By David Fiore, MD

Professor of Family Medicine, University of Nevada, Reno

Dr. Fiore reports no financial relationships relevant to this field of study.

SYNOPSIS: Simple, low-cost reminder pill bottles did not lead to more improvement in medication adherence in patients with documented poor adherence.

SOURCE: Choudhry NK, Krumme AA, Ercole PM, et al. Effect of reminder devices on medication adherence: The REMIND Randomized Clinical Trial. JAMA Intern Med 2017;177:624-631.

As Kronish and Moise noted in the editorial accompanying this article,1 in the 1970s David Sackett, MD, and colleagues published groundbreaking work on medication compliance (as it was then called), revealing that only about half the hypertensive patients they studied were taking at least 80% of their medications.2 Unfortunately, more than 40 years later, we still find that medication adherence is a major problem. As reported in the landmark World Health Organization report on medical therapy adherence, rates continue to hover around 50% adherence.3 A recent systematic review and meta-analysis of 771 intervention trials found that there can be a nearly 30% improvement in adherence with intensive, face-to-face intervention.4

Choudhry et al sought to determine if a simple intervention (supplying non-adherent patients with reminder pill bottles) would increase medication adherence. Using a pharmacy benefits database, the researchers selected more than 50,000 patients for study, of which 36,739 were enrolled. To be eligible, patients must have been prescribed between one and three medications for at least one chronic illness, were on commercial insurance, and had filled between 30-80% of their prescriptions (nonadherence was defined as filling < 80% of prescriptions). Patients whose only chronic medication was an antidepressant were followed separately.

There were four arms of the study, three different “reminder bottles” and the control group, which continued to receive their medications in a plain pill bottle. The three study devices were a pill bottle with a toggle strip where each day could be slid over after the pill is taken, a pill bottle cap with a timer that shows the time since the bottle was last opened, and a standard plastic pill box with separate compartments for each day of the week. Patients were mailed the pill bottle devices with an enclosed card explaining how to use them. Patient records were collected for two years (February 2013-March 2015).

Perhaps the most surprising finding of the study, and not anticipated by the researchers, was that more than 15% of the patients in the control group (all “non-adherent” at baseline) became adherent to their medication prescriptions. The adherence rates ranged from 15.1-16.3% in the treatment arms, but all rates were statistically equal. The authors concluded that “no statistically significant difference in adherence was found between those in the control group and those who received a reminder device.”

COMMENTARY

Before we reject the efficacy of simple pill bottle medication reminders, a few issues with this study must be addressed. As the authors admitted, since the devices were mailed to the patients with a card explaining how to use them, there is no way of knowing if the patients actually used the devices (or if they even received them). Furthermore, the large increase in adherence by the control group (more than 15% compared to the 2% adherence the researchers planned for) could obscure any benefit of the intervention. Lastly, using pharmacy data alone may have missed patients who had stopped taking their prescriptions on their doctors’ orders (although this should have been even throughout the study arms).

While it’s disappointing that this study did not find that a simple intervention of mailing non-adherent patients reminder pill bottles, it did show that patients can improve adherence significantly (all groups increased from 0% of patient adherence to approximately 15% adherence). Based on previous studies showing the benefits of face-to-face interventions, I will continue to discuss adherence with my patients and ask them if they think a reminder pill bottle with be helpful.

REFERENCES

  1. Kronish IM, Moise N. In search of a “magic pill” for medication nonadherence. JAMA Intern Med 2017;177:631-632.
  2. Sackett DL, Haynes RB, Gibson ES, et al. Patient compliance with antihypertensive regimens. Patient Couns Health Educ 1978;1:18-21.
  3. World Health Organization. Adherence to Long-Term Therapies: Evidence for Action. Geneva; 2003.
  4. Conn VS, Ruppar TM. Medication adherence outcomes of 771 intervention trials: Systematic review and meta-analysis. Prev Med 2017;99:269-276.