A systematic review of the associations between dose regimens and medication compliance

Background: Previous reviews of the literature on medication compliance hav e confirmed the inverse relationship between number of daily doses and rate of compliance. However, compliance in most of these studies was based on p atient self-report, blood-level monitoring, prescription refills, or pill c ount data, none of which are as accurate as electronic monitoring (EM). Objective: In this paper, we review studies in which compliance was measure d with an EM device to determine the associations between dose frequency an d medication compliance. Methods: Articles included in this review were identified through literatur e searches of MEDLINE(R), PsychInfo((R)), HealthStar. Health & Psychosocial Instruments, and the Cochrane Library using the search terms patient compl iance, patient adherence, electronic monitoring, and MEMS (medication event monitoring systems). The review was limited to studies reporting complianc e measured by EM devices, the most accurate compliance assessment method to date. Because EM was introduced only in 1986. the literature search was re stricted to the years 1986 to 2000. In the identified studies, data were po oled to calculate mean compliance with once-daily, twice-daily, 3-times-dai ly, and 4-times-daily dosing regimens. Because of heterogeneity in definiti ons of compliance, 2 major categories of compliance rates were defined: dos e-taking (taking the prescribed number of pills each day) and dose-timing ( taking pills within the prescribed time frame). Results: A total of 76 studies were identified. Mean dose-taking compliance was 71% +/- 17% (range, 34%-97%) and declined as the number of daily doses increased: 1 dose = 79% +/- 14%, 2 doses = 69% +/- 15%, 3 doses = 65% +/- 16%, 4 doses = 51% +/- 20% (P < 0.001 among dose schedules). Compliance was significantly higher for once-daily versus 3-times-daily (P = 0.008), once -daily versus 4-times-daily (P < 0.001), and twice-daily versus 4-times-dai ly regimens (P = 0.001); however, there were no significant differences in compliance between once-daily and twice-daily regimens or between twice-dai ly and 3-times-daily regimens. In the subset of 14 studies that reported do se-timing results, mean dose-timing compliance was 59% +/- 24%; more freque nt dosing was associated with lower compliance rates. Conclusions: A review of studies that measured compliance using EM confirmed that the prescribed number of doses per day is inversely related to compliance. Simpler, less frequent dosing regimens resulted in better compliance across a variety of therapeutic classes.