A cohort study of 4,000 patients examines the role of vitamin D supplements on the incidence of colon cancer. Relative risk (RR) calculations with their corresponding 95% confidence intervals (CI) are reported for subjects taking vitamin D versus controls after a 5-year follow-up period: A separate double-blind randomized clinical trial assigns 3,900 subjects to vitamin D supplementation or placebo. The following results are reported for subjects taking vitamin D versus placebo after a 5-year follow-up period:
Which of the following best describes the results of both studies?

Question

A cohort study of 4,000 patients examines the role of vitamin D supplements on the incidence of colon cancer.  Relative risk (RR) calculations with their corresponding 95% confidence intervals (CI) are reported for subjects taking vitamin D versus controls after a 5-year follow-up period: A separate double-blind randomized clinical trial assigns 3,900 subjects to vitamin D supplementation or placebo.  The following results are reported for subjects taking vitamin D versus placebo after a 5-year follow-up period:
Which of the following best describes the results of both studies?

Quizplus · Accepted Answer

Explanation: In the cohort study, use of vitamin D supplements was associated with statistically significant lower relative risks (RR) of colon cancer and colon cancer mortality (when adjusted for age and gender) as the RRs were both <1 with confidence intervals (CIs) that do no include the null value (1.0 in the case of RRs). However, with the randomized trial, there was no association between vitamin D supplement use and colon cancer or colon cancer mortality as the CIs included the null value. Confoundingoccurs when the exposure-disease relationship is obscured by the effect of an extraneous factor that is associated with both (in this case, exposure is vitamin D, disease is colon cancer). Randomization helps to remove the effects of both known and unknown confounders. However, for the cohort study, the analysis accounted only for the confounding effects of age and gender, but additional confounding factors (residual confounders) may not have been taken into account, leading to residual confounding. Such factors could include intake of specific nutritients (eg, red meat consumption may be associated with colon cancer and may be less likely among patients who are health-conscious and take supplements, including vitamin D), alcohol consumption (eg, there may be an association between alcohol and colon cancer, and patients who consume large amounts of alcohol may be less likely to use vitamin supplements), or factors that have not been identified. (Choice A) The presence or absence of an association between vitamin D supplementation and colon cancer development is not related to biological plausibility (invoked in trying to prove causation). (Choice B) Lead-time bias is the overestimation of survival due to earlier disease diagnosis. These studies are not evaluating survival. (Choice D) For the randomized study, the confidence intervals for the hazard ratios cross 1.0, so the results are not statistically significant. (Choice E) Sample size is typically determined using an estimate of the expected effect of an intervention along with acceptable error margins. In this trial, the large sample size (3,900 subjects) and relatively high precision (narrow confidence intervals) suggest adequate power. A nonsignificant result (confidence intervals that cross the null) does not imply lack of power. Educational objective: Unknown residual confounders may impact the statistical analysis of study results. Randomization removes the effects of known and unknown confounders.

A Cohort Study of 4,000 Patients Examines the Role of Vitamin