Lecture 27: Confounding 1

Question 1

What is the definition of confounding?

Answer 1

A mixing or muddling of effects when the relationship we are interested in is confused by the effect of something else – the confounder

Question 2

What are the three properties of a potential confounder (important)?

Answer 2

1. Independently associated with the outcome
   -A risk (or protective) factor for the outcome regardless of exposure status
2. Independently associated with the exposure
   -Imbalance in distribution across exposure groups
3. Not on the causal pathway
   - Not how the exposure affects the outcome

Question 3

What can confounding do? 4 things

Answer 3

1. Over -estimation of a true association
2. Under-estimation of a true association
3. Change direction of a true association (Simpson’s Paradox)
   - Risk factor becomes protective factor (and vice versa)
4. Give appearance of an association when not one
   - Go from null to something else

Question 4

How can confounding impact a harmful exposure?

Answer 4

Confounding resulted in over-estimating the true harmful effect of the exposure (association appears stronger than it really is, RR is ‘further away from the null’)

Confounding resulted in under estimating the true harmful effect of the exposure (association appears weaker than it really is, RR is ‘closer to the null’)

Question 5

How can confounding impact a beneficial exposure?

Answer 5

Confounding resulted in over-estimating the true protective effect of the exposure
(association appears stronger than it really is, RR is ‘further away from the null’)

Confounding resulted in under-estimating the true protective effect of the exposure (association appears weaker than it really is, RR is ‘closer to the null’)

Question 6

How do we identify potential confounders?

Answer 6

Plan ahead

Collect information on all potential confounders

Use literature to identify known and suspected risk factors for outcome (property 1)

Collect information on factors strongly associated with exposure, regardless if known risk factor (property 2)

Look for imbalance in potential confounder between groups

Question 7

What are the three ways of controlling for confounding in the study design?

Answer 7

Randomisation (only used in RCT’s)
Restriction
Matching

Question 8

What are the three main factors of randomisation in a RCT?

Answer 8

Works best with large sample size

Need equipoise (genuine uncertainty)

Need intention-to-treat analysis to preserve these benefits

Question 9

How does restriction work when controlling for confounding? (strengths and limitations too)

Answer 9

Restrict sample to one stratum of potential confounder eg. age bracket

Strengths:
Easy and can be applied to all study designs

Limitations:
Can reduce generalisability

Reduces number of potential participants

Potential for residual confounding with imprecisely measured (or broadly defined) confounders

Usually only one potential confounder

Question 10

What is matching and when is it used?

Answer 10

Choose people to make the control/comparison group have the same composition as the case/exposed group regarding the potential confounder.

Usually used in case-control studies

Question 11

What is individual matching vs frequency matching?

Answer 11

Individual:
Each case matched with one or more controls having the same confounding variable characteristic(s)

Frequency:
Matching at aggregated level
it ensures similar proportions of key variables across groups, helping control for confounding without requiring individual matches.

Question 12

What are the strengths and limitations of matching?

Answer 12

Positives
Useful for difficult to measure/complex potential confounders

Can improve efficiency of case-control studies with small number

Negatives:
Individual matching can be difficult and limit number of potential participants

Need special matched analysis for individual matching
- Otherwise will under-estimate the measure of association
- Not a form of controlling confounding in the analyses

Question 13

Controlling confounding in the study design (what is important to remember) basically a review?

Answer 13

Design study to minimise confounding by selection and allocation of participants

All attempt to make groups being compared alike regarding potential confounder(s)

Can’t assess association between potential confounder and outcome

Can’t assess whether truly a confounder

Question 14

Complete the following sentence: In order for something to be a potential confounder, it must…’

Answer 14

Be independently associated with the outcome, associated with the exposure and not on the causal pathway between the exposure and the outcome.

Question 15

Limitations of Controlling for Confounding in Study Design: three

Answer 15

1. Inability to Assess Confounder-Outcome Association: Using matching or restriction prevents studying the effect of the confounder (e.g., alcohol) on the outcome, limiting insight into its risk.
2. Cannot Confirm Confounding:
   Controlling for confounding in design (e.g., through restriction) stops us from comparing associations before and after adjustment, so we can’t verify if confounding was present.
3. Limits on Effect Modification and Generalizability: Restriction prevents investigating effect modification (e.g., if alcohol modifies coffee’s effect on cancer) and limits findings to only the restricted group, reducing generalizability.