Biochemical markers of compliance in the Physicians' Health Study.

The Physicians' Health Study is a randomized, double-blind, placebo-controlled trial using a 2 x 2 factorial design to test the effects of low-dose aspirin on risk of cardiovascular disease and beta-carotene supplementation on the incidence of cancer. To evaluate self-reported compliance with assigned treatment, we measured serum thromboxane B2, which is decreased after aspirin use, and plasma beta-carotene in samples of study participants drawn from three geographic locations in three different time periods. Thromboxane B2 levels were markedly lower in those assigned to aspirin (median = 63.5 pg/mL) than in those given aspirin placebo (median = 3,600 pg/mL, P less than .0001). Similarly, those assigned to beta-carotene had significantly higher levels (median = 1,176 ng/mL) than those given placebo (median = 306 ng/mL, P less than .0001). In addition, there was a highly significant positive correlation between levels of these biochemical markers and the self-reports of compliance (r = 0.65 for thromboxane B2 and r = 0.69 for beta-carotene, P less than .0001). These findings support the validity of the self-reported compliance in the Physicians' Health Study.