Challenges in Using Observational Studies to Evaluate Adverse Effects of Treatment

In this issue of the Journal, Friis-Møller and colleagues (pages 1723–1735) report on results from a prospective observational study involving more than 23,000 patients infected with HIV. The study, called the Data Collection on Adverse Effects of Anti-HIV Drugs (DAD) trial, identified a possible increased risk of myocardial infarction associated with exposure to protease inhibitors but not to nonnucleoside reverse-transcriptase inhibitors. Because randomized studies are rarely well powered for evaluating adverse effects of treatment, well-designed observational studies are important.1 However, such studies raise complex questions concerning both the potential confounding of risk associations and the mechanisms by which treatment might . . .