Table BSummary of results for patient, provider, and systems interventions (KQ 1)

Clinical ConditionType of InterventionStrength of Evidence for Medication AdherenceNumber of Studies; n of Individuals (n Analyzed); ResultsStrength of Evidence for Other OutcomesNumber of Studies; n of Individuals (n Analyzed); Results
DiabetesCase management/collaborative care3335Low SOE of benefit for medication adherence3; 507 (507)

Varied measures and magnitude
Low SOE of benefit for HbA1C1; 58 (58)

1.2 percentage points difference
Education with social support36Insufficient for medication adherence1; 199 (189)

No stat sig difference
NANA
Health coaching37Insufficient for medication adherence1; 56 (49)

No stat sig difference
NANA
HyperlipidemiaCollaborative care35Insufficient for medication adherence1; 329 (117 on lipid-lowering meds)

No stat sig difference
NANA
Decision aids3840Insufficient for medication adherence2; 248 (98 + NR in 1 trial)

Variable self-report measures with variable outcomes
Low SOE of benefit for patient satisfaction1; 98 (98)

Variable self-report measures, some improvements for intervention group in specific areas
Education and behavioral support (telephone or mail)4145Low SOE of benefit for medication adherence5; 18,492 (9,411 + NR in 1 trial)

Variable measures (self-report, pharmacy refill) with variable outcomes
NANA
Multicomponent (education face-to-face with pharmacist + blister packaging)46Insufficient for medication adherence1; 159 (159)

Improved in intervention group over 6 months; outcome at risk of bias due to differing measurement frequency:
  1. Percentage adherence (95.5% vs. 69.1%)
  2. Percentage with ≥80% adherence (97.4 vs. 21.7)
Insufficient for LDL-C1; 159 (135)

No stat sig difference between groups
HypertensionBlister packaging47Low SOE of benefit for medication adherence and persistence1; 93 (85)

MPR: 6 percentage points difference between groups

Percentage of patients who had prescriptions refilled on time: 14.3 percentage points difference between groups
Insufficient for SBP + DBP; angina, MI, or stroke1; 93 (85)

No stat sig difference in change in SBP or DBP or in percentage of patients with reduced SBP, angina, MI, or stroke

29.8 percentage points difference in patients with reduced DBP at 12 months in intervention group
Insufficient for health care utilization: ED visits + hospitalizations1; 93 (85)

No stat sig difference between groups for either outcome
Case management4850Low SOE of benefit for medication adherence3; 516 (64 + NR in 2 studies)

Two of 3 RCTs with stat sig difference in adherence:
  1. MEMS ≥80% adherence: 46.8 percentage points more in experimental than control group
  2. MEMS adherence, mean: 11.3 percentage points higher in experimental group
Low SOE of benefit for SBP + DBP2; 214 (64 + NR in 1 study)

Difference in SBP: −8.5 to −14 mm Hg (range across studies)

Difference in DBP: −3.1 to −9.2 mm Hg (range across studies)
Collaborative care35,51,52Low SOE of no benefit for medication adherence3; 1,194 (785)

No stat sig differences between groups
NANA
Education (face-to-face with pharmacist)46,5355Low SOE of benefit for medication adherence; insufficient for persistence3; 348 (344) for adherence

Variable outcomes for adherence, some stat sig differences favoring intervention

1; 56 (53) for refilling meds on time

No stat sig difference between groups refilling meds on time
Moderate SOE of benefit for SBP2; 292 (268)
−6.4 or −8.9 mm Hg mean SBP difference
Insufficient2; 292 (268)
1.1 or −4.4 mm Hg mean DBP difference
Insufficient for quality of life1, 133 (NR)
No stat sig differences for sexual dysfunction, dizziness, and headaches
Low SOE of benefit for patient satisfaction1; 133 (130)
Stat sig improvement in 4 of 5 questions
Low SOE of benefit for hospital visits1; 133 (124)

0.08 fewer hospital visits in intervention group
Low SOE of benefit for contact withother health care providers1; 133 (124)

0.41 fewer visits in intervention group
Insufficient for ED visits1; 133 (124)

No stat sig difference
Education and behavioral support (telephone, mail, and/or video)43,5660Low SOE of benefit for medication adherence5; 6,996 (5,149 + NR in 2 studies)

