise • Equipoise ≡

balanced doubt

• Cannot knowingly expose a participant to harm

• Cannot withhold known benefit to study subjects

• What’s left? (ANS: equipoise)

Is equipoise the over-riding

principles of trial ethics?

Scientific Ethics• Ethics = the set of standardized

rules for conducting yourself: like the tax code people are looking for loopholes and shelters while still staying within the rules

• Scientific ethics is beyond “regular” ethics; scientific ethics is “a bending over backwards to obtain intellectual honesty” – “I cannot give any scientist of any age

any better advice than this: The intensity of the conviction that a hypothesis is true has no bearing on whether it is true or not.” (Peter Medewar)

Peter Medewar

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Advocacy vs. Scientific Ethics

• The term “advocacy” is used in the general sense as applied to public health, commercial, political, and other types of interests planned with the end result in mind.”

• Scientific ethics: A bending over backwards to prove oneself wrong.

“I cannot give any scientist of any age any better advice than this: The intensity of the conviction that a hypothesis is true has no bearing on whether it is true or not.”

Sir Peter Medewar

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Selected Study Design

Elements

• Referent group

• Experimentation

• Unit of observation

• “Longitudinalness”

• Case-control vs.

cohort

The Referent Group

• We can only judge the effects of an

exposure relative to the baseline

determined by a referent or “control”group

• “The question of course is not whether

there is an association in the minds of any

particular individuals. The question is

whether the specific exposure contributed

to the causal mechanism of the disease”

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Experimentation

• Question. Does vitamin C (the exposure) prevent colds (the disease outcome)?

• Experimental Study. Assign vitamin C supplementation to some subjects (E+) and gives others a placebo (E-). Compare cold rates in the groups.

• Observational Study. Classifypeople into those who take vitamin C (E+) and those who don’t (E−). Compare cold rates in the groups.

Did the protocol assign the exposure?

Randomized Experiment

Observational cohort

Randomized Experiment vs.

Observational Cohort

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Unit of Observation

• Question. Does cigarettes smoking (the exposure) cause lung cancer (the disease outcome)?

• Person-level data. Classify individuals as smokers or non-smokers. Assess & compare rates of LungCA in exposed and nonexposed groups.

• Aggregate-level data. Classify level of smoking in various regions. Assess & compare rates of LungCA according to regional smoking rates.

Are data available on individuals?

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Longitudinal v X-sectional

• Question. Does exercise (the exposure) prevent diabetes (the disease outcome)?

• Longitudinal measurement. Identify exercisers (E+) & non-exercisers (E−) track individuals experience over time to assess and compare incidence rates of diabetes.

• Cross-sectional measurement. Assess current exercise habits to assess and compare prevalences of diabetes.

Can you track individual experience over time?

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Case-Control vs. Cohort

• Hypothesis. Does cigarette smoking cause lung cancer?

• Cohort. Identify smokers (E+) and non-smokers (E-) assess and compare lung cancer rates

• Case-control sample. Identify lung cancer cases (D+) and non-cases (D-) assess and compare smoking histories (E+/E-)

Selection of subjects based on exposure

(cohort) or disease (case-control) status?

odds of prior exposures

Illustrative Example 5.6: Toxic Shock and Continuous Tampon Use

• 44 cases and 44 friend controls

• 42 (95%) of the 44 cases used tampons

continuously throughout menstruation

• 34 (77%) of 44 controls did similarly

• cases more likely to use tampons

continuously

• Eventually lead to the discovery that Rely

brand tampons were too absorbent

(c) B. Gerstman 2007 Chapter 9 21

Major types of epidemiologic studies

Observational Studies

Experimental Studies [Chapter 6]

Aggregate-level unit of observation

Person-level unit of observation

Cross-Sectional [Chapter 5]

Longitudinal

Community trials

Ecological [Chapter 4]

Field trials

Clinical trials

Cohort [Chapter 7]

Case-Control [Chapter 8]

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TaxonomyI. Experimental studies (“trials”) – Ch 6

II. Observational studies

A. Individual-level data

1. Longitudinal

(a) Cohort studies - Ch 7

(b) Case-control studies – Ch 8

2. Cross-sectional – Ch 5

B. Aggregate-level data Ecological – Ch 4

Exercise 5.1 Instructions

• Clearly state the research question

• Identify the study exposure

• Identify the study outcome

• Determine the type of study according to

our taxonomy

Exercise 5.1A

Epidemiologists suspect that avian adeno-associated

virus is caused by exposure to poultry. Serum samples

from poultry workers and the general population are

tested to determine the proportion of individuals positive

for avian A–V antibody in each group.

1) experiment or observational

2) individual or aggregate unit of observation

3) longitudinal or X-sectional observation

4) cohort v case-control sample?

Type of study = x-sectional observational study

Exercise 5.1BThe behavioral pattern identified as Type A behavior is characterized by a

hard-driving personality susceptible to anger and time urgency. This type of

behavior is thought to be associated with increased risk for coronary heart

disease. Type A behavior is ascertained in a group of men in a postcoronary

disease rehabilitation program. Men not falling into the Type A category are

classified as Type B. Type A and Type B men are then followed for 5 years to

assess for the recurrence of acute coronary symptoms..

1) observational

2) individual

3) longitudinal

4) cohort

Type of study = observational cohort study

Exerise 5.1G

One hundred incident cases of infectious hepatitis…

1) observational

2) individual-

3) longitudinal

4) case-control sample?

Type of study = case-control!

Exerise 5.1H

Questionnaires are mailed to every tenth person listed…

1) observational

2) individual

3) X-sectional observation

4)

Type of study = x-sectional survey

Exerise 5.1I

An investigator collects information on the size of

manufacturing plants..

1) observational

2) aggregate

Type of study = ecological study!

Exerise 5.2

You have developed a hypothesis that automobile drivers

that talk on their cell phones….

(A) How might you measure the exposure in a cohort

study? Heavy talkers, Non-talkers

(B) How might you identify cases in this [cohort] study

(C)What additional factors…?

(D)What difficulties might be encountered when

measuring

(E) How would we design a case-control study to test…