What is a third variable ?

How to interpret third variable

CHRD SAS
in observational studies
Dr Rukman Mecca Manapurath
Assistant Scientist
CHRD SAS
New Delhi

CHRD SAS
 CHRD SAS
Y
X/exposure
/outcome
?
Z/Third
variable
CHRD SAS
 CHRD SAS
Pancreatic
Coffee drinking cancer

CHRD SAS
Confounder

Coffee CHRD SAS

Pancreatic
drinking cancer

Any variable?
CHRD SAS
Effect modifier

CHRD SAS
Coffee drinking Pancreatic Ca

? CHRD SAS
Mediator

CHRD SAS
Coffee drinking ? Pancreatic Ca

CHRD SAS
Concept – Confounder

CHRD SAS
A third variable that distorts the observed

relation between exposure and the outcome.

Also associated with both exposure & outcome.

CHRD SAS
Concept – Effect modifier

CHRD SAS
Effect of exposure on a disease outcome is

modified by presence of another third variable

CHRD SAS
How will you assess?
Make a crude 2* 2 table
Calculate RR

CHRD SAS Stratify by third variable

Calculate RR for each

strata

Test If RR similar

Possible that 3rd variable is If different, effect

a confounder modification
CHRD SAS
Confounding Criteria
1. Whether in the causalCHRD pathway
SAS of the exposure-
outcome
-using biological and clinical knowledge
2. Associated with both exposure and outcome
3. Unequally distributed among population

CHRD SAS
How to identify?

•First, to find out if the CHRD

assumedSAS
confounding variable is
associated with both outcome variable and exposure
variable
•Second, to compare the associations before and after
adjusting for that confounding factor. CHRD SAS
Coffee n(%) Pancreatic Controls Total
drinking Cancer n(%)
Yes 30 (63) CHRD SAS
18 (37) 48

No 70 (46) 82 (54) 152

Total 100 100 200

Unadjusted RR = 30*82/70*18 = 1.95

Lets consider the third variable – age

CHRD SAS
Step 1- If variable is associated with exposure &
outcome
Age Ca Pancreas Controls

< 40 yrs 50 80
> 40 yrs 50
CHRD SAS20
RR =2.5

100 100 Age is related to having Pancreatic Ca

Age Total Coffee Non Coffee %

Drinkers drinkers exposure
< 40 yrs 130 13 117 10
RR = 5
> 40 yrs 70 35 35 50
100 100
Age is related to being a coffee drinker
CHRD SAS
Step 2- Find adjusted RR & compare it with unadjusted RR

Age Coffee drinking Ca Pancreas Controls Relative

CHRD SAS risk
<40 yrs Yes 5 8 1
No 45 72
Total 50 80
>40 yrs Yes 25 10 1
No 25 10
Total 50 20
Here age is a confounder
CHRD SAS
Limitations- using this stratification, we
cannot check multiple confounders at
one time.
Control at design stage

Matching CHRD SAS

• Matching involves pairing the study groups for potential confounding factors,
such as smoking, age or sex; thus assuring even distribution of potential
confounders

CHRD SAS
Control at analysis stage
• Stratified analyses
CHRD SAS
• Multivariate analyses.
the estimation of the effect of an exposure variable on a given
outcome variable after controlling for the cofounding effect of
other included variable

CHRD SAS
Effect modifier

CHRD SAS
Exposure Outcome

? CHRD SAS
 CHRDonSAS
• Association of exposure an outcome differs
depending on the presence of third variable

• Here exposure and outcome differ in strata of

population
CHRD SAS
Example
Coffee drinkers & Pancreatic Ca - RR of 2.8 (95% CI: 2.5–3.1)
CHRD SAS
After stratifying for gender,
RR of 1.3 (95% CI: 1.1–1.5) among females

Inference?? Gender variable has made some modifications

of the pathway by increasing the risk of pancreatic cancer
among coffee drinkers CHRD SAS
How will you representCHRD
effect modifier
SAS
By strata of population based on third variable

CHRD SAS
Summarize

CHRD SAS
•If an observed association is uniform across stratified groups, it is
called as confounding variable. Whereas, if it is different across
different stratified groups, it is effect modifier.

•If we miss EM sub group pattern will be missed

Confounding Bias occurs CHRD SAS

For data representation
• Do a crude analysis & estimate the measure of association
CHRD SAS
• List potential confounders & modifiers
• Stratify data based on these variables
• Check for Effect modifier Yes
Present adjusted
Data

Yes No
Present by strata Check for confounding CHRD SASNo
Present crude Data
Thank you

CHRD
• Refer to Leon Gordis for SAS
further concepts

• Read more on how to represent effect modifier and

confounder in a observational studies

• Read third variable - mediator

CHRD SAS