Table 3 Results of included studies
Study | Adherence measure | Implementation adherence measurement (measurement time points) | Results for adherencea (I vs. C; p or 95%CI) | Clinical and other adherence outcomes | Results for other outcomesa (I vs. C; p or 95%CI) |
|---|---|---|---|---|---|
Annunziato 2015 | Standard deviation of tacrolimus blood levels (mean) | NR (median 8 measures) | 2.68 vs. 3.37; p = 0.32b | Episodes of rejection (n) | 3 vs.4; p > 0.05 |
Breu-Dejean 2016 | NR | Questionnaire (5 months) | 74.5 vs. 47.3%; p < 0.05 (5 months); p = NR (10 years) | Mortality | 12.7 vs.9.1%; p = 0. 35 |
– | – | – | Allograft survival | 69.1 vs.87.3%; p = 0.06 | |
Chisholm 2001 | Percent of patients taking ≥ 80% (monthly) | Prescription refill (monthly at each visit) | I > C; p < 0.05 for 6 of 12 months (months 6–8 and 10–12); p > 0.05 for 6 of 12 months (1–5 and 9) | Duration of compliance since transplant | 75 vs. 33.3%; p < 0.05 |
Mean doses taken | Prescription refill (monthly at each visit) | 96.1 vs. 81.6%; p < 0.001 | Time to first non-compliance (month) | 11; 95%CI 10–12 vs. 9; 95%CI 7–11 | |
Blood level within range (cyclosporine 250–400 ng/mL and tacrolimus 8–15 ng/mL) | Serum concentrations (monthly at each visit) | 64 vs. 48%; p < 0.05 (whole study period) | – | – | |
Chisholm 2013 | Mean doses taken | Prescription refill (baseline + every 3 months) | 89 vs. 79%; p < 0.01 | – | – |
De Geest 2006 | Patients taking < 98% and/or ≥ 1 drug holiday (no medication intake > 36 h for a twice daily dosing regimen, or > 60 h for a once daily dosing regimen) | EM (daily measurement over 9 months) | Decrease: I > C; p = 0.31 (3 month); p = 0.58 (9 months) | – | – |
Fennell 1994 | Mean doses taken | Pill count (4–6 weeks and 8–12 weeks) | Increase: 67% (azathioprine); 56% (prednisone) vs. 33% (azathioprine); 35% (prednisone); p b < 0.05% (azathioprine); p b < 0.02 (prednisone) | – | – |
Blood level within range (cyclosporine) | NR (4–6 weeks and 8–12 weeks) | I > C; p = 0.06 b (4–6 weeks); NR; ns (8–12 weeks) | – | – | |
Garcia 2015 | Non-adherent patients (questionnaire score < 12) | Questionnaire (immunosuppressant Therapy Adherence Scale, score 0–12, 3 months) | 14.5 vs. 46.4%; p = 0.001 | Mortality | 1.8 vs. 1.8%; p = 1.00 |
Mean sum score values | Questionnaire (immunosuppressant Therapy Adherence Scale, score 0–12, 3 months) | 11.82 vs.11.2; p = 0.001 | Acute reaction | 16.4 vs. 14.3%; p = 0.76 | |
Mean tacrolimus blood levels (ng/dL) | NR (at each outpatient visit up to the 3 months and were also assessed at 6 months and 1 year) | 8.74 vs. 8.78; p = 0.93 | Graft lose | 1.8 vs. 7.1%; p = 0.17 | |
Hardstaff 2003 | Number of patients showing adherence improvement | EM (first outpatient visit and after feedback, 3 months) | 6 vs. 5; NR (first outpatient visit) 6 vs. 2; NR (post intervention) | – | – |
Henriksson 2016 | Tacrolimus blood levels (mean) | NR (twice weekly over the first 3 months, once a week from then until 6 months, and once a month from 6 months to 1 year) | NR; p > 0.05 | Emergency hospital admissions | 22 vs. 31; p = 0.854 |
– | – | – | Rejection | 6 vs. 27; p = 0.054 | |
Joost 2014 | Daily adherence (Percentage of days with correct dosing) | EM (daily measurement) | 91 vs. 75%; p = 0.014 | Physical sum scale (SF-36) | I > C; p = 0.329 |
Patients with daily adherence ≥80% | 84 vs. 57%; p = 0.015 | ||||
Mean doses taken | 95 vs. 82%; p = 0.005 | Mental sum scale (SF-36) | I > C; p = 0.419 | ||
Patients taking ≥90% ≤ 110% of doses | 84 vs. 57%; p = 0.015 | ||||
Timing adherence (percentage doses taken within 6-h interval ± 3 h) | 95 vs. 94%; p = 0.142 | Anxiety scale (SF-36) | 4.74 vs. 4.33; p = 0.266 | ||
Timing adherence ≥ 80% | 97 vs. 86%; p = 0.110 | ||||
Patients without drug holidays (no intake > 48 h) | 81 vs. 43%; p = 0.001 | Depression scale (SF-36) | 2.89 vs. 2.64; p = 0.193 | ||
Mean doses taken | Pill count | 97 vs. 90%; p = 0.008 | |||
Patients taking ≥ 90 ≤ 110% of doses | 84 vs. 63%; p = 0.047 | ||||
No missed intake during the last 2 weeks | Self report (12 months) | 72 vs. 77%; p = 0.193 | |||
Fully adherent | Morisky questionnaire (12 months) | 63 vs. 63%; p = 0.695 | |||
Russel 2011 | Mean medication adherence score (0.5 if medication-dose was taken within 3 h of prescribed 12 h time frame; 0.25 if not within 3 h but 12 h; and 0 if not within 12 h) | EM (daily measurement over 6 months) | 0.88 vs. 0.77; p = 0.04 | – | – |
Tschida 2013 | Mean doses taken | Prescription refill | 87 vs. 83%; p < 0.0001 | Discontinuation (≥ 60 days without medications never followed by re-initiation within the study period) | 39 vs. 104; p < 0.0001 |
Number of medication gaps (≥ 60 days without medication in post-period but followed by re-initiation before end of post-period) | 29 vs. 53; p = 0.006 |