Definitions, cutpoints, and percent adherence/compliance across studies. Percent of adherent patients across studies that were included in the metaanalysis. Studies were placed into subgroups according to the method used to measure adherence. Scale and cutpoints used to rate adherence are also shown.
| Study | Outcome | Definition/scale | Cutpoint for Adherence/compliance | Adherence, % |
|---|---|---|---|---|
| Prescription claims | ||||
| Borah, et al11 | Adherence | MPR defined as the total days during followup period that the patient had a supply of the index medication/365 × 100. | MPR ≥ 80% | 48.6 for ETN |
| Cannon, et al12 | Adherence | MPR defined as the number of prescribed days of MTX during a course divided by total duration of days of the course. | MPR ≥ 80% | 84 full cohort |
| Li, et al13 | Adherence | PDC defined as the number of days covered with biologic/365 days. | PDC ≥ 80% | 32 for ETN |
| Harley, et al14 | Compliance | Compliance ratio-number of therapy administrations or filled prescriptions divided by the expected number. | Compliance ratio ≥ 80% | 68 for ETN |
| Tkacz, et al28 | Adherence | MPR defined as the sum of the days’ supply of the index treatment divided by the duration of treatment; PDC was also calculated, adjusted for double-counting of covered days. | MPR ≥ 80% | 61.8 for ETN |
| Jinnett and Parry29 | Adherence | The ratio of days in possession of a DMARD in a given year (no. days supplied with DMARD) divided by the no. days in the reference year, for individuals with at least 1 DMARD prescription fill in that year. | MPR ≥ 75% | 52.1 |
| Esposti, et al30 | Adherence | PDC = total mg of the drug prescribed/defined daily dose; total coverage (%) = sum of prescription coverage (days)/duration of the followup period (365 days) × 100. | > 80% of the followup period was covered by drug dispensation | 31 for ETN |
| Questionnaires | ||||
| van den Bemt, et al33 | Adherence | Questions on taking medications and missing doses (4-point scale, do not agree at all–agree very much). | CQR score ≥ 80% | 70 |
| Contreras-Yanez, et al15 | Adherence | Adherent was defined when either boxes 3 (almost always) or 4 (always) were filled for items 10, 11, and 12 (in the past 2 mos, I took my medication exactly at the days/day times/the precise amount indicated by my rheumatologist). | NA | 80.6 |
| Salt and Frazier16 | Adherence | Forgot to take, alter dose, stop taking, miss a dose, etc. Five-point scale; never to very often. | MARS-9RA scale ≥ 86% | 90.7 previous cutpoint |
| van den Bemt, et al2* | Adherence | Questions regarding taking medications and missing doses (4-point scale, 0 = strongly disagree, 3 = strongly agree). | CQR score ≥ 80% | 68 for CQR |
| Neame and Hammond17 | Adherence | I often do not take my medicines as directed (5-item scale: strongly disagree, disagree, neither agree nor disagree, agree, strongly, agree). Adherence was defined as strongly disagree or disagree. | NA | 91.8 |
| Treharne, et al18 | Adherence | How often they forget to take medications/miss/adjust a dose (5-point scale from very often to never). Adherent patient was defined as rarely or never miss a dose. | NA | 90.6, 80% cutpoint |
| Bluett, et al31 | Adherence | A classification of adherence was given if the injection was administered by the patient on the day agreed with the healthcare professional. | NA | 84.7 |
| Interview | ||||
| Tuncay, et al19 | Compliance | Questions regarding dose and timing (4-item scale: strictly, quite, not really, not at all). Compliant patients were defined as strictly or quite. | NA | 52.3 |
| Owen, et al20 | Compliance | Compliant patient claimed that they did not alter the dose of their medication from their prescriber instructions. | NA | 63.5 |
| Lee and Tan21 | Compliance | Did you take your antirheumatic tablets all of the time, most of the time, some of the time, or never? Adherence was defined as most or all of the time. | NA | 61.1 |
| Lorish, et al22 | Adherence | Missed at least 1 dose during the last mo (dose not taken within 4 h of the prescribed time). | NA | 77.5 |
| Viller, et al23 | Compliance | Do you always take your drugs exactly on time and at the dosage recommended? Four-point scale: not at all, not exactly, fairly exactly, exactly. Patients who answered yes, exactly to both questions were classified as compliant. | NA | 57 |
| Pullar, et al 24^ | Compliance | Noncompliance was defined as admission in interview. | NA | 96 |
| Pill count | ||||
| Brus, et al25 | Compliance | No. tablets taken divided by the no. tablets prescribed. | ≥ 80% was defined as high compliance | 87 |
| Pullar, et al^24 | Compliance | Pill count: compliant patients were defined as “returned tablet count indicating that more than 85% of the prescribed dose had been taken.” | Pill count ≥ 85% | 76 |
| MEM | ||||
| Park, et al26^ | Adherence | If a subject took an accurate no. doses on any given day, they were considered adherent. | NA | 95.4 |
| Waimann, et al32 | Adherence | The total no. days or weeks with the correct no. doses divided by the total no. monitored days, multiplied by 100. | Took DMARD as prescribed at least 80% of the time | 21 DMARD |
| Drug level | ||||
| Pullar, et al24^ | Compliance^ | Compliance was defined by phenobarbitone LDR = PB concentration divided by daily PB dose. | PB LDR ≥ 85% of the age-adjusted lowest value found in a group of 40 volunteers | 58 |
| Hill, et al27 | Adherence | Poor adherence was defined as PB LDR (the ratio of phenobarbitone blood levels to prescribed dose) less than 85% of that prescribed. | PB LDR ≥ 85% | 84 analysis1# |
↵# Analysis 1 included any patient who stopped taking the medication regardless of the reason. Analysis 2 included patients who stopped medication because of adverse events according to medical advice. We excluded analysis 2 because other studies included any patient as in analysis 1.
@ Participants used a 5-point scale (from very often to never) to answer the RAM scale questionnaire (how often they forget to take their medications). “Never” was considered as equivalent to a cutpoint of 100% and rarely to ≥ 75%.
↵^ Results were given as percent of nonadherent/compliant patients.
↵* This article used an interview and questionnaires to measure adherence. The interview included the following question: Do you sometimes decide to skip a dose or do you sometimes forget a dose? The possible answers were 1 (never), 2 (once a month), 3 (3 times a month), 4 (once a week), 5 (several times a week), and 6 (I never take this medicine). Response 4 (missed dose a week) was defined as the cutoff for nonadherence. Because this is an absolute and not a relative scale, this result was not used in the metaanalysis; rather, we used the result obtained by the questionnaire. MEM: medication and event monitors; MPR: medication possession ratio; MTX: methotrexate; PDC: proportion of days covered; DMARD: disease-modifying antirheumatic drug; LDR: level to dose ratio; PB: phenobarbitone; CQR: Compliance Questionnaires in Rheumatology; NA: not applicable; MARS: Medication Adherence Report Scale; RA: rheumatoid arthritis; ETN: etanercept; RAM: Reported Adherence to Medication.