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. 2011 Sep 23;5:441–463. doi: 10.2147/PPA.S23780

Table S1.

Measurement of compliance – electronic monitoring studies

Study group Design/cohorts Endpoint Patient/setting Study year Findings
Granstrom10 Retrospective observational
  1. E lectronic medication monitor data

  2. Chart review. Subjects were blinded from the purpose of the monitor. Single cohort: pilocarpine (TID)

See description of endpoints below in Norell/Granstrom 56 of 82 subjects from Norell16 who were followed for 2 years before and after the electronic monitor observation period Not specified Compared with those having no progression, those with progression of visual field defects during the 2-year pre-monitor period had a lower rate of “goodintermediate” (50%) vs “poor” compliance (58%) during the 20-day monitor assessment. In the noninterventional group (n = 26) followed for 2 years after monitor observation, those with progression of visual field defects, in the post-monitor period had a higher rate of “good-intermediate” (63%) vs “poor” compliance (30%) observed at the time of the monitor. Neither finding was significant. There was a statistically significant association between type of glaucoma, stage of visual field defects, and mean IOP. When these factors were adjusted for, the difference in proportion of patients with visual field defect progression in those with “good” vs “poor” compliance was reduced for both 2-year pre- and post-monitor periods
Hermann27 Prospective observational. Electronic medication monitor data. Subjects were randomly assigned to masked (ie, blinded) and unmasked monitoring. Random assignment to BID or TID dosing. Single cohort: brimonidine Over 4 weeks,
  1. Number of recorded application events per 24-hour period

  2. Time interval between doses

  3. Ratio of recorded to intended dose events (adherence)

  4. Proportion of time for which recorded dose was not exceeding intended dose by >3 hours (coverage)

36 subjects who were 18+ years with diagnosis of POAG or OHT, prescribed brimonidine BID to TID at university glaucoma clinic [Greece] Not specified
  1. BID mean = 1.47 (SD = 0.3), TID 1.92 (0.4) Sig

  2. BID 17.5 (4.4) hours, TID 13.2 (2.5) hours Sig

  3. BID 73.3% (13%), TID 64.0% (12%) Sig

  4. BID 71.8% (12%), TID 69.3% (9.5%) NS

Differences between means of masked vs unmasked monitoring for 1–4 were not significant when stratified by regimen (BID, TID)
Hermann28 Prospective observational. Electronic medication monitor data. All subjects were masked from purpose of the monitor. Random assignment to BID or TID dosing. Single cohort: brimonidine Over 4 weeks,
  1. Number of recorded application events per 24-hour period

  2. Time interval between doses

  3. Ratio of recorded to intended dose events (adherence)

  4. Proportion of time for which recorded dose was not exceeding intended dose by >3 hours (coverage)

  5. Amount of medication used per dosing event

  6. Mean number of drops applied per dosing event

75 subjects who were 18+ years with diagnosis of OAG, angle closure or OHT, receiving topical glaucoma therapy [France] Not specified
  1. BID mean = 1.44 (SD = 0.4), TID 1.86 (0.5) Sig

  2. BID 18.5 (5.9) hours, TID 14.8 (7.1) hours Sig. 35% of all dosing intervals in BID group and >20% in TID group were >16 hours

  3. BID 72.2% (19%), TID 62.1% (16%) Sig

  4. BID 69.9% (14%), TID 67.2% (15%) NS

  5. Treat 1 eye 69 (3.1) mg, treat both eyes 97 (3.3) mg Sig

  6. Treat 1 eye 1.7 (0.7), treat both eyes 2.4 (1.5) Sig. On average 20% of medication was wasted due to using >1 drop per eye per dosing

Kass23,24 Prospective observational
  1. E lectronic medication monitor data

  2. Post-monitor subject interview

  3. Pre-monitor physicianpredicted estimate of compliance

  4. W eight difference of vial between pre- and post-monitor visits

  5. Daily log of compliance [n = 32 subset sample] for additional 30-day period. All subjects were masked from purpose of the monitor. Single cohort: pilocarpine

  1. Percentage of doses taken as recorded by the monitor over 30 days

  2. One or more questions on compliance behavior at the end of the 30-day period

  3. E stimated number of doses that subject would omit over next 30 days

  4. Pre- vs post-observation difference in vial weight

  5. Subject daily diary of administration times

184 subjects who were 18+ years, currently prescribed pilocarpine QID for IOP reduction, from private practices of university faculty [Washington in US] 1981–1984
  1. For all subjects, mean of 76.0% (SD = 24.3%) of prescribed doses. 15.2% of all patients took < 50% of prescribed doses, 34.2% took < 75% of doses.22 Mean rate of compliance was higher (87.6% [27.8%] Sig) in the 24-hour period preceding the return appointment than over the entire 30-day observation period.22 IOP on day 30 return visit did not significantly correlate with compliance

  2. Subjects reported that they were taking a mean of 97.1% (5.9%) of prescribed doses. Correlation between patient-reported compliance and monitor data was modest (r = 0.203) Sig23

  3. Mean physician estimate of compliance was 79.4% (15.9%). Correlation between physician estimates of compliance and medication monitor estimates was modest, with a correlation coefficient of r = 0.20 Sig23

  4. Modest correlation (r = 0.18) Sig occurred between vial weight difference and monitor estimates23

  5. Mean reported rate of compliance was 98.9% (1.8%). Correlation between daily log and monitor data was modest (r = 0.24, NS)23