Multiple variable outcomes
Two RCTs with stat sig difference in adherence showing 6 percentage points higher in intervention group from baseline to 6 months and greater adherence at 12 and 18 months; no numbers reported
Insufficient for SBP or DBP1; 299 (267)

No stat sig difference between groups in change from baseline to 6 months
Education with social support36Insufficient for medication adherence1; 199 (199)

No stat sig differences between groups at 12 months
NANA
Risk communication61Insufficient for medication adherence1; 89 (89)

No stat sig difference between groups at 3 months
NANA
Heart FailurePatient access to medical records62Insufficient for medication adherence1; 107 (NR)

No stat sig difference at 6 or 12 months
NANA
Case management63Low SOE of benefit for medication adherence1; 156 (156)

Difference in percentage points for med adherence: 6.6 to 6.8 (range)

Difference in percentage points for proportion with >80% adherence between groups: 15.7 to 16.3
Insufficient for all-cause hospital admission1; 156 (156)

No significant difference in multiple measures of all-cause readmission
Multicomponent pharmacist led64Low SOE of benefit for medication adherence1; 314 (314 for MEMS NR for MPR or self-report)

Difference in percentage points for taking medication (MEMS) at 9 months: 10.9
Difference in percentage points for adherence to timing (MEMS) at 9 months: 5.9
Difference in percentage points for MPR over 12 months: 4.2
No stat sig difference for self-report
Insufficient for quality of life1; 314 (NR)

No stat sig difference
Low SOE of benefit for patient satisfaction1; 314 (NR)

Difference of 0.3 on 12-point validated questionnaire
Low SOE of benefit for all-cause ED visits and all-cause ED + hosp1; 314 (314)

Difference of 0.52 mean all-cause ED visits and 0.69 mean all-cause ED + hosp between groups
Insufficient for health care utilization, including all-cause hospitalization, CV-related and HF-related events, costs1; 314 (314)

No stat sig difference
Reminder video and telephone calls65Low SOE of benefit for medication adherence1; 60 (50)

Difference of 17% to 27% comparing video and telephone to control in MEMS adherence over 8 weeks
Insufficient for quality of life1; 60 (42)

No stat sig difference
Myocardial InfarctionEducation and behavioral support66Low SOE of benefit for medication adherence; insufficient for persistence1; 907 (836)

Percentage points mean increase in adherence over 9 months: 4.3
Percentage points difference with ≥80% adherence: 6

No stat sig difference for persistence
NANA
AsthmaSelf-management6771Moderate SOE of short-term benefit in medication adherenceDifference in percentage points for adherence: 14 to 31Insufficient for pulmonary function and inflammation markers2; 152 (149)
No stat sig difference
Insufficient for symptom improvement5; 303 (300)
Varied measures and magnitude (inconsistent)
Low SOE of no benefit for quality of life4; 248 (245)
Varied measures and magnitude (consistent)
Shared or clinical decisionmaking72Low SOE of benefit for medication adherence1; 612 (612)

Difference in medication acquisition ratio for all asthma medications: 0.13 to 0.21
Low SOE of benefit for pulmonary function1; 612 (612)
Difference in FEV1 percentage points: 2.7 to 3.4
Low SOE of benefit for symptom improvement1; 612 (612)
Difference in mean equivalents of SABA canister equivalents acquired at 2 years between shared decisionmaking and usual care: 1.6
Low SOE of benefit for quality of life1; 612 (612)
Difference in subscale scores on 5-item Mini Asthma Quality of Life Questionnaire: 0.3–0.4
Low SOE of benefit for health care utilization1; 612 (612)
Difference of 0.3 to 0.4 fewer asthma-related visits per year
Asthma or COPDPharmacist or physician access to patient adherence information73,74Low SOE of no benefit for medication adherence2; 3,811 (3,596)

No stat sig difference
NANA
DepressionCase management33,48,7577Moderate SOE of benefit for medication adherence3; 508 (437)

Difference in percentage points for adherence or filling prescriptions over time: 9 to 15 (range across studies)
Moderate SOE of benefit for symptom improvement3; 508 (437)

