Why is greater medication adherence associated with better outcomes

The three explanations evaluated were that subjects with greater placebo adherence were 1) more likely to adhere to other medications, 2) had better healthcare behaviors, and 3) had lower risk. The data included more than 800 risk factors from the Women's Health Initiative (WHI), a nationwide study that included women who participated in randomized controlled trials of estrogen plus progestin (n=16,608) or estrogen alone (n=10,739). The median follow-up was 8 years. Linear regression was used to identify factors that predict adherence, and the Cox model was used to test the association between adherence and outcomes with and without adjusting for other risk factors.Greater adherence to placebo was not associated with colon cancer but was substantially and significantly associated with several diverse outcomes: death, myocardial infarction, stroke, and breast cancer. Adherence to hormone therapy had a significantly weaker association with outcomes than placebo adherence. The WHI risk factors only poorly predicted adherence, R2 < 4%, and did not account for the association between placebo adherence and outcome.The results suggest that adherence to placebo is a marker for important risk factors that were not measured by WHI. Once identified these risk factors may be used to increase the validity of observational studies of medical treatment by reducing unmeasured confounding.