Confounder or Intermediate Variable?

Lead Author(s): Jeff Martin, MD

What Is Not A Confounder?

A variable that is an intermediate step in the causal path under study IF THE VARIABLE IS ON THE PATHWAY UNDER STUDY. IT IS AN INTERMEDIARY VARIABLE.

How do you determine if it is a confounder or an intermediary variable?

Determine Confounder: What Is Your Research Question?

The following example from HIV research shows how you determine if the variable of interest is a confounder or intermediary variable by looking at the research question.

Recently, the human cellular receptor for HIV was determined. We know that CD4 count is a potent predictor of time-to-AIDS.

How should CD4 count be handled in assessing the association So, on the surface, it appears that CD4 count HIV viral load meets the criteria for confounding;


To determine if CD4 count is a confounding variable we ask: We need to stratify to discuss this question:


To stratify you would form homogenous strata of low CD4 count and high CD4 count. Hence, if this is the mechanism you’re proposing and there is no other mechanism, then you do not want to adjust for it. In other words, if knowing the CD4 count is all you need to know about the effect of CCR5,

Adjusting for Confounder to Answer Your Research Question

Taylor published findings on adjusting for the confounder if your research question is:


When the question was asked whether or not a CCR5 defect was associated with progression to AIDS via another mechanism, other than CD4 count, If you had not adjusted for CD4 count first, Hence, you need always need to keep in mind exactly what the research question is and whether or not adjustment is needed to answer it.

Determine Confounder: What Is the Pathway Under Investigation?

After looking at your research question to determine whether you have a confounder or an intermediary variable, the next question is What is the pathway under investigation?

In this example we are looking at the relationship between exercise and CAD, 0402_3HDL.JPG

We know that exercise influences HDL and HDL is associated with coronary artery disease, but is it a confounder or an intermediary?

The answer is that it depends upon the pathway under investigation.

If interest is in a pathway other than through HDL, then HDL is a confounder Confounding factors are extraneous factors

If you really don’t care about the exact pathway or you are only thinking about one pathway by which exercise can influence the development of heart disease, and HDL was right in the middle of this pathway,


Taylor, J. M., Wang, Y., Ahdieh, L., Chmiel, J. S., Detels, R., Giorgi, J. V., et al. (2000). Causal pathways for CCR5 genotype and HIV progression. J Acquir Immune Defic Syndr, 23(2), 160-171.