Difference in CES-D scale: 7.0 to 9.4 (range across studies)
Mean difference in SCL-20 (0 to 4 range) scores between groups across 12 months: 0.08
Insufficient for self-reported disability1; 386 (315)

Varied measures, outcomes, time periods
Collaborative care7883Moderate SOE of benefit for medication adherence for telephone + in person; insufficient for telephone only; insufficient for depression + HIV patients3 (telephone and in person); 598 (598)

Difference in percentage points for adherence: 16.5 to 40.3 (range across studies)

No stat sig difference for depression + HIV patients or telephone collaborative care only
Low SOE of benefit for symptom improvement for major depression or moderate depression; insufficient for severe or minor depressionSevere depression: 2; 214 (214)
Minor depression: 1; 149 (149)
Moderate depression: 2; 156 (156)
Major depression: 1; 79 (79)

Varied measures, outcomes, time periods
Low SOE of benefit for patient satisfaction with antidepressants2; 370 (370)

Difference in percentage points in those rating antidepressants as helping somewhat to a great deal: 6.0 to 24.8 (range across studies)
Insufficient for health care utilization3; 598 (598)

Varied outcomes, time periods, and consistency
Insufficient for costs1; 228 (228)

No stat sig difference
Moderate SOE of benefit for patient satisfaction with quality of care3; 598 (598)

Difference in percentage points in those rating quality of care as good to excellent:
5.1 to 32.5 (range across studies) at 3 to 4 months, 16 at 6 months
Medication telemonitoring or telephone care84,85Insufficient for medication adherence2; 270 (255)

No stat sig difference
NANA
Reminders to nonadherent patients and lists of nonadherent patients to providers86Low SOE of benefit for medication adherence1; 9,564 (9,564)

Difference in percentage points for adherence: 1 to 3 (range across study)
NANA
GlaucomaMulticomponent intervention87Low SOE of benefit for medication adherence1; 66 (66)

Difference in adherence rate: 0.22
Insufficient for intraocular pressure1; 66 (66)

No stat sig difference
Multiple SclerosisCounseling (software-based telephone)88Low SOE of benefit for medication adherence1; 435 (367)
Difference in percentage points of patients who discontinued use of multiple sclerosis therapy: 7.5
NANA
Musculoskeletal DiseasesDecision aid89Insufficient for medication adherence, persistence, initiation of therapy1; 100 (100)

Varied outcomes and measures
Insufficient for patient satisfaction1; 100 (NR)

No stat sig difference
Case management90Insufficient for medication adherence1; 127 (127)

No stat sig difference
NANA
Virtual osteoporosis clinic91Low SOE of benefit for medication adherence1; 235 (211)

Difference in percentage points of women using osteoporosis medication at 13 months: 23.7
Insufficient for patient satisfaction1; 235 (211)

No stat sig difference
Multiple or Unspecified Chronic ConditionsCase management intervention9294Low SOE of no benefit for persistence3; 3,307 (3,269)

No stat sig difference
NANA
Outreach, education, and problem-solving (pharmacist led)95Insufficient for medication adherence1; 96 (75)

No stat sig difference
NANA

Abbreviations: CES-D scale = Center for Epidemiologic Studies-Depression scale; COPD = chronic obstructive pulmonary disease; CV = cardiovascular; DBP = diastolic blood pressure; ED = emergency department; FEV1 = forced expiratory volume at 1 minute; G = group; HF = heart failure; HbA1c = hemoglobin A1c; hosp = hospitalization; KQ = Key Question; LDL-C = low-density lipoprotein cholesterol; MEMS = medication event monitoring system; MI = myocardial infarction; MPR = medication possession ratio; NA = not applicable; NR = not reported; RCT = randomized controlled trial; SABA = short-acting beta agonists; SBP = systolic blood pressure; SCL-20 = Hopkins Symptom Checklist-20; SOE = strength of evidence; stat sig = statistically significant.

From: Executive Summary

Cover of Closing the Quality Gap: Revisiting the State of the Science (Vol. 4: Medication Adherence Interventions: Comparative Effectiveness)
Closing the Quality Gap: Revisiting the State of the Science (Vol. 4: Medication Adherence Interventions: Comparative Effectiveness).
Evidence Reports/Technology Assessments, No. 208.4.
Viswanathan M, Golin CE, Jones CD, et al.

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