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- Closing the Quality Gap Series: Medication Adherence Interventions: Comparative Effectiveness
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- Research Review Sept. 11, 2012
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Executive Summary – Sept. 11, 2012
Closing the Quality Gap Series: Medication Adherence Interventions: Comparative Effectiveness
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Table of Contents
- Background
- Scope and Key Questions
- Methods
- Results
- Discussion
- Conclusions
- References
- Full Report
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Achieving the goal of quantitatively improving the quality and effectiveness of health care for all Americans requires both knowledge and tools. Although medical researchers have demonstrated many efficacious medical treatments to improve health outcomes, a recent Institute of Medicine report identified a disquieting discrepancy between present treatment success rates and those thought to be achievable.1 This gap has been attributed partly to barriers that providers face in implementing best practice guidelines.1,2 Patients' adherence to treatment, however, provides an additional explanation for the incongruity between recommended treatment and actual treatment outcomes.
Poor medication adherence is relatively common.3,4 Studies have shown consistently that 20 to 30 percent of medication prescriptions are never filled and that, on average, 50 percent of medications for chronic disease are not taken as prescribed.5,6
This lack of adherence to medications is not only prevalent, but also has dramatic effects on individual and population-level health.5,7-16 Nonadherence has been estimated to cost the U.S. health care system between $100 billion and $289 billion annually in direct costs.3,5,17-20 Strong evidence suggests that benefits attributable to improved self-management of chronic diseases could result in a cost-to-savings ratio of approximately 1:10.21-27
Scope and Key Questions
This review seeks to synthesize evidence regarding the efficacy and effectiveness of interventions to improve medication adherence among adults across a broad array of chronic conditions. This report is part of a larger initiative, the Closing the Quality Gap: Revisiting the State of the Science series. This series builds on the Agency for Healthcare Research and Quality (AHRQ) 2004–07 collection of publications, Closing the Quality Gap: A Critical Analysis of Quality Improvement Strategies, which summarized the evidence on quality improvement strategies for chronic conditions.28 This new series continues to summarize evidence on means to improve quality of care, but it focuses on selected settings, interventions, and clinical conditions. Our report addresses the comparative effectiveness of adherence intervention strategies, one keystone to improving the gap between potential and realized quality health care. The five Key Questions (KQs) that are the focus of this review are:
- Among patients with chronic diseases with self-administered medication prescribed by a provider, what is the comparative effectiveness of interventions aimed at patients, providers, systems, and combinations of audiences in improving medication adherence?
- Is improved medication adherence associated with improvement in patient outcomes?
- Among patients with chronic diseases with self-administered medication prescribed by a provider, what is the comparative effectiveness of policy interventions in improving medication adherence?
- Is improved medication adherence associated with improvement in patient outcomes?
- How do medication-adherence intervention characteristics (e.g., mode of delivery, intervention target, intensity) vary?
- To what extent do the effects of adherence interventions vary based upon their characteristics?
To what extent do the effects of adherence interventions vary based on differences in vulnerable populations?
What unintended consequences are associated with interventions to improve medication adherence?
The analytic framework we developed to guide the systematic review process is shown in Figure A.
Topic Refinement
Topics for the Closing the Quality Gap: Revisiting the State of the Science series were solicited from the leads of AHRQ portfolios (areas of research). Subsequently, the Evidence-based Practice Center (EPC) worked on clarifying the scope of the project. After we generated an analytic framework, preliminary KQs, and preliminary inclusion/exclusion criteria in the form of PICOTS (populations, interventions, comparators, outcomes, timing, settings), our KQs were posted for public comment on AHRQ's Effective Health Care Web site from March 11, 2011, to April 8, 2011. We revised the KQs as needed based on review of the comments and discussion with a five-member Technical Expert Panel (TEP), primarily for readability and greater comprehensiveness.