Kass25 Prospective observational. Electronic medication monitor data. All subjects were masked from purpose of the monitor. Single cohort: timolol (BID, with or without other agents) Compliance was defined as the percentage of timolol doses taken, as recorded by the monitor over 30-day period 110 subjects who were 18+ years, prescribed timolol BID for IOP reduction, from private practices of university faculty [Washington in US] 1984–1985 The entire group administered a mean of of 82.7% (SD = 19.0%) of prescribed doses. 8.2% of all patients took less than 50% of prescribed doses, and 27.3% took < 75% of doses. 60 of the 110 patients were receiving pilocarpine or another agent along with timolol. The rate of compliance with timolol was lower among patients receiving timolol alone vs those receiving timolol plus another agent NS
Norell-Granstrom1622 Prospective observational
  1. E lectronic medication monitor data

  2. Post-monitor patient interview

  3. Post-monitor physician and assistant estimates of compliance

Only findings prior to second, 20-day interventional phase of study are reported here. All subjects were masked from purpose of the monitor. Single cohort: pilocarpine (TID)
  • 1A) Number of days where <3 doses were self-administered over 20-day period

  • 1B) Proportion of missed doses (of 60 possible) over 20 days

  • 1C) Proportion of extra doses (of 60 possible) over 20 days

  • 1D) Proportion of time over 20-day period for which scheduled dosing time was exceeded

  • 2) Immediate post-monitor subject estimate of compliance during past 7 days compared with medication monitor data

  • 3) Immediate post-monitor physician and assistant estimates of estimates of compliance independent of knowledge from 1) and 2) above

82 subjects, aged 56–90 years, treated at eye clinic at Huddlinge University Hospital, with POAG, visual defects, cupping, IOP 21+ mmHg, visual acuity 2/60, and currently using pilocarpine TID [Sweden] 1977–1978
  • 1A) Patients missed at least 1 dose during 23% of all days. Of these, 19% occurred at the 1st, 54% at the 2nd, and 27% at the 3rd scheduled dose during the day

  • 1B) 10% of the doses prescribed were missed.16 Patients missed at least 1 dose during 23% of all days.17 Of all 60 expected doses, 59% of patients missed 0%–9% (had good compliance), 20% missed 10%–19% (had intermediate compliance), and 20% missed 20+% (had poor compliance)

  • 1C) 1% of doses were extra doses16

  • 1D) For a median of 17.2% (range 3%–8%) of the observed time, the time since the previous dose had exceeded 8 hours16

  • 2) 4% of patients said they missed 2+ doses over past week, compared to medication monitor results showing that 33% missed 2+ doses18

  • 3) Correlation between physician estimates of compliance and medication monitor estimates was poor, with a correlation coefficient of r = 0.19 NS

Robin26 Prospective, single-site, open-label, non-randomized, parallel design. Electronic medication monitor data. Subjects were not masked from purpose of the monitor. Cohorts: prostaglandin (QD) as monotherapy (1-drug group), prostaglandin with an adjunctive medication (2-drug group) Over a 60-day observation period
  1. Over/underadherence of the number of doses per 24-hour period, compared to nominal dosing: adherers (0–2 errors), marginal (3–5 dosing errors), and poor (>5 errors)

  2. Proportion of time for which interval between doses was <2 hours more than nominal dosing interval (coverage)

  3. Interval between doses (interdose interval)

  4. Number of doses divided by the number of days in study, times the prescribed dosing frequency (% of doses taken)

62 subjects at a private, subspecialty glaucoma practice, 18+ years with OAG or OHT, stable IOP for 30+ days, using either a single prostaglandin or prostaglandin plus adjunctive agent Not specified
  1. Overall, 20% of all subjects were in the poor category. For subjects in the 1-drug group, only 3.3% were in the poor category. For subjects in the 2-drug group, 10.0% were in the poor category for the prostaglandin and 30.0% were in the poor category for adjunctive therapy

  2. For the prostaglandin, the mean coverage was 97.2% (SD = 6.1%). It was similar in both the 1-drug group (97.5% [3.9%]) and the 2-drug group (96.8% [6.2%]). For adjunctive medications, the mean coverage was slightly less: 93.0% (8.3%)

  3. For the prostaglandin, the mean interval between doses was 24.4 (1.2) hours. When stratified by number of medications, the 2 groups were similar, 24.3 (1.2) hours for the 1-drug group vs 24.4 hours (1.3) for the 2-drug group. For adjunctive medications, the mean interval between doses was 22.7 (2.1) hours for QD dosing, 12.4 (1.4) hours for BID dosing, and 8.2 (0.2) hours for TID dosing

  4. For the prostaglandin, subjects took 97.0% (6.7%) of doses prescribed. The proportion of doses taken was similar when stratified by 1-drug [96.5% (4.7%)] or 2-drug [97.5% (8.2%)] groups. For the adjunctive medications (2-drug subjects only), subjects took 99.9% (13.0%) of doses prescribed

Abbreviations: BID, twice daily; IOP, intraocular pressure; NS, not significant at 95% confidence; OAG, open-angle glaucoma; OHT, ocular hypertension; POAG, primary open-angle glaucoma; QD, once daily; QID, 4 times daily; r, correlation coefficient; SD, standard deviation; Sig, significant at 95% confidence; TID, 3 times daily.