The therapeutic benefit of self-administered medications for long-term use is limited
by an average 50% nonadherence rate. Patient forgetfulness is a common factor in unintentional
nonadherence. Unit-of-use packaging that incorporates a simple day-and-date feature
(calendar packaging) is designed to improve adherence by prompting patients to maintain
the prescribed dosing schedule.
To review systematically, in accordance with the Preferred Reporting Items for Systematic
Reviews and Meta-Analyses (PRISMA) statement, randomized controlled trial evidence
of the adherence benefits and harms of calendar blister packaging (CBP) and calendar
pill organizers (CPO) for self-administered, long-term medication use.
Data sources included the MEDLINE and Web of Science and Cochrane Library databases
from their inception to September 2010 and communication with researchers in the field.
Key search terms included blister-calendar pack, blister pack, drug packaging, medication
adherence, medication compliance, medication compliance devices, medication containers,
medication organizers, multicompartment compliance aid, persistence, pill-box organizers,
prescription refill, randomized controlled trials, and refill compliance. Selected
studies had an English-language title; a randomized controlled design; medication
packaged in CBP or CPO; a requirement of solid, oral medication self-administered
daily for longer than 1 month in community-dwelling adults; and at least 1 quantitative
outcome measure of adherence. Two reviewers extracted data independently on study
design, sample size, type of intervention and control, and outcomes.
Ten trials with a total of 1045 subjects met the inclusion criteria, and 9 also examined
clinical outcomes (seizures, blood pressure, psychiatric symptoms) or health care
resource utilization. Substantial heterogeneity among trials precluded meta-analysis.
In 3 studies, calendar packaging was part of a multicomponent adherence intervention.
Six of 10 trials reported higher adherence, but it was associated with clinically
significant improvement in only 1 study: 50% decreased seizure frequency with a CPO-based,
multicomponent intervention. No study reported sufficient information to examine conclusively
potential harms related to calendar packaging.
All trials had significant methodological limitations, such as inadequate randomization
or blinding, or reported insufficient information regarding enrolled subjects and
attrition, which resulted in a moderate-to-high risk of bias and, in 2 studies, unevaluable
outcome data. Trials were generally short and sample sizes small, with heterogeneous
adherence outcome measures.
Calendar packaging, especially in combination with education and reminder strategies,
may improve medication adherence. Methodological limitations preclude definitive conclusions
about the effect size of adherence and clinical benefits or harms associated with
CBP and CPO. High-quality trials of adequate size and duration are needed to assess
the clinical effectiveness of such interventions.
Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.