Literature Search and Review Strategy
To identify articles relevant to each KQ, we conducted targeted searches using MEDLINE®, Cochrane Library, and the Cochrane Central Trials Registry. (Appendix A of the main report lists search terms.) We reviewed our search strategy with TEP members and supplemented it as needed according to their recommendations. In addition, to avoid retrieval bias, we manually searched the reference lists of pertinent reviews on this topic to look for any relevant citations that might have been missed by our searches.
Two trained members of the research team independently reviewed each of the titles and abstracts. For each article that either or both reviewers chose to include based on the abstract review, two reviewers performed a full-text review for eligibility against our inclusion/exclusion criteria (Table A). During full-text review, if both reviewers agreed that a study did not meet the eligibility criteria, the study was excluded. Reviewers resolved conflicts by discussion and consensus or by consulting a third member of the review team.
For studies that met our inclusion criteria, a trained reviewer abstracted information into structured evidence tables; a second senior member of the team reviewed all data abstractions for completeness and accuracy.
Figure A. Analytic framework
Abbreviations: KQ = Key Question.
|Inclusion Criteria
|Exclusion Criteria
|Time period
|Length of followup
|Publication language
|Admissible evidence for Key Question 1 on patient-level, provider-level, or systems-level interventions (study design and other criteria)
|Admissible evidence for policy-level interventions (study design and other criteria)
Risk-of-Bias Assessment
Two independent reviewers assessed risk of bias (internal validity) for each study using predefined criteria based on those developed by AHRQ29 and specified in the RTI Item Bank.30 We resolved disagreements between the two reviewers by consulting an experienced member of the team.
Data Synthesis
For KQ 1, results are categorized by clinical condition. For KQs 2 and 3, results are categorized by intervention characteristics. We specified all nonmorbidity data a priori and elected, based on feedback from our TEP, to collect a comprehensive set of biomarkers and morbidity outcomes rather than make a priori judgments about which specific morbidity outcomes to include. For KQ 3, when appropriate data were available, we reported results from direct comparisons of different interventions. We did not attempt indirect comparisons, given the heterogeneity of usual-care comparators. We evaluated whether the collected data could be pooled by considering similarity of PICOTS. If three or more studies were similar (population, intervention, comparator, outcome), we considered conducting quantitative analyses (i.e., meta-analysis) of the data from those studies. Because quantitative analysis was not appropriate (due, for example, to heterogeneity, insufficient numbers of similar studies, or insufficiency or variation in outcome reporting), we synthesized the data qualitatively. For KQ 4, we intended to stratify our analyses and perform subgroup analyses when possible and appropriate. Planned stratifications or categories for subgroup analyses included disease type, intervention characteristics, racial and ethnic minorities, low-health-literacy groups, and the elderly.
Strength-of-Evidence Grading
We graded the strength of evidence for medication adherence, morbidity, mortality, and other long-term health outcomes for KQ 1 and KQ 2, for vulnerable subpopulations (KQ 4), and for harms (KQ 5) based on the guidance established for the EPC program.31 This approach incorporates four key domains: risk of bias (including study design and aggregate quality), consistency, directness, and precision of the evidence.
Definitions of the grades of overall strength of evidence31 are as follows:
- High: High confidence that the evidence reflects the true effect. Further research is very unlikely to change our confidence in the estimate of effect.
- Moderate: Moderate confidence that the evidence reflects the true effect. Further research may change our confidence in the estimate of the effect and may change the estimate.
- Low: Low confidence that the evidence reflects the true effect. Further research is likely to change our confidence in the estimate of the effect and is likely to change the estimate.
- Insufficient: Evidence either is unavailable or does not permit estimation of an effect.
We assessed the applicability of the evidence following guidance from Atkins and colleagues.32 We used the PICOTS framework to explore factors that affect or limit applicability.
We provide a summary of results by KQ. For KQs 1 and 2, we synthesized the evidence by clinical condition and type of intervention. For KQs 3, 4, and 5, we synthesized the evidence for all studies relevant to KQs 1 and 2. Detailed descriptions of included studies, key points, detailed synthesis, summary tables, and expanded strength-of-evidence tables that include the magnitude of effect can be found in the full report. Our summary of results, below, presents the strength-of-evidence grades.
