Venebio, LLC, Richmond, Virginia 23225, USA.
Clin Ther. 2011 Jan;33(1):62-73. doi: 10.1016/j.clinthera.2011.02.003.
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.
长期自我用药的治疗效果受到平均 50%的不依从率的限制。患者健忘是导致非故意不依从的常见因素。采用简单的日期和日期功能（日历包装）的单位剂量包装旨在通过提示患者维持规定的剂量方案来提高依从性。
根据《系统评价和荟萃分析的首选报告项目》（PRISMA）声明，系统地回顾随机对照试验证据，评估日历泡罩包装（CBP）和日历药丸组织者（CPO）对自我管理的长期药物使用的依从性益处和危害。
数据来源包括 MEDLINE 和 Web of Science 以及 Cochrane 图书馆数据库，从其成立到 2010 年 9 月，并与该领域的研究人员进行了交流。关键搜索词包括泡罩日历包装、泡罩包装、药物包装、药物依从性、药物依从性、药物依从性装置、药物容器、药物组织者、多腔室依从性辅助、持久性、药丸盒组织者、处方续药、随机对照试验和续药依从性。选定的研究具有英文标题；随机对照设计；CBP 或 CPO 包装的药物；需要在社区居住的成年人中每天自行服用固体、口服药物超过 1 个月；并且至少有 1 个依从性的定量结果测量。两位审阅者独立提取研究设计、样本量、干预和对照组以及结果的数据。
共有 10 项试验符合纳入标准，共纳入 1045 名受试者，其中 9 项也检测了临床结局（癫痫发作、血压、精神症状）或卫生保健资源利用。试验之间存在很大的异质性，因此无法进行荟萃分析。在 3 项研究中，日历包装是多因素依从性干预的一部分。10 项试验中有 6 项报告了更高的依从性，但只有 1 项研究与临床显著改善相关：CPO 为基础的多因素干预使癫痫发作频率降低 50%。没有研究报告足够的信息来明确地检查与日历包装相关的潜在危害。
所有试验均存在严重的方法学局限性，例如随机分组或盲法不足，或报告有关纳入受试者和脱落的信息不足，导致偏倚风险中等至高，在 2 项研究中，结果数据不可评估。试验通常时间短，样本量小，且依从性结果测量方法各不相同。
日历包装，尤其是与教育和提醒策略相结合，可能会提高药物依从性。方法学上的限制使得无法确定与 CBP 和 CPO 相关的依从性的效果大小和临床益处或危害。需要高质量、足够大且持续时间长的试验来评估此类干预措施的临床效果。
