Researchers conduct a prospective study that demonstrates an association between alcohol consumption and transitional bladder carcinoma, with a relative risk (RR) of 1.81 and a p-value of 0.03. They then divide the study subjects into 2 groups, smokers and non-smokers, and again examine the association between alcohol consumption and bladder cancer: The discrepancy between the overall results and the stratified results is best explained by which of the following?

Question

Researchers conduct a prospective study that demonstrates an association between alcohol consumption and transitional bladder carcinoma, with a relative risk (RR) of 1.81 and a p-value of 0.03.  They then divide the study subjects into 2 groups, smokers and non-smokers, and again examine the association between alcohol consumption and bladder cancer:  The discrepancy between the overall results and the stratified results is best explained by which of the following?

Quizplus · Accepted Answer

11ec160b_3701_aa1f_9249_adb9f73d4b52_MD0001_00 Confounding occurs when the exposure-disease relationship is muddled by the effect of a confounding variable, an extraneous factor associated with both exposure and disease. An example is shown in the exhibit. In a primary school, it may appear on crude analysis that students with bigger shoe sizes have a higher level of intelligence. However, this association is actually a result of age, not shoe size: Older students tend to have bigger shoe sizes and also to be more intelligent. Age is a confounder because it is associated with both shoe size and intelligence and muddles the association between them. When study subjects are grouped by age (stratification), the association between shoe size and intelligence is no longer significant. Similarly, initial crude analysis suggested that alcohol use was associated with bladder carcinoma (similar to shoe size being associated with intelligence), with a relative risk (RR) of 1.81 and a p-value <0.05. However, smoking is associated with both bladder carcinoma and alcohol use. Therefore, smoking is a potential confounder that may explain the association observed between alcohol use and bladder cancer (similar to age in the school example). Stratified analysis by smoking status shows that both smokers and non-smokers have an RR ~1 with large p-values (>0.05). The RR of 1.81 found on crude analysis disappears and there is no true association between alcohol consumption and bladder cancer. (Choice B) Effect modification results when an external variable positively or negatively impacts the observed effect of a risk factor on disease status. When analysis is performed based on stratification by this external variable, there will be a significant difference in risk between the stratified groups. For instance, aspirin use is associated with Reye syndrome in children but not adults; therefore, age modifies the effect of aspirin on Reye syndrome development. Effect modification can easily be confused with confounding; but stratified analysis can help distinguish between them. With confounding, there is usually no significant difference between the strata (as in this case with the smoker and non-smoker strata). (Choices C and E) Measurement bias and observer bias distort the strength of association by misclassifying exposed/unexposed and/or diseased/nondiseased subjects. The scenario does not describe any issues that could affect the classification process. (Choice D) Meta-analysis refers to compiling results from several studies to increase analysis power. (Choice F) Recall bias results from inaccurate recall of past exposure by people in the study and applies mostly to retrospective (eg, case-control) studies. Educational objective: Confounding occurs when the exposure-disease relationship is muddled by the effect of an extraneous factor associated with both exposure and disease. Confounding bias can result in the false association of an exposure with a disease.

Researchers Conduct a Prospective Study That Demonstrates an Association Between