Results of Literature Searches
Figure B presents our literature search results. Literature searches through December 8, 2011, for the current report identified 3,855 unduplicated citations. Hand searches of systematic reviews and other sources added a total of 124 citations. All these sources produced a total of 3,979 references.
After applying our eligibility and exclusion criteria to titles and abstracts of all identified citations, we obtained full-text copies of 729 published articles. We reapplied our inclusion criteria and excluded 661 articles.
The 68 articles included in this review for all KQs represent 62 studies. The full report provides appendixes that detail reasons for exclusion at the full-text stage, evidence tables, risk-of-bias assessments, a list of scales and measures, and detailed strength-of-evidence tables. Of the 68 included articles, 64 were randomized controlled trials (RCTs) and 4 were observational studies. Among the trials, 51 used a parallel randomization scheme, 12 used cluster randomization, and 1 used stratified randomization. Among the observational studies, 2 used a before-after design, 1 used an interrupted time series design with a concurrent control group, and 1 used a retrospective quasi-experimental design. We assessed 57 included articles as having medium risk of bias and 11 as having low risk of bias.
Figure B. Disposition of articles (PRISMA figure)
Abbreviations: NA = not applicable; PICOTS = populations, interventions, comparators, outcomes, timing, and settings; PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses; SR = systematic review.
Key Findings and Strength of Evidence
KQ 1: Effect of Patient, Provider, or Systems Interventions on Medication Adherence and Other Outcomes
Overall, the evidence from 57 trials in 63 articles included in this comparative effectiveness review suggests that numerous pathways provide opportunities to improve medication adherence across clinical conditions. These approaches include relatively low-cost, low-intensity telephone and mail interventions. They also include some relatively intense interventions, such as care coordination and case management (requiring close and ongoing monitoring of patients) and collaborative care; such interventions often require some, or even a good deal of, restructuring of typical approaches to health care delivery in the United States.
Despite such evidence about promising approaches to improving medication adherence, only a subset of these effective interventions relates better adherence with better health outcomes or other important end results. We found relatively little evidence linking improved adherence to improvements in other outcomes, such as biomarkers, morbidity, mortality, quality of life, quality of care, patient satisfaction, health care utilization, and costs.
Findings Specific to Clinical Conditions
The volume of evidence regarding improving medication adherence differs sharply by clinical condition. We found the greatest amount of evidence, in terms of numbers of trials or studies, numbers of subjects, or both, for hypertension and depression, followed by hyperlipidemia, asthma, and diabetes. The clinical conditions for which results are summarized in Table B are diabetes,33-37 hyperlipidemia,35, 38-46 hypertension,35,36,43,46-61 heart failure,62-65 myocardial infarction,66 asthma/chronic obstructive pulmonary disease,67-74 depression,33,48,75-86 glaucoma,87 multiple sclerosis,88 musculoskeletal diseases,89-91 and multiple or unspecified conditions.92-95 We did not find a substantial body of evidence testing varied approaches for several other clinical conditions. For musculoskeletal diseases, we found three trials that used interventions with no common features. Myocardial infarction, glaucoma, and multiple sclerosis had just one trial each. We found no eligible studies for cancer; likely reasons include the restrictions specified for this review to patient-administered medications and to outpatient settings. We found no eligible studies that explicitly focused on patients with adherence problems related to polypharmacy, although a few studies included patients with two or more conditions and assessed adherence to more than one medication.
Collectively, the most consistent evidence was that various types of interventions improved medication adherence outcomes for hypertension, heart failure, depression, and asthma. These improvements were accompanied by improvements in systolic and diastolic blood pressure for case management and face-to-face education with pharmacists for hypertension; reduced emergency department visits and improved patient satisfaction for pharmacist-led multicomponent interventions for heart failure; improved symptoms, pulmonary function, health care utilization, and quality of life for shared decisionmaking for asthma patients; improved symptoms for case management for depression; and improved symptoms and patient satisfaction with medications and quality of care for collaborative care for depression
We generally graded these interventions as beneficial with low to moderate strength of evidence, depending on the specific type of intervention. Of note, three clinical conditions (hypertension, heart failure, and depression) included some interventions for which evidence was insufficient due to lack of consistency or precision in the evidence (Table C).
