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Table 2 Summary of the 30 studies included

From: Effect of drug reminder packaging on medication adherence: a systematic review revealing research gaps

Number Lead author Design n Duration Intervention Drug reminder packaging Outcomes Effect Methodological quality Completeness of information
1 Ascione[30] CCT 158 n.d. Drug reminder packaging, counseling n.d. A: Self-report*: Unclear Strong 0.13
2 Azrin [31] CCT 39 2 m a. Drug reminder packaging, counseling with family member vs Multicompartment adherence aid A: Pill count*: a. vs baseline: 95.03 vs 76.24 (P < 0.05, Ø CI) Strong 0.13
b. Drug reminder packaging, counseling vs    b. vs baseline: 92.01 vs 69.52 (P < 0.01, Ø CI)
c. Psychoeducational condition    c. vs baseline: n.s.
C: Symptoms checklist 90-R: n.s.
3 Becker [32] CCT 180 12 m Drug reminder packaging Multidrug punch card A: Pill count, self-report, BP: n.s. Moderate 0.38
C: BP: n.s.
4 Binstock [33] CCT 112 12 m a. Counseling vs n.d. A: Self-report: a., b., c.: n.s. Weak 0.25
b. Drug reminder packaging, counseling vs   C: sBP*, dBP*: b. vs a.: 133/80 mmHg vs 148/89 mmHg (P < 0.01, Ø CI)
c. Drug reminder packaging, counseling, other aids vs other interventions    c. vs a.: 134/84 mmHg vs 148/89 mm Hg (P < 0.01, Ø CI)
b. vs c.: n.s.
5 Crome (1980) [34] CCT 26 10 d Drug reminder packaging Multicompartment adherence aid A: Pill count: n.s. Weak 0.25
6 Crome (1982) [35] CCT 78 4 w Drug reminder packaging Multidrug punch card A: Pill count: n.s. Weak 0.25
7 Eshelman[36] CCT 100 n.d. Drug reminder packaging n.d. A: TDM*: ‘Adherent’ patients: 97% vs 69% (P < 0.05, Ø CI) Moderate 0.13
Pill count: n.s.
Self-report: Unclear
8 Fairley[37] RCT 43 5 m Drug reminder packaging, counseling, other aids Multicompartment adherence aid A: Self-report*: Total Morisky score: 3.3 vs 2.9 (P = 0.006, Ø CI) Moderate 0.13
  Rate of patients with a Morisky score of 0: 29% vs 49% (P = 0.04, Ø CI)
C: CD4 cell count, viral load: n.s.
9 Henry[38] CCT 119 10 d Drug reminder packaging, counseling, other aids Multidrug punch card A: Pill count + self-report: n.s. Strong 0.25
C: 13C-UBT: n.s.
10 Huang (TRACE) [39] RCT 184 2 m Drug reminder packaging Multicompartment adherence aid A: Pill count, self-report, TDM: n.s. Moderate 0.38
11 Huang (VITAL) [39] CCT 297 Unclear Drug reminder packaging (multidrug punch card vs multicompartment adherence aid) Multidrug punch card, multicompartment adherence aid A: Pill count*: Patients who took >90% of pills: 93% vs 87% (P = 0.05, Ø CI) Moderate 0.38
Self-report*: Positive answer to question ‘forgot to take pills’: 21 % vs 31 % (P = 0.05, Ø CI); self-report total score: n.s.
TDM: n.s.
12 Lee JK[40] RCT 200 14 m Drug reminder packaging, counseling, regular follow-up Multidrug punch card A: Pill count*: 95.5 vs 69.1 (P < 0.001, Ø CI) Strong 1.0
C: sBP*: Drug reminder packaging vs baseline: -6.9 mmHg (P = 0.005, CI -10.7- (-3.1) mm Hg)
dBP*: Drug reminder packaging vs baseline: -2.5 mm Hg (P = 0.04, CI -4.9-(-0.2) mm Hg)
LDL-C*: Drug reminder packaging vs baseline at 8 m: -4.8 mg/dl (P = 0.001, CI -7.8-(-1.9) mg/l)
Drug reminder packaging vs baseline at 14 m: n.s.
13 Lee M[41] RCT 125 14 d Drug reminder packaging, counseling, other aids Multicompartment adherence aid A: Pill count*: ITT1 (patients unavailable for follow-up took 100% [cg] or 0% [ig] of drugs): Weak 0.25
No. of patients with >60% of pills taken: n.s.
