Epidemiological study designs

Dr Saba Aijaz
MSc. Clinical research (AKUH)
Examples
 Cohort Study
• Exposure to radiation and cancer

• Lead content in drinking water and iron

deficiency anemia
 Cohort Study

Disease
+ -

Exp + a b n1

Exp - c d n0

Mathew J. Reeves, PhD © Dept.

32
of Epidemiology, MSU
Prospective Cohort Study – Multi-sample
Design (select specific exposure groups)

Disease
+ -

Exp + a b n1 Rate= a/ n 1

Exp - c d n0 Rate= c/ n 0

Mathew J. Reeves, PhD © Dept.

33
of Epidemiology, MSU
 Example: Radiation exposure and leukemia

Study: Atomic reactor explosion:

cohort study. Exposed (500) and non exposed(500) followed for ten years
leukemia among radiation exposed compared to non-exposed

Leukemia
+ -

Exp + 50 450 Rate = 50 / 500

Exp - 20 480 Rate = 20 / 500

RR= 2.5
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Example - Smoking and Myocardial Infarction (MI)

Study: Desert island, pop= 2,000 people, smoking prevalence= 50%

Population-based cohort study. Followed for one year.
What is the risk of MI among smokers compared to non-smokers?

MI
+ -

Smk + 30 970 Rate = 30 / 1000

Smk - 10 990 Rate = 10 / 1000

RR= 3

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 Case control Study
• Sudden infant death syndrome and prone
sleeping in infants.

• Viral infection and myocarditis.

• Odds of exposure among cases = a / c
• Odds of exposure among controls = b / d

Disease
case control

Exp + a b

Exp - c d

d1 d0

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 Example CCS - Smoking and Myocardial Infarction
Study: Desert island, population = 2,000 people, prevalence of
smoking = 50% [but this is unknown], identify all MI cases that
occurred
• over last year (N=40), obtain a random sample of N=40
controls (no MI). What is the association between smoking and MI?
MI
+ -

Smk + 30 20

Smk - 10 20

40 40

OR = a . d = 30 . 20 = 3.0 (same as the RR!)

c.b 10 . 20
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 Example CCS – SIDS infants and prone sleeping among
Study: identify all SIDS cases that occurred over last 06 months
(N=100), obtain a random sample of N=100 controls (no SIDS). What
is the association between prone sleeping and SIDS?

SIDS
+ -

Prone+ 80 60

Supine - 20 40

100 100
OR = a . d = 80 . 40 = 4.0
c.b 20 . 60
 Experimental Study Design
• Investigator completely controls exposure
oType, amount, duration, and
oWho receives it (randomization)

• Multiple types of analysis

• Effect measure: Risk Ratio (Relative Risk),

Relative risk reduction (RRR), Absolute risk
reduction(ARR) and Numbers needed to
treat (NNT)
 Types of trials
Trial

Controlled Not controlled

Randomised Not randomised

Blinded Not blinded

 RCT: Basic Design

Treatment

Eligible Conceal, Randomize, Blind

Sample

Control (Placebo)

Population
of interest

Mathew J. Reeves,PhD ©
44
Dept. of Epidemiology, MSU
RANDOMIZATION outcome

Intervention
no outcome

Study
population
outcome
Control

no outcome

baseline
future

time
Study begins here (baseline point)
 Why is a control group important?
100

80
Improvement

60

40

20

Natural History Hawthorne Placebo Treatment

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 RCT’s – Basic Analysis

Disease

Randomize + -

Exp + a b n1 Rt = a/n1

Exp - c d n0 Rc = c/n0

N
RR = Rt/Rc RRR = 1 – RR
ARR = Rc- Rt NNT = 1/ARR
 Example: Effect of ARB on BP control
Assignment BP <140/80 BP > 140/80 Incidence ratios

ARB (200) 140 60 140/200= 0.7

No ARB (200) 110 90 110/200= 0.55

400 250 150

RR: 0.7/0.55 = 1.23

 Loss to FU, poor compliance, contamination
= Slow death of a trial
Non-compliant Loss to FU ?
Trt Outcome

Contamination (cross-overs)

Control Outcome

?
Non-compliant Loss to FU (drop-outs)

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 Randomize

Intervention Control
Group Group

Got Did NOT get Got Did NOT get

Treatment treatment Treatment treatment

Interntion-
YES YES NO NO
to-Treat

Per protocol YES DROP DROP NO

As Treated YES NO YES NO

 Effect of ITT vs. PP vs. AT analyses on an RCT of CABG vs.
medical treatment in 767 men with stable angina.
Allocated (vs. actual) treatment

Medical Medical Surgical Surgical ARR

(medical) (surgical) (surgical) (medical) (95% CI)
Subjects 323 50 368 26

Deaths 27 2 15 6

Mortality 8.4% 4.0% 4.1% 23.1%

ITT analysis 7.8% (29/373) 5.3% (21/394) 2.4% (-1.0, 6.1)

PP analysis 8.4% (27/323) 4.1% (15/368) 4.3% (0.7, 8.2)

AT analysis 9.5% (33/349) 4.1% (17/418) 5.4% (1.9, 9.3)

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 RCT Advantages

• Best evidence study design

• No inclusion bias (using blinding)
• Controlling for possible confounders
• Comparable Groups (using randomization)
 RCT Disadvantages
• Large trials (may affect statistical power)
• Long term follow-up (possible losses)
• Compliance
• Expensive
• Public health perspective ?
• Possible ethical questions
 Choice of Design
Depends on:
– Research Questions
– Research Goals
– Researcher Beliefs and Values
– Researcher Skills
– Time and Funds
Thank you