For asthma and hypertension, because of several studies of low or moderate risk of bias that failed to find an effect, we judged that two interventions provided evidence of no benefit: these two interventions included collaborative care for hypertension and patient or provider access to patient adherence data for asthma.
Trials in diabetes, hyperlipidemia, and musculoskeletal diseases found a single intervention indicating benefit for medication adherence. These trials focused on care coordination and collaborative care approaches for diabetes, education and behavioral support for hyperlipidemia, and a virtual clinic for osteoporosis. All other approaches failed to produce improvements and were judged to be insufficient for lack of consistency or lack of precision in the results.
The least consistent evidence of improvement in medication adherence pertained to patients with multiple chronic conditions: three trials, using pharmacist-based outreach, education, and problem-solving approaches, provided evidence of no benefit for medication adherence, and findings from another trial, using case management, were insufficient.
We found the least evidence for myocardial infarction, glaucoma, and multiple sclerosis. Single trials in each of these clinical areas suggested low strength of evidence of benefit for medication adherence.
Findings Specific to Interventions
We identified 20 intervention approaches (Table C) across the clinical conditions included in this comparative effectiveness review. Intervention approaches tested in patient populations with different clinical conditions (either single diagnoses of chronic illnesses or, in some cases, two or more such ailments) included case management, collaborative care, decision aids, education, reminders, and pharmacist-led multicomponent approaches. Our findings suggest that educational interventions and case management approaches offer the most consistent and voluminous evidence of improvements in medication adherence across varied clinical conditions. We found moderate strength of evidence for self-management interventions for asthma, which generally include strong educational components. Trials showing improvement with case management and educational interventions provided some evidence of improvement for other health outcomes. We found low strength of evidence of benefit from educational interventions for medication adherence for hypertension, hyperlipidemia, and myocardial infarction, and insufficient evidence for diabetes. We found low or moderate strength of evidence of benefit from case management for diabetes, hypertension, heart failure, and depression; insufficient evidence for musculoskeletal diseases; and low strength of evidence of no benefit for persistence for multiple chronic conditions.
|Clinical Condition
|Type of Intervention
|Strength of Evidence for Medication Adherence
|Number of Studies; n of Individuals (n Analyzed); Results
|Strength of Evidence for Other Outcomes
|Number of Studies; n of Individuals (n Analyzed); Results
|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.
|Case management/ collaborative care33-35
|Low SOE of benefit for medication adherence
|3; 507 (507)
Varied measures and magnitude
|Low SOE of benefit for HbA1C
|1; 58 (58)
1.2 percentage points difference
|Education with social support36
|Insufficient for medication adherence
|1; 199 (189)
No stat sig difference
|Health coaching37
|Insufficient for medication adherence
|1; 56 (49)
No stat sig difference
|Collaborative care35
|Insufficient for medication adherence
|1; 329 (117 on lipid-lowering meds)
No stat sig difference
|Decision aids38-40
|Insufficient for medication adherence
|2; 248 (98 + NR in 1 trial)
Variable self-report measures with variable outcomes
|Low SOE of benefit for patient satisfaction
|1; 98 (98)
Variable self-report measures, some improvements for intervention group in specific areas
|Education and behavioral support (telephone or mail)41-45
|Low SOE of benefit for medication adherence
|5; 18,492 (9,411 + NR in 1 trial)
Variable measures (self-report, pharmacy refill) with variable outcomes
|Multicomponent (education face-to-face with pharmacist + blister packaging)46
|Insufficient for medication adherence
|1; 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-C
|1; 159 (135)
No stat sig difference between groups
|Blister packaging47
|Low SOE of benefit for medication adherence and persistence
|1; 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 stroke
|1; 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 + hospitalizations
|1; 93 (85)
No stat sig difference between groups for either outcome
|Case management48-50
