LAUSR

regularly taking NSAIDs may differ from the general population in their exposure to other BCC risk factors. For example, if the population under study regularly taking NSAIDS also refrain from spending time outdoors, this group may appear to have lower risk of BCC. This could lead observational studies to report risks of BCC associated with NSAID use lower than studies using an experimental design without this source of bias. In practice, predicting the direction of such biases may be quite difficult. Thus, randomized trials such as this one provide not only a window into the true BCC risks associated with aspirin and folic acid, but hints as to the possible directions (and sources) of bias in observational studies as well. As the name ‘Aspirin/Folate Polyp Prevention Study’ implies, the current study was originally intended to examine the outcome of colon polyps, not skin cancer, and did not have individual information on sun exposure. However, the investigators leveraged the randomized design to examine aspirin use, folate supplementation and BCC without the need for detailed lifetime history of ultraviolet radiation exposure. The Women’s Health Initiative, which includes a set of randomized placebo-controlled trials designed to examine heart disease, breast and colorectal cancer, and osteoporotic fractures, has also recently examined the association between medication use (menopausal hormone therapy), supplementation (vitamin D and calcium) and skin cancer risk. Despite the frequency of BCC in the U.S. population, sample size in these studies remains a limitation, particularly for subgroup analysis. In spite of this, the current study represents an example of successfully repurposing an existing randomized trial to both address a new question and examine the magnitude and direction of possible biases reported in existing, highly powered observational studies.