Patients with > 90% of pills taken: 87% vs 71% (P < 0.05, Ø CI)
ITT2 (patients unavailable for follow-up took 0% [cg + ig] of drugs):
Patients with >60% of pills taken: 94% vs 78% (P < 0.05, Ø CI)
Patients with > 90% of pills taken: 87% vs 59% (P < 0.01, Ø CI)
14 MacDonald[42] RCT 165 3 m Drug reminder packaging, counseling Multicompartment adherence aid A: Unclear - Weak 0.25
15 Maier[43] RCT 2,081 6 m Drug reminder packaging Multicompartment adherence aid C: HbA1C*: -0.74% vs -0.53% (P < 0.0001, Ø CI) Strong 0.13
16 McPherson-Baker[44] CCT 42 5 m Drug reminder packaging Multicompartment adherence aid A: MRC*: 75.8% vs 39.3% (Ø P, CI) Weak 0.13
  Drug reminder packaging vs baseline: 75.8% vs 46.8% (P < 0.01, Ø CI)
Appointment keeping*: 76.1% vs 73.3% (Ø P, CI)
  Drug reminder packaging vs baseline: 76.1% vs 56.7% (P < 0.05, Ø CI)
C: (Proxies for adherence)  
Mean hospitalizations*: 0.33 vs 1.04 (P < 0.05, Ø CI)
Opportunistic infections*: Reduction with increased medication intake (Ø numbers given, P < 0.05, Ø CI)
17 Miaskowski[45] CCT 174 6 w Drug reminder packaging, counseling, other aids Multicompartment adherence aid C: Pain reduction*: Relieve in average, worst and least pain: Ø numbers given (P < 0.0001, Ø CI) Moderate 0.25
Appropriate prescriptions*: Patients with appropriate opioid analgesic prescriptions vs baseline: 37.0% vs 28.3% (P = 0.008, Ø CI)
Change in total amount of opioids prescribed and taken: Prescribed: Ø numbers given (P < 0.0001, Ø CI)
Taken: Ø numbers given (P < 0.001, Ø CI)
18 Murray [46] CCT 36 6 m Drug reminder packaging Unit-of-use packaging A: Pill count*: 92.6 vs 79 (P < 0.0001, Ø CI) Weak 0.38
Self-report: No. of patients reporting all medication taken: 9 vs 8 (Ø P, CI)
19 Nochowitz[47] Pre-, post-cohort 14 3 m Drug reminder packaging, other aids Multicompartment adherence aid A: Pill count (+/- self-report if pills were not available): n.s. Moderate 0.38
C: INR*: Sub-therapeutic INR values (<2) vs baseline: 35% vs 60% (P = 0.04, Ø CI)
Time spent in therapeutic range vs baseline: 56% vs 32% (P = 0.03, Ø CI)
20 Park[48] CCT 61 2 w Drug reminder packaging ± organizing chart, factorial Multicompartment adherence aid A: Electronic self-report: Unclear Weak 0.13
21 Peterson [49] RCT 53 4 m Drug reminder packaging, counseling, other aids Multicompartment adherence aid A: MRF*: ‘Adherent’ patients: 88% vs 50% (P < 0.01, Ø CI) Moderate 0
TDM*: Patients within therapeutic range vs baseline: 88% vs 48% (P < 0.005, Ø CI)
Appointment keeping: n.s.
C: Seizure frequency*: Frequency of seizures vs baseline: 2.5 vs 6 (P < 0.01, Ø CI)
22 Rheder [50] CCT 100 3 m Drug reminder packaging ± counseling, factorial Multicompartment adherence aid A: Pill count*: No. of patients who took ≥95% of pills: Drug reminder packaging ± mi > mi, Ø numbers given (P < 0.01, Ø CI) Weak 0.63
C: BP*: Drug reminder packaging + mi vs baseline: Ø numbers given (P < 0.02, Ø CI)
Drug reminder packaging vs baseline: n.s.
23 Schneider [51] RCT 85 12 m Drug reminder packaging Multidrug punch card A: MPR *: 0.93 vs 0.87 (P = 0.039, Ø CI) Moderate 0.5
  Patients with their prescription refilled on-time (± 5 d): 80.4% vs 66.1% (P = 0.012, Ø CI)
C: dBP*: No. of patients with decreased dBP at 12 m: 12 vs 4 (P = 0.031, Ø CI)
sBP: n.s.
Absolute change in BP: n.s.
Long-term outcome measures: n.s.
24 Simmons [52] RCT 68 8 m Drug reminder packaging (Multi-)drug punch card C: dBP*: -5.8 mmHg vs 0.1 mmHg (P = 0.0041, Ø CI) Moderate 0.13
sBP: n.s.
