Using a sample of patients starting antiepileptic drug therapy, Kesselheim et al designed a nested case-control study to evaluate whether changes in pill color or shape were more likely to precede lengthy gaps in medication refilling. The authors found that the odds of color discordance occurring immediately before an episode of nonpersistence was 27% greater than in controls for whom no interruption in therapy was observed (adjusted odds ratio, 1.27; 95% CI, 1.04-1.55). Among the subset of patients with a known seizure disorder, the odds were even higher (adjusted odds ratio, 1.53; 95% CI, 1.07-2.18). Changes in pill shape were also more common before cases of nonpersistence, but the difference was not statistically significant. The finding that patients who experience changes in pill color have an increased risk of nonpersistence in their use of essential medications supports reconsidering current regulatory policy that permits wide variation in the appearance of bioequivalent drugs.