|Low SOE of benefit for medication adherence
|3; 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 + DBP
|2; 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 care35,51,52
|Low SOE of no benefit for medication adherence
|3; 1,194 (785)
No stat sig differences between groups
|Education (face-to-face with pharmacist)46,53-55
|Low SOE of benefit for medication adherence; insufficient for persistence
|3; 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 SBP
|2; 292 (268)
-6.4 or -8.9 mm Hg mean SBP difference
|2; 292 (268)
1.1 or -4.4 mm Hg mean DBP difference
|Insufficient for quality of life
No stat sig differences for sexual dysfunction, dizziness, and headaches
|Low SOE of benefit for patient satisfaction
|1; 133 (130)
Stat sig improvement in 4 of 5 questions
|Low SOE of benefit for hospital visits
|1; 133 (124)
0.08 fewer hospital visits in intervention group
|Low SOE of benefit for contact withother health care providers
|1; 133 (124)
0.41 fewer visits in intervention group
|Insufficient for ED visits
|1; 133 (124)
No stat sig difference
|Education and behavioral support (telephone, mail, and/or video)43,56-60
|Low SOE of benefit for medication adherence
|5; 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 DBP
|1; 299 (267)
No stat sig difference between groups in change from baseline to 6 months
|Education with social support36
|Insufficient for medication adherence
|1; 199 (199)
No stat sig differences between groups at 12 months
|Risk communication61
|Insufficient for medication adherence
|1; 89 (89)
No stat sig difference between groups at 3 months
|Heart Failure
|Patient access to medical records62
|Insufficient for medication adherence
No stat sig difference at 6 or 12 months
|Case management63
|Low SOE of benefit for medication adherence
|1; 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 admission
|1; 156 (156)
No significant difference in multiple measures of all-cause readmission
|Multicomponent pharmacist led64
|Low SOE of benefit for medication adherence
|1; 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 life
No stat sig difference
|Low SOE of benefit for patient satisfaction
Difference of 0.3 on 12-point validated questionnaire
|Low SOE of benefit for all-cause ED visits and all-cause ED + hosp
|1; 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, costs
|1; 314 (314)
No stat sig difference
|Reminder video and telephone calls65
|Low SOE of benefit for medication adherence
|1; 60 (50)
Difference of 17% to 27% comparing video and telephone to control in MEMS adherence over 8 weeks
|Insufficient for quality of life
|1; 60 (42)
No stat sig difference
|Myocardial Infarction
|Education and behavioral support66
|Low SOE of benefit for medication adherence; insufficient for persistence
|1; 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
|Moderate SOE of short-term benefit in medication adherence
|Difference in percentage points for adherence: 14 to 31
|Insufficient for pulmonary function and inflammation markers
|2; 152 (149)
No stat sig difference
|Insufficient for symptom improvement
|5; 303 (300)
Varied measures and magnitude (inconsistent)
|Low SOE of no benefit for quality of life
|4; 248 (245)
Varied measures and magnitude (consistent)
|Shared or clinical decisionmaking72
|Low SOE of benefit for medication adherence
|1; 612 (612)
Difference in medication acquisition ratio for all asthma medications: 0.13 to 0.21
|Low SOE of benefit for pulmonary function
|1; 612 (612)
Difference in FEV1 percentage points: 2.7 to 3.4
|Low SOE of benefit for symptom improvement
|1; 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 life
|1; 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 utilization
|1; 612 (612)
Difference of 0.3 to 0.4 fewer asthma-related visits per year
|Asthma or COPD
|Pharmacist or physician access to patient adherence information73,74
|Low SOE of no benefit for medication adherence
|2; 3,811 (3,596)
No stat sig difference
|Case management33,48,75-77
|Moderate SOE of benefit for medication adherence
|3; 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 improvement
|3; 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 disability
|1; 386 (315)
Varied measures, outcomes, time periods
|Collaborative care78-83
|Moderate SOE of benefit for medication adherence for telephone + in person; insufficient for telephone only; insufficient for depression + HIV patients
|3 (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 depression
|Severe 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 antidepressants
|2; 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 utilization
|3; 598 (598)
Varied outcomes, time periods, and consistency
