Table 2 Summary of the 30 studies included

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: HbA_1C*:

-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.

HbA_1C*:

-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, HbA_1C:

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