title: A systematic review of the associations between dose regimens and medication compliance.
abstract: BACKGROUND
  Previous reviews of the literature on medication compliance have confirmed the inverse relationship between number of daily doses and rate of compliance. However, compliance in most of these studies was based on patient self-report, blood-level monitoring, prescription refills, or pill count data, none of which are as accurate as electronic monitoring (EM).
  
  
  OBJECTIVE
  In this paper, we review studies in which compliance was measured with an EM device to determine the associations between dose frequency and medication compliance.
  
  
  METHODS
  Articles included in this review were identified through literature searches of MEDLINE, PsychInfo, HealthStar, Health & Psychosocial Instruments, and the Cochrane Library using the search terms patient compliance, patient adherence, electronic monitoring, and MEMS (medication event monitoring systems). The review was limited to studies reporting compliance measured by EM devices, the most accurate compliance assessment method to date. Because EM was introduced only in 1986, the literature search was restricted to the years 1986 to 2000. In the identified studies, data were pooled to calculate mean compliance with once-daily, twice-daily, 3-times-daily, and 4-times-daily dosing regimens. Because of heterogeneity in definitions of compliance, 2 major categories of compliance rates were defined: dose-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-daily regimens (P = 0.001); however, there were no significant differences in compliance between once-daily and twice-daily regimens or between twice-daily and 3-times-daily regimens. In the subset of 14 studies that reported dose-timing results, mean dose-timing compliance was 59% +/- 24%; more frequent 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.
authors.affiliation: Global Health Outcomes Research, Eli Lilly and Company, Indianapolis, Indiana 46285, USA. ami.claxton@lilly.com
authors.forename: A J
authors.initials: AJ
authors.lastname: Claxton
authors.forename: J
authors.initials: J
authors.lastname: Cramer
authors.forename: C
authors.initials: C
authors.lastname: Pierce
mesh_terms: D004334:Drug Administration Schedule; D016903:Drug Monitoring; D006801:Humans; D010349:Patient Compliance; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D013997:Time Factors
chemical_list: D004364:Pharmaceutical Preparations