Confounding:

An Introduction

Philip la Fleur, RPh MSc(Epidem)

Deputy Director, Center for Life Sciences
plafleur@kazcan.com
Epidemiology Supercourse
Astana, July 2012
 Objectives
Review why randomization is used and how it can
minimize confounding
Understand how to identify a confounder
Understand the fundamental logic underlying
adjusted analyses
 Review: Why Randomize?

Emerg Med J 2003;20:164-168

Tadalafil Therapy for Pulmonary Arterial Hypertension (PAH). Circul 2009;119:2894
 Definition of a Confounder

For a variable to be a confounder it should

meet three conditions:
1. The factor must be associated with the exposure
being investigated
2. Must be independently associated with the
outcome being investigated
3. Not be in the causal pathway between exposure
and outcome.
 Higher versus Lower Positive End-Expiratory Pressures
in Patients with the Acute Respiratory Distress Syndrome
NEJM 2004;351:327-36
Understanding Confounding and Adjusting for
Confounding; Qualitative Demonstration
Treatment Group
(N=100)
80 young Result =
20 old Treatment
Control Group (apparently) Worked!
N=100
20 young
80 old
 Treatment Group
80 young The Truth:
20 old RR of Treatment = 1.0
Control Group Risk of Death in Young = 10%
20 young Risk of Death in Old = 20%
80 old
Overall Analysis (all patients)
Dead Alive Total

Treated 8+4 = 12 88 100

Control 2+16 = 18 82 100

Total 30 170 200

 Calculate Relative Risk
Dead Alive Total

Treated 12 88 100

Control 18 82 100

Total 30 170 200

Risk of Dying in Treated: 12/100 = 0.12

Risk of Dying in Control: 18/100 = 0.18

Relative Risk of Dying in Treated Compared to Control = 0.12/0.18 = 0.67

 How do we solve this problem?

Young Patients Old Patients

Treatment Treatment
Control Control
 All Subjects
Dead Alive Total
Treated 12 18 100
Control 18 82 100
Total 30 170 200

Young Subjects Old Subjects

Dead Alive Total Dead Alive Total

Treated 8 72 80 Treated 4 16 20

Control 2 18 20 Control 16 64 80

Total 10 90 100 Total 20 80 100

Risk in Treatment Group: 8/80 = 0.1 Risk in Treatment Group: 4/20 = 0.2

Risk in Control Group: 10/100 = 0.1 Risk in Control Group: 16/80 = 0.2

Relative Risk = 1.0 Relative Risk = 1.0

Higher versus Lower Positive End-Expiratory Pressures
in Patients with Acute Respiratory Distress Syndrome
NEJM 2004;351:327-36
 Definition of a Confounder
For a variable to be a confounder it should meet three
conditions:
1. The factor must be associated with the exposure being investigated
2. Must be independently associated with the outcome being
investigated
3. Not be in the causal pathway between exposure and outcome.

EXPOSURE OUTCOME
(Truck Driving) (Lung Cancer)

CONFOUNDER
(Smoking)
 Example: Do we have a confounder?

Oral Contraceptive Cervical Cancer

Use

Age at first intercourse

= CONFOUNDER?
 Example: Do we have a confounder?

Used OC Never used OC

Cases 450 300
Controls 200 250

Odds Ratio = 1.9

 Example: Do we have a confounder?

Age at first intercourse was < 20 Age at first intercourse was 20+
years years
Used OC Never Used OC Used OC Never Used OC
Cases 400 200 50 100
Controls 100 50 100 200

Estimated = 1.0 = 1.0

Odds Ratio
 Is it a Confounder? Test #1
1. The factor must be associated with the exposure being
investigated
2. Must be independently associated with the outcome
being investigated
3. Not be in the causal pathway between exposure and
outcome.

Oral Contraceptive Use Cervical Cancer

?
Age at First
Intercourse
 Is it a Confounder? Test #1
Exposure
Used OC Never Used OC
Age at first intercourse <20 years 100 (50%) 50 (20%)
Confounder
Age at first intercourse 20+ years 100 (50%) 200 (80%)
Total 200 (100%) 250 (100%)

20% of those who never used OC had an early age of intercourse

50% of those who used OC had an early age of intercourse
 Is it a Confounder? Test #2
1. The factor must be associated with the exposure being
investigated
2. Must be independently associated with the outcome
being investigated
3. Not be in the causal pathway between exposure and
outcome.

Oral Contraceptive Use Cervical Cancer

?
Age at First
Intercourse
 Is it a Confounder? Test #2
Confounder
Age at first Age at first
intercourse <20 intercourse 20+
years years
Cases 600 150
Controls 150 300

Odds Ratio = 8.0

 Is it a Confounder? Test #3
1. The factor must be associated with the exposure being
investigated
2. Must be independently associated with the outcome
being investigated
3. Not be in the causal pathway between exposure and
outcome.

Oral Contraceptive Use Cervical Cancer

Age at First
Intercourse
 Confounding

Relative Risk Relative Risk Relative Adjusted

in the entire in young Risk in old Relative Risk
population people people
Scenario 1 No confounding 3.0 3.0 3.0 3.0
Scenario 2 Confounding 3.0 2.0 2.0 2.0
Scenario 3 Confounding 1.9 1.0 1.0 1.0
The End
End
 References/Bibliography
1. Last JM. A Dictionary of Epidemiology, 4th ed. Oxford University Press, 2001
2. Guyatt G et al. Users Guides to the Medical Literature, 2nd ed. McGraw Hill,
2008
3. Kennedy CC et al Tips for Teachers of EBM: Adjusting for Prognostic Imbalances
(Confounding variables) in studies of therapy or harm. J Gen Int Med 23(3):337-
43 (and associated lecture by G. Guyatt)
4. Streiner GR, Norman DL, PDQ Epidemiology. 2nd Ed. BC Decker Inc. 1998