|Insufficient for costs
|1; 228 (228)
No stat sig difference
|Moderate SOE of benefit for patient satisfaction with quality of care
|3; 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 care84,85
|Insufficient for medication adherence
|2; 270 (255)
No stat sig difference
|Reminders to nonadherent patients and lists of nonadherent patients to providers86
|Low SOE of benefit for medication adherence
|1; 9,564 (9,564)
Difference in percentage points for adherence: 1 to 3 (range across study)
|Multicomponent intervention87
|Low SOE of benefit for medication adherence
|1; 66 (66)
Difference in adherence rate: 0.22
|Insufficient for intraocular pressure
|1; 66 (66)
No stat sig difference
|Multiple Sclerosis
|Counseling (software-based telephone)88
|Low SOE of benefit for medication adherence
|1; 435 (367)
Difference in percentage points of patients who discontinued use of multiple sclerosis therapy: 7.5
|Musculoskeletal Diseases
|Decision aid89
|Insufficient for medication adherence, persistence, initiation of therapy
|1; 100 (100)
Varied outcomes and measures
|Insufficient for patient satisfaction
No stat sig difference
|Case management90
|Insufficient for medication adherence
|1; 127 (127)
No stat sig difference
|Virtual osteoporosis clinic91
|Low SOE of benefit for medication adherence
|1; 235 (211)
Difference in percentage points of women using osteoporosis medication at 13 months: 23.7
|Insufficient for patient satisfaction
|1; 235 (211)
No stat sig difference
|Multiple or Unspecified Chronic Conditions
|Case management intervention92-94
|Low SOE of no benefit for persistence
|3; 3,307 (3,269)
No stat sig difference
|Outreach, education, and problem-solving (pharmacist led)95
|Insufficient for medication adherence
|1; 96 (75)
No stat sig difference
|Type of Intervention
|Heart Failure
|Myocardial Infarction
|Musculoskeletal Diseases
|Multiple or Unspecified Conditions
|Abbreviations: init = initiation of therapy; INS = insufficient; L(-) = low strength of evidence of no benefit; L(+) = low strength of evidence of benefit; M(+) = moderate strength of evidence of benefit; MA = medication adherence; MS = multiple sclerosis; pers = persistence.
|Blister packaging
Pers: L(+)
|Case management
|Pers: L(-)
|Collaborative care (telephone + in person)
|Collaborative care (telephone only)
|Counseling (software-based telephone)
|Decision aids
|MA, pers, init: INS
|Education (face-to-face with pharmacist)
Pers: INS
|Education + behavioral support (telephone, mail, and/or video)
Pers: INS
|Education + social support
|Health coaching
|Multicomponent interventions
|Outreach, education, and problem-solving
|Patient access to medical records
|Pharmacist or physician access to patient adherence data
|Risk communication
|Shared or clinical decisionmaking
|Virtual clinic
Other promising approaches tested and found to be effective in more than one clinical area include reminders and pharmacist-led multicomponent approaches. Interventions such as shared decisionmaking and blister packaging were tested in a single clinical area with a single trial; without additional evidence, their widespread applicability is difficult to judge but may well hold promise. Some interventions may be most effective for a particular clinical condition. Collaborative care appeared to be effective primarily for patients with depression or with depression and diabetes; for other clinical conditions (hyperlipidemia and hypertension), the evidence was insufficient.
The categories noted above are shorthand for one or more key elements of very diverse interventions. As explained earlier, we opted not to try to impose any external taxonomy on these markedly different programs; none seemed suitable for capturing the underlying constructs or specific activities we encountered in this literature. For instance, of the two trials categorized as interventions that gave health care providers access to patient adherence data, one included a substantial pharmaceutical care program, whereas the other did not. Thus, the inductive approach we used to identify types of interventions allowed us to group them in ways that seemed to reflect key similarities, but doing so limited our ability to draw firm conclusions about the effectiveness of specific intervention features. In addition, the trials that tested multicomponent efforts did not have multiple intervention arms that would have provided information about individual elements of the intervention effort. Nevertheless, we attempted to address this limitation through analyses for KQ 3, and those findings offer further insights on some common elements across these interventions.
