Table 2.
Adherence and persistence outcomes
| Study (country) | Follow-up period (months) | Adherence | Persistence | Adherence outcomes (I vs C) | Persistence outcomes (I vs C) |
|---|---|---|---|---|---|
| Informational patient programs | |||||
| Elkjaer et al (Denmark and Ireland)18 | 12 | The compliance questionnaire included five questions with dichotomized answers: easy access to prescription, ability of relapse recognition, following the medical doctor’s advice, ability to self-initiate acute treatment, and adherence to 5-ASA treatment. In Denmark, patients’ answers regarding 5-ASA refill were compared with results from the e-prescription pharmacy database | Denmark: 73% vs 42% (P=0.005) Ireland: 73% vs 29% (P=0.03) |
NR | |
| Homer et al (UK)7 | 4 | Adherence was defined as: “the extent to which the patient’s behavior matches agreed recommendation from the prescriber” | – | 90% vs 69% (P=0.06) | NR |
| Lai et al (Malaysia)24 | 12 | Adherence was defined as the average percentage of participants who were both persistent (continued bisphosphonate therapy) and compliant (took medication in the correct manner on the scheduled day). Pill count (by counting the number of tablets left at each visit) was used to measure adherence | Persistence (defined as the time in days from the date of the first dose of bisphosphonate until discontinuation of treatment) was obtained from supply records, using the pharmacy information system | 97.70% vs 96.46% (P=0.322) | 87.0% vs 89.8% (P=0.481) |
| Montori et al (USA)9 | 12 | To assess medication adherence at 6 months, patients were telephoned and asked Haynes’ single-item adherence question (“Have you missed any of your pills in the last week?”). Pharmacy records were obtained to assess adherence and persistence | Persistence was estimated using proportion of patients who had ≥80% adherence | 100% vs 98.20% (P=0.09) | 170 (range: 30–180) days vs 180 (range: 28–180) days (P=0.38) |
| Moss et al (USA)19 | 6 | Adherence was calculated based on refill data from pharmacies according to Steiner’s formula. Only patients with adherence >80% were considered to be adherent | – | 67% vs 50% (P=0.3) | NR |
| Nielsen et al (Denmark)17 | 24 | Adherence was defined as patients taking their medicine correctly at the appropriate time; patients who changed to another osteoporosis drug were considered to be adherent. Data on adherence were obtained via self-completed questionnaires | – | 92% vs 80% (P=0.006) | NR |
| Shu et al (USA)25 | 3 | Adherence was measured as MPRb. A patient who consistently filled prescriptions and had medication available for each day was 100% adherent | – | 87.60% vs 88.80% (P=0.60) | Not used as it was not possible to determine the effect size, using the data given |
| Solomon et al (USA)26 | 12 | Adherence was measured as MPRb. Pharmacy claims data from the collaborating state run pharmacy benefits program was used to calculate the MPR | – | 49% vs 41% (P=0.07) | NR |
| Behavioral patient programs | |||||
| Heilmann et al (USA)27 | 6 | Adherence was defined as a MPRb of at least 80% | Medication persistence was defined based on the last medication purchase prior to the 365-day cutoff date. If the days’ supply, multiplied by 1.2 was equal to or greater than the number of days between the final prescription purchase and the cutoff date, then medication use was considered persistent. A factor of 1.2 was used to allow for an adherence rate of less than 100% but at least 80% | 46% vs 28% (P=0.007) | 54% vs 45% (P=0.19) |
| Ting et al (USA)28 | 12 | Pharmacy refill adherence, defined as the percentage of the number of doses dispensed divided by the number of doses prescribed for the period of time between study visits and pharmacy refill dates, with pharmacy refill information serving as primary measure of medication adherence. Patients with adherence >80% were considered adherent | – | 37% vs 27% | NR |
| Combined patient programs | |||||
| Cook et al (USA)29 | 6 | Adherence was defined as months of treatment completed. When participants reported adherence, RNs assessed what percent of the past month’s doses were taken as prescribed; Patients with adherence ≥80% were considered adherent | – | 88% vs 57% (P<0.001) | NR |
| Moshkovska et al (UK)30 | 12 | Nonadherence, based on analysis of urine samples, was defined as: • Complete nonadherence: undetectable (0 lg/mL) levels of 5-ASA or N-acetyl-5-ASA. • Partial nonadherence: 5-ASA <30 lg/mL and N-acetyl-5-ASA <90 lg/mL • Adherence: 5-ASA ≥30 lg/mL and N-acetyl-5-ASA ≥90 lg/mL In order to focus on identifying factors determining full adherence, partial and complete nonadherence were subsequently combined to form a single category for comparison with complete adherence |
– | 76% vs 32% (P=0.001) | NR |
| Sewerynek et al (Poland)31 | 12 | The refill adherence was measured as MPRb. Patients with adherence >80% were considered adherent | Persistence was defined as the time in days from the date of prescription to the “run out” date in the treatment period. Patients were defined as “persistent” until a gap of >90 days was reached between the end of one prescribed drug series and the date of subsequent prescription; or until the patient switched to another bisphosphonate; or had a refill gap >30 days between the end of one prescription series and the beginning of the subsequent one | Educational group: 75.71% vs 54.03% Biochemical information group: 68.29% vs 54.03% Nurse assistance group: 71.18% vs 54.03% |
Educational group: 269.72 (SEM 26.95) days vs 197.00 (SEM 26.91) days Biochemical information group: 249.19 (SEM 29.04) days vs 197.00 (SEM 26.91) days Nurse assistance group: 259.71 (SEM 25.10) days vs 197.00 (SEM 26.91) days |
| Stockl et al (USA)32 | 8 | – | Discontinuation was defined as a gap of >30 days between the depletion date (fill date + number of days’ supply) for the last filled prescription and the end of the postidentification period | NR | 89.30%a vs 59.40%a (P<0.001) |
| Stockl et al (USA)8 | 8 | – | Medication persistence was defined as the number of days on therapy until a gap of >30 days Medication discontinuation defined as the gap of >30 days past the end of supply date for the last filled prescription and the end of the “Post” period |
NR | 219.80 (SD 80.30) days vs 176.50 (SD 92.00) days (P<0.001) 92.30%a vs 71.80%a (P<0.001) |
| Tamone et al (Italy)33 | 18 | – | Persistence was defined as the number of patients continuing treatment until the end of the 18-month course | NR | 85.60% vs 77.40% (P=0.006) |
| Tan et al (USA)34 | 12 | – | Medication persistence was referred to the duration of time from initiation to discontinuation of therapy, while discontinuation was defined as failing to obtain any MS medication within 60 days after the depletion of the previous supply | NR | 306.10 (SD 84.10) days vs 246.90 (SD 129.60) days (P<0.001) |
Notes:
a
Persistence rate was calculated from the discontinuation rate using the formula: persistence rate =100 - discontinuation rate.
b
MPR was defined as the number of days for which medication was available divided by number of days in the follow-up period.
Abbreviations: ASA, aminosalicylic acid; C, control group; I, intervention group; MPR, medication possession ratio; MS, multiple sclerosis; NR, not reported; RN, registered nurse; SD, standard deviation; SEM, standard error of mean.