WEEK 4: Confounding - guilty by association?

Question 1

What is confounding?

Answer 1

Confounding occurs when there is presence of a 3rd variable, associated with both exposure and outcome and not necessarily in the causal pathway.

occurs when the observed result between exposure and disease differs from the truth because of the influence of the third variable.

Question 2

Examples:
crude mortality rate (crude effect) of City A differs from the rate of City B—but after adjusting for age, the adjusted rates do not differ.

If age distribution differs between the two cities, then age confounds the association.

Research has shown an association between watching TV and CHDs, are there any factors that could confound the association?

Answer 2

Lack of exercise, unhealthy eating

Question 3

A prospective (cohort) study to determine the relationship between lung-CA incidence and heavy drinking was carried out.

Below is a 2x2 table relating lung CA incidence to initial drinking status.

The figures presented in Table 1 are “crude” since there has not been any adjustment for possible confounders.

What measure of association do we use?
Why?
Conclusions
But wait!!!!!!
Could there be any confounders?

Answer 3

In a Cohort study the measure of association is Relative Risk or Risk ratio(RR).
Relative Risk (RR) Calculation:

RR= Risk of Lung CA in Non-Heavy Drinkers / Risk of Lung CA in Heavy Drinkers
​
RR= 10/50 ^ 30/50 =3

Interpretation:
A Relative Risk of 3 implies that individuals with heavy drinking have a threefold higher risk of developing lung cancer compared to those who are not heavy drinkers.

Why Use Relative Risk (RR):

Directly Measures Association: RR directly measures the strength of association between the exposure and the outcome within the cohort.

Interpretability: RR is easy to interpret. An RR of 1 indicates no association, while values above 1 suggest an increased risk, and values below 1 suggest a decreased risk.

Concerns about Confounding:
While the crude RR provides an initial estimate of the association, it does not account for potential confounding variables.

Confounders are variables that are associated with both the exposure and the outcome but are not on the causal pathway.

In this study, confounders could include factors like age, smoking status, occupational exposures, or other lifestyle factors that may independently influence lung cancer risk.

Question 4

What is stratification?

Answer 4

Stratification is the analysis of disease-exposure in separate subgroups of the data defined by one or more potential confounders.
e.g. smoking

Question 5

f the effect disappears after stratification, what does it mean?

What is the effect of positive and negative confounding on the outcome?

Answer 5

If the effect disappears after stratification, then that evidence that smoking is a confounder.
Positive confounder: aRR<cRR
Negative confounder: aRR>cRR

Positive Confounding: The confounder strengthens the observed association between the exposure and the outcome.

Negative Confounding: The confounder weakens the observed association between the exposure and the outcome.

Question 6

Discuss ways of addressing confounding at design stage.

Answer 6

Design stage:

1. Matching
   Concept: Matching involves pairing or grouping participants with similar characteristics in the study groups to control for potential confounders.
2. Randomization
   Randomization involves the random assignment of participants to different exposure groups, ensuring that potential confounders are equally distributed between groups.
3. Restriction
   Restriction involves limiting the study population to a specific subgroup based on a potential confounder.

Question 7

Outline ways of addressing confounding at Analysis stage.

Answer 7

1. Stratification
   Stratification involves analyzing the data within subgroups defined by the potential confounding variable(s).
2. Adjustment (Multivariable Regression):
   Adjustment involves including the potential confounding variable(s) as covariate(s) in a statistical model to estimate the independent effect of the exposure on the outcome.
3. Standardization:
   Standardization involves creating standardized rates or measures of association to compare groups with different distributions of confounding variables.

This means expected rates among the exposed vrs non-exposed are based on a standardized reference population
E.g Bacteriuria has been associated with Kidney disease. Conflicting results have been reported from several studies concerning the role of OCs in bacteriuria.

Question 8

Direct standardization method

Answer 8

Risk in the OC users:
[365(0.012)+836(0.056)+719(0.063)+500(0.222)]/2420= 0.86

Risk in the non-OC users:
[365(0.032)+836(0.04)+719(0.055)+500(0.027)]/2420=0.41

Therefore, standardized RR=2.1 (0.86/0.41)