A large case-control study was conducted to assess the relationship between tampon use and toxic shock syndrome (TSS). The odds ratio for tampon use among patients with TSS compared to healthy subjects (controls) was reported as 5.0 (95% confidence interval [4.7-5.2), p <0.01). The authors concluded that the risk of TSS was approximately 5 times higher in tampon users; this was based on the assumption that odds ratio is a good approximation of relative risk in this study. Which of the following best supports this assumption?

A. The confidence interval for the odds ratio is narrow

B. The exposure is associated with the disease

C. The incidence of toxic shock syndrome is low

D. The odds ratio is highly statistically significant

E. The sample size is large

correct answer C…compares the odds of exposure among individuals with the disease (cases) to the odds ring the risk (incidence) of disease among exposed individuals to the risk among unexposed individuals. Cohort studies are potentially costly and time-consuming, but case-control studies are relatively inexpensive, less time-consuming, and popular for exploring exposure-disease associations. However, RR cannot be directly calculated in case-control studies as such studies do not follow patients over time or measure disease incidence. The exposure odds ratio (OR) is a measure of association commonly used in case-control studies. It

compares the odds of exposure among individuals with the disease (cases) to the oddsof exposure among individuals without the disease (controls). If the disease is rare (low disease prevalence), disease incidence (number of new cases) is typically low, and the OR generally approximates the RR. This is called the “rare disease assumption.”

Mathematically: given standard contingency tables, RR = [a I (a+ b)] I [c I (c + d)] and OR = ad I be. When the disease is rare, a and c represent small quantities. Therefore, a is negligible compared to b, and c is negligible compared to d; this results in a reasonable mathematical approximation of RR, where RR becomes approximately ad I be, whicl}

equals OR.In addition to the “rare disease assumption,” OR also approximates RR (regardless of disease incidence) when the cases and controls used in a study are representative of individuals with and without the disease in the overall population (with regard to the exposure of interest).(Choice B) The results of the study (OR= 5.0) suggest that the exposure (tampon use) is associated with the disease (toxic shock syndrome). However, this does not affect the approximation of OR to RR.

(Choices A, 0, and E) The p-value <0.01 indicates that the OR is statistically significant. A large sample size decreases the p-value for the OR and makes the confidence interval narrower. As a result, the recision of the estimate increases.However, this does not affect theapproximation of OR to RR.