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Electronic Medication Packaging Devices and Medication Adherence A Systematic Review

Kyle D. Checchi, MSc1; Krista F. Huybrechts, MS, PhD1; Jerry Avorn, MD1; Aaron S. Kesselheim, MD, JD, MPH1
[+] Author Affiliations
1Program on Regulation, Therapeutics, and Law, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
JAMA. 2014;312(12):1237-1247. doi:10.1001/jama.2014.10059.
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Published online

Importance  Medication nonadherence, which has been estimated to affect 28% to 31% of US patients with hypertension, hyperlipidemia, and diabetes, may be improved by electronic medication packaging (EMP) devices (adherence-monitoring devices incorporated into the packaging of a prescription medication).

Objectives  To investigate whether EMP devices are associated with improved adherence and to identify and describe common features of EMP devices.

Evidence Review  Systematic review of peer-reviewed studies testing the effectiveness of EMP systems in the MEDLINE, EMBASE, PsycINFO, CINAHL, International Pharmaceutical Abstracts, and Sociological Abstracts databases from searches conducted to June 13, 2014, with extraction of associations between the interventions and adherence, as well as other key findings. Each study was assessed for bias using the Cochrane Handbook for Systematic Reviews of Interventions; features of EMP devices and interventions were qualitatively assessed.

Findings  Thirty-seven studies (32 randomized and 5 nonrandomized) including 4326 patients met inclusion criteria (10 patient interface–only “simple” interventions and 29 “complex” interventions integrated into the health care system [2 qualified for both categories]). Overall, the effect estimates for differences in mean adherence ranged from a decrease of 2.9% to an increase of 34.0%, and the those for differences in the proportion of patients defined as adherent ranged from a decrease of 8.0% to an increase of 49.5%. We identified 5 common EMP characteristics: recorded dosing events and stored records of adherence, audiovisual reminders to cue dosing, digital displays, real-time monitoring, and feedback on adherence performance.

Conclusions and Relevance  Many varieties of EMP devices exist. However, data supporting their use are limited, with variability in the quality of studies testing EMP devices. Devices integrated into the care delivery system and designed to record dosing events are most frequently associated with improved adherence, compared with other devices. Higher-quality evidence is needed to determine the effect, if any, of these low-cost interventions on medication nonadherence and to identify their most useful components.

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Figure 1.
Examples of Electronic Medication Packaging

Left, Medication Event Monitoring System 6 SmartCap (Aardex), which stores patients’ adherence record and, in this model, uses an LCD screen with a central number corresponding to vial openings since midnight and (not shown) indicators around the central number corresponding to hours since the last opening. Right and Inset, Prescript TimeCap (Wheaton Medical Technologies), which stores patients’ adherence records, uses an LCD screen with the time and day when the container was last opened and cues dosing with an audible beep and flashing LCD screen.

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Figure 2.
Difference in Level of Adherence at Individual Study Level, Grouped by Type of Intervention

Studies are ordered by increasing effect size. Studies for which insufficient information was available to estimate 95% CIs are displayed using orange circles. Type of device: 1 = adherence recorder only; 2 = adherence recorder and audiovisual alarm; 3 = adherence recorder and liquid crystal display; 4 = adherence recorder, audiovisual alarm, liquid crystal display; 5 = adherence recorder and real time monitoring. Some studies from Tables 1 and 2 are not included in this figure, either because of the type of statistic reported or because missing descriptive statistics prevented inclusion. Two studies assess both patient interface–only and integrated interventions and are therefore included in both categories.

aActual level of adherence by group not reported.

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