KQ 2: Effect of Policy Interventions on Medication Adherence and Other Outcomes
Five studies96-100 evaluated the effects of policy-level interventions on medication adherence, specifically for cardiovascular disease, diabetes, and respiratory conditions (Table D). One study was an RCT. The other four studies used cohort designs. All of the studies assessed medication adherence using insurance claims data to measure either the medication possession ratio (MPR) or proportion of days covered (PDC). The use of similar adherence measures across the studies facilitates comparison of results.
All five studies evaluated policy-level interventions that reduced patient out-of-pocket expenses for prescription medications, either through reduced medication copayments or improved prescription drug coverage. The study by Zhang and colleagues evaluated the impact of Medicare Part D on medication adherence among groups of older adults who had different levels of prescription drug coverage prior to implementation of Medicare Part D.96 This study found a large improvement in adherence among individuals who had had no prescription drug coverage before Medicare Part D and smaller improvements among individuals with some prior coverage but whose out-of-pocket expenses were reduced following Medicare Part D implementation.
All five policy-level studies found statistically significant between-group differences in adherence to medications used to treat cardiovascular conditions favoring the group that had out-of-pocket expenses reduced. However, we find these differences somewhat difficult to interpret because medication adherence decreased over time in all groups in two of the studies that used cohort designs. Nonetheless, the magnitude of effects observed in the cohort studies were similar to those reported in the RCT.97 Therefore, we concluded that evidence of moderate strength indicates that policy-level interventions that reduce patient out-of-pocket expenses can have a beneficial effect on adherence to medications used to treat cardiovascular conditions.
Three policy-level studies found statistically significant between-group differences in adherence to medications used to treat diabetes favoring the group that had out-of-pocket expenses reduced. As above, we find these differences somewhat difficult to interpret because all of these studies used cohort designs and medication adherence decreased over time in all groups in two of the studies. Nonetheless, the magnitude of effects observed in these two studies were similar to those in the Medicare Part D study among individuals who had had some prescription drug coverage before Medicare Part D but whose out-of-pocket medication expenses following its implementation dropped.96 Therefore, we concluded that evidence of moderate strength indicates that policy-level interventions that reduce patient out-of-pocket expenses can have a beneficial effect on adherence to medications used to treat diabetes.
|Clinical Condition
|Number of Studies
|Medication Adherence
|Other Outcomes
aIncludes all policy-level interventions that reduced patient out-of-pocket expenses for prescription drugs.
|Cardiovascular disease96-100
|Improved prescription drug coveragea
|Unchanged prescription drug coverage
|Benefit: moderate SOE
|Insufficient SOE
|Improved prescription drug coverage a
|Unchanged prescription drug coverage
|Benefit: moderate SOE
|No evidence
|Inhaled corticosteroidsb,98
|Reduced medication copay
|Unchanged medication copay
|Insufficient SOE
|No evidence
One study found no effect of a policy-level intervention on adherence to inhaled corticosteroids, usually used to treat reactive airway disease conditions. Therefore, we concluded that evidence is insufficient to draw conclusions for the effectiveness of policy-level interventions in this clinical area.
One study examined the effect of policy-level interventions on clinical outcomes.97 This study found a 14-percent reduction in the rate of first vascular events following hospital discharge for a myocardial infarction. The same study found a 26-percent reduction in total patient spending but no change in total insurer paying. We concluded that evidence is insufficient to draw conclusions regarding the effects of policy-level interventions on clinical and economic outcomes.
KQ 3a: Characteristics of Medication Adherence
Overall, the extreme heterogeneity of terminology used to describe medication adherence interventions in the studies reviewed hindered our ability to compare effects of different features of the interventions across studies and across diseases. The diversity of the interventions themselves made identification of "intervention type" clusters challenging.
