Coleman Craig I, Limone Brendan, Sobieraj Diana M, Lee Soyon, Roberts Matthew S, Kaur Rajbir, Alam Tawfikul
University of Connecticut, School of Pharmacy, 80 Seymour St., Hartford, CT 06102-5037, USA.
J Manag Care Pharm. 2012 Sep;18(7):527-39. doi: 10.18553/jmcp.2012.18.7.527.
Prior research has shown a decrease in medication adherence as dosing frequency increases; however, meta-analyses have not been able to demonstrate a significant inverse relationship between dosing frequency and adherence when comparing twice-daily versus once-daily dosing.
To determine the effect of scheduled dosing frequency on medication adherence in patients with chronic diseases.
A systematic literature search of Medline and Embase from January 1986 to December 2011 and a hand search of references were performed to identify eligible studies. Randomized and observational studies were included if they utilized a prospective design, assessed adult patients with chronic diseases, evaluated scheduled oral medications taken 1 to 4 times daily, and measured medication adherence for at least 1 month using an electronic monitoring device. Manual searches of reference sections of identified studies and systematic reviews were also performed to find other potentially relevant articles. Standard definitions for medication taking, regimen, and timing adherence were used and evaluated. Studies were pooled using a multivariate linear mixed-model method to conduct meta-regression accounting for both random and fixed effects, weighted by the inverse of the variance of medication adherence.
Fifty-one studies, comprising 65, 76, and 47 dosing frequency arms for the taking, regimen, and timing adherence endpoints were included. Unadjusted adherence estimates were highest when the least stringent definition, taking adherence, was used (range for dosing frequencies: 80.1%-93.0%) and lowest when the most stringent definition, timing adherence, was used (range for dosing frequencies: 18.8%-76.9%). In multivariate meta-regression analyses, the adjusted weighted mean percentage adherence rates for all regimens dosed more frequently than once per day were significantly lower compared with once-daily regimens (for 2-times, 3-times, and 4-times daily regimens, respectively: differences for taking adherence: -6.7%, -13.5%, and -19.2%; regimen adherence: -13.1%, -24.9%, and -23.1%; and timing adherence: -26.7%, -39.0%, and -54.2%).
Patients with chronic diseases appear to be more adherent with once-daily compared with more frequently scheduled medication regimens. The use of more stringent definitions of adherence magnified these findings.
先前的研究表明，随着给药频率的增加，药物依从性会降低；然而，在比较每日两次给药与每日一次给药时，荟萃分析未能证明给药频率与依从性之间存在显著的负相关关系。
确定规定的给药频率对慢性病患者药物依从性的影响。
对1986年1月至2011年12月期间的Medline和Embase进行系统文献检索，并人工检索参考文献以确定符合条件的研究。如果研究采用前瞻性设计、评估成年慢性病患者、评估每日服用1至4次的规定口服药物，并使用电子监测设备测量药物依从性至少1个月，则纳入随机和观察性研究。还对已识别研究的参考文献部分和系统评价进行人工检索，以查找其他潜在相关文章。使用并评估了服药、治疗方案和时间依从性的标准定义。采用多变量线性混合模型方法对研究进行汇总，以进行考虑随机和固定效应的荟萃回归，并以药物依从性方差的倒数为权重。
纳入了51项研究，分别有65个、76个和47个给药频率组用于服药、治疗方案和时间依从性终点。当使用最宽松的依从性定义即服药依从性时，未调整的依从性估计值最高（给药频率范围：80.1%-93.0%），而当使用最严格的定义即时间依从性时，未调整的依从性估计值最低（给药频率范围：18.8%-76.9%）。在多变量荟萃回归分析中，与每日一次给药方案相比，所有每日给药频率超过一次的治疗方案的调整加权平均依从率显著降低（分别针对每日2次、3次和4次给药方案：服药依从性差异为-6.7%、-13.5%和-19.2%；治疗方案依从性差异为-13.1%、-24.9%和-23.1%；时间依从性差异为-26.7%、-39.0%和-54.2%）。
与给药频率更高的治疗方案相比，慢性病患者似乎对每日一次给药的依从性更高。使用更严格的依从性定义放大了这些发现。