HbA1C*: -0.95% vs -0.15% (P = 0.026, Ø CI)
H: Usability*: 77% vs 27% (P < 0.001, Ø CI)
25 Skaer (NIDDM) [53] CCT 258 12 m Drug reminder packaging ± rr, factorial Unit-of-use packaging A: MPR* Drug reminder packaging vs cg: 0.71 vs 0.58 (P ≤ 0.05, Ø CI) Weak 0.33
rr + drug reminder packaging vs cg: 0.87 vs 0.58 (P ≤ 0.05, Ø CI)
rr + drug reminder packaging vs drug reminder packaging: 0.87 vs 0.71 (P ≤ 0.05, Ø CI)
E: Drug reminder packaging vs cg:
Prescription expenditure*: +$74.09 (P ≤ 0.05, Ø CI)
All other expenditure: n.s.
  rr + drug reminder packaging vs cg:
Prescription expenditure*: +$124.86 (P ≤ 0.05, Ø CI)
Physician expenditure*: -$66.79 (P ≤ 0.05, Ø CI)
Laboratory expenditure*: -$18.05 (P ≤ 0.05, Ø CI)
Hospital expenditure*: -$107.69 (P ≤ 0.05, Ø CI)
Total expenditure*: -$67.67 (P ≤ 0.05, Ø CI)
(per capita)
26 Skaer (BP) [54] CCT 304 12 m Drug reminder packaging ± rr, factorial Unit-of-use packaging A: MPR* Drug reminder packaging vs cg: 0.67 vs 0.56 (P ≤ 0.05, Ø CI) Weak 0.33
  rr + drug reminder packaging vs cg: 0.79 vs 0.56 (P ≤ 0.05, Ø CI)
  rr + drug reminder packaging vs drug reminder packaging: 0.79 vs 0.67 (P ≤ 0.05, Ø CI)
E: Drug reminder packaging vs cg:
Prescription expenditure*: +$48.17 (P ≤ 0.05, Ø CI)
All other expenditure: n.s.
  rr + drug reminder packaging vs cg:
Prescription expenditure*: +$104.39 (P ≤ 0.05, Ø CI)
Physician expenditure*: -$78.41 (P ≤ 0.05, Ø CI)
Hospital expenditure*: -$89.54 (P ≤ 0.05, Ø CI)
Laboratory expenditure: n.s.
Total expenditure*: -$75.28 (P ≤ 0.05, Ø CI)
(per capita)
27 Solomon[55] CCT 372 7 d Drug reminder packaging ± videotape ± telephone interview, factorial Unit-of-use packaging A: Self-report (non-compliance score)*: Drug reminder packaging vs cg: 30.2 vs 50.7 Moderate 1.0
(P < 0.001, Ø CI)
Drug reminder packaging + videotape vs cg: 5.5 vs 11.1 (P < 0.001, Ø CI)
28 Valenstein [56] RCT 118 12 m Drug reminder packaging, counseling, other aids Multidrug punch card A: MPR*: At 6 m: 0.91 vs 0.64 (P < 0.0001, Ø CI) Moderate 0.17
At 12 m: 0.86 vs 0.62 (P < 0.0001, Ø CI)
CAM*: At 6 m: 26% vs 9% (P = 0.0003, Ø CI)
(MPR + self-report + TDM)
  At 12 m: 17% vs 9% (P = 0.06, Ø CI)
C: Psychiatric symptoms: n.s.
H: Patient satisfaction, quality of life: n.s.
29 Ware [57] CCT 84 3 m Drug reminder packaging, counseling Multidrug punch card A: Self-report + pill count*: Patients taking all prescribed doses: Weak 0.38
  At discharge: 86.7% vs 66.7% (P = 0.03, Ø CI)
At 10 d: 69% vs 41% (P = 0.02, Ø CI)
At 1 m: 64.4% vs 38.5% (P = 0.03, Ø CI)   
At 2 m: 57.8% vs 28.2% (P = 0.01, Ø CI)
At 3 m: 48.9% vs 23.1% (P = 0.03, Ø CI)
30 Winland-Brown [58] CCT 61 6 m Drug reminder packaging Multicompartment adherence aid A: Pill count: n.s. Weak 0.13
C: BP, INR, TDM, mood stabilization, HbA1C: Not reported
Physician visits: Mean (per patient) vs baseline: 1.5 vs 1.5 (Ø P, CI)
Hospital admission: No. of patients vs baseline: 7 vs 4 (Ø P, CI)
Home visit: No. of patients vs baseline: 0 vs 0 (Ø P, CI)
Transition to a higher level of care: Not reported
  1. The 13 additional studies compared to previous reviews [1820] are designated in bold. * indicates statistically significant outcomes.
  2. 13C-UBT, 13 C-urea breath test; A, adherence outcome; (s, d)BP, (systolic, diastolic) blood pressure; C, clinical outcome; CAM, composite adherence measure; CCT, controlled clinical trial; cg, control group; CI, confidence interval; d, days; E, economic outcomes; H, humanistic outcomes; HbA 1C , glycated hemoglobin; ig, intervention group; INR, international normalized ratio; LDL-C, low-density lipoprotein cholesterol; m, months; mi, multiple interventions; MRC, medication refill compliance; MRF, medication refill frequency; No., number; n.s., not significant; RCT, randomized controlled trial; rr, refill reminder; TDM, therapeutic drug monitoring; w, weeks.