Three reminder devices had no effect on patients' medication adherence in a recent randomized clinical trial.
The study included participants ages 18 to 64 who were taking one to three long-term oral medications. Patients were enrollees of CVS Caremark, a pharmacy benefit manager whose parent company helped fund and conduct the study, and at baseline, they were not adequately adherent to their medications (medication possession ratio of 30% to 80% in the prior 12 months).
Researchers stratified 53,480 participants (mean age, 45±12 years; 56% female) by medication type (medications for chronic disease or antidepressants) before randomizing them to receive a reminder device in the mail or to a control arm (no device or notification). Patients in the intervention arm received a pill bottle with an affixed strip of toggles that could be moved after each day's dose, a pill bottle cap with a digital timer displaying the time elapsed since the last dose, or a standard pillbox with one compartment for each day of the week.
The primary outcome was optimal adherence to all chronic disease medications over the next 12 months (defined as a medication possession ratio of 80% or more), and secondary outcomes were optimal adherence to cardiovascular medications and to antidepressants. Results were published online on Feb. 27 by JAMA Internal Medicine.
The final analysis included 36,739 patients with chronic diseases and 15,555 patients with depression. Among those with chronic diseases, 15.1% of control patients became optimally adherent during follow-up, compared to 15.5% in the pillbox arm, 15.1% in the digital timer cap arm, and 16.3% in the pill bottle strip arm. There were no significant differences in the adjusted odds of optimal adherence between the intervention arms or controls. In direct comparisons, those who received a pillbox had significantly higher odds of optimal adherence than those who received a pill bottle strip (odds ratio, 1.10; 95% CI, 1.00 to 1.21).
Analyses of secondary outcomes yielded similar results, with none of the devices showing a significant effect on increasing adherence. However, in direct comparisons among those taking antidepressants, the pillbox arm had significantly higher odds of optimal adherence than the digital timer cap arm (odds ratio, 1.14; 95% CI, 1.02 to 1.29).
One reason for the null findings could be the dynamic nature of adherence behaviors, as a higher-than-anticipated 12% to 18% of controls became optimally adherent with no intervention, the study authors noted. Limitations of the study include the small proportion of patients who lost insurance eligibility during the study and potential misclassification of medication dispensing data, they wrote.
Other studies of simple interventions have shown modest improvements in adherence, but more complex, behaviorally oriented approaches are needed to make a large, sustained impact, according to an accompanying editorial. “To make such intensive interventions economical and thus feasible, we first need to improve the detection of nonadherence,” the editorialist wrote.
A cover story in the March ACP Internist offers more details on why reminder devices don't always work, how to uncover nonadherence, and what's new in digital health interventions.