A retrospective cohort study investigates the association between a newly approved oral Ja… — USMLE Step 3

A retrospective cohort study investigates the association between a newly approved oral Janus kinase (JAK) inhibitor and the incidence of major adverse cardiovascular events (MACE) in adult patients with severe rheumatoid arthritis. The comparison group consists of patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Over a 3-year follow-up period, the crude relative risk of MACE for patients taking the JAK inhibitor compared to those taking csDMARDs is $1.65$ ( $95\%$ CI, $1.25 - 2.18$ ; $p < 0.01$ ).

Concerned about baseline differences between the groups, the investigators perform a stratified analysis based on a history of tobacco smoking. The results of the stratified analysis are shown below:

Smoking Status	Relative Risk of MACE ( $95\%$ CI)
Active or former smokers	$1.05$ ( $0.85 - 1.29$ )
Never smokers	$1.02$ ( $0.80 - 1.30$ )

Based on these findings, which of the following is the most accurate epidemiological conclusion regarding a history of tobacco smoking in this study?

It acts as a confounding variable because the stratum-specific relative risks are similar to each other but differ from the crude estimate.Answer
B
It acts as an effect modifier because the stratum-specific relative risks are similar to each other but differ from the crude estimate.
C
It acts as an effect modifier because the overall significant association disappears upon stratification.
D
It acts as a confounding variable because the unadjusted relative risk is statistically significant prior to stratification.
E
Its influence on the study outcomes invalidates the results because an inferential statistical test should have been used instead of stratification.

Answer

The correct option states that the variable acts as a confounding variable because the stratum-specific relative risks are similar to each other but differ from the crude estimate.

The correct answer accurately identifies smoking status as a confounding variable based on the principles of stratified analysis. A confounder is an extraneous variable that correlates with both the dependent and independent variables. When investigators stratify data by a confounder, the spurious overall association disappears, revealing that the true relative risks within each stratum are similar to each other (here,

1.05

and

1.02

) but notably different from the crude, unadjusted relative risk (

1.65

Step-by-Step Solution

Analyze the initial, unadjusted measure of association.

The crude relative risk of MACE is

1.65

, suggesting a significant increased risk associated with the JAK inhibitor.

Establishes the baseline relationship before accounting for potential third variables.

Evaluate the measures of association after data stratification.

The relative risks in both strata (active/former smokers and never smokers) decrease to

1.05

and

1.02

, respectively, nullifying the initial association.

Determines the true relationship within isolated subgroups, eliminating the third variable's influence.

Compare the crude relative risk to the stratum-specific relative risks.

The stratum-specific risks are similar to each other but drastically different from the crude risk.

This specific statistical pattern is the hallmark epidemiological definition of a confounding variable, distinguishing it from effect modification.

Key Concept

In a stratified analysis, if the stratum-specific measures of association are similar to each other but differ from the crude measure of association, the stratification variable is a confounder. If the stratum-specific measures differ significantly from one another, the variable is an effect modifier.

Question

Answer

Step-by-Step Solution

Key Concept

Common Mistakes

Topics

More questions from this topic