Most, but not all, studies provided information, although not in any standardized manner, about six key intervention characteristics: the target(s), the agent(s), and the mode(s) of the intervention, as well as their intensity, duration, and components. The characteristics provided a framework by which we could describe the interventions. For example, for the intervention target, a little more than 50 percent of the interventions aimed at various combinations of multiple targets, whereas nearly 40 percent targeted only patients. Similarly, for the agent of intervention delivery, a pharmacist, physician, or nurse delivered about half of interventions. About half of interventions involved at least some face-to-face delivery of the program.
In addition to characterizing the interventions for each of these six key features, we identified some general patterns of combinations of the six features. For example, interventions varied in the number of contacts they entailed from 1 to 30, but those with more contacts tended to involve telephone contact. Similarly, certain intervention components, such as facilitation and knowledge-based components affecting the delivery of medical information, were commonly used across most interventions. In contrast, others, such as motivational interviewing and contingent rewards, were used less commonly. Similarly, we noted a greater frequency of combining awareness-raising activities with knowledge delivery among nurse-delivered programs than among either pharmacist- or physician-delivered interventions. The specific components of the interventions were the least well-characterized aspect of this literature, although it was often these components that most meaningfully distinguished the interventions from one another. Some intervention types, such as decision aids, were not captured by existing taxonomies of adherence intervention components.
KQ 3b: Direct Comparisons of Medication Adherence Intervention Components
The vast majority of studies compared a multicomponent intervention to a usual-care control arm. Very few studies directly compared one feature of an intervention with another feature to determine which aspects of the intervention had the most effect on outcomes. A longstanding debate exists about the advantages and disadvantages of testing multicomponent interventions, which may increase the likelihood of having an impact, versus those of testing each component in isolation to understand its individual effects. Researchers may first combine approaches to document an effect and in later studies "peel away the layers of the onion" to isolate relative effects of separate components. The paucity of this second type of study design may reflect the state of the field. As studies increasingly demonstrate efficacious combination interventions, in the future we may see more studies that attempt to isolate effects of intervention features. Among the four studies that did conduct this kind of comparison, each compared different aspects of different interventions.
As a result, we could not pool data across even these four studies. One demonstrated that shared decisionmaking (in which nonphysician clinicians and patients negotiated a treatment regimen that accommodated patient goals and preferences) had a greater effect on adherence to asthma medications than did a clinical decisionmaking approach (in which the physician prescribed the treatment without specifically eliciting patient goals or preferences). Both approaches were more efficacious than usual care. The effects of shared decisionmaking on adherence lasted up to 2 years, whereas those attributed to clinical decisionmaking had attenuated at that point. Another study, conducted among patients with heart failure, directly compared two different delivery modes of the same information (telephone vs. videophone). This study found no difference between the two delivery modes regarding improvement in adherence, but both were superior to usual care. Another study directly compared the agent of delivery (physician vs. research staff) using the same mode (face-to-face contact) to deliver a decision aid among patients with diabetes to try to help them decide whether to take statins to lower their risk of cardiovascular disease. Patients who were given the decision aid had better adherence than those receiving usual care, regardless of who delivered the aid.
We conclude that mode of delivery was an important feature only in certain settings. However, incorporation of patient preferences through shared decisionmaking about treatment seems more efficacious at improving and sustaining improvement in asthma medication adherence than traditional clinical decisionmaking that does not take into account patient preferences in selecting a recommended treatment. Shared decisionmaking appeared to improve pulmonary function tests when compared with clinical decisionmaking, but this approach did not improve quality of life or health care utilization; we rated this evidence as having low strength (Table E).
|Clinical Condition
cation Adher-
Care Utiliz-
|Abbreviations: SOE = strength of evidence.
|No evid-
benefit: low
benefit: low
|No evid-
|No evid-
|No evid-
|No evid-
|No evid-
|No evid-
chronic conditions50
|Nurse case management
with tele-
|Nurse case
with tele-
and low-
|No evid-
|Not applicable
|No evid-
|No evid-
KQ 4: Outcomes for Vulnerable Populations
We searