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Table 3 Results of included studies

From: Interventions to increase adherence in patients taking immunosuppressive drugs after kidney transplantation: a systematic review of controlled trials

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
  1. C control group, CI confidence interval, EM electronic monitoring, I intervention group, ns not significant, NR not reported
  2. aUnless otherwise indicated, all values are group means of the last follow-up
  3. b p value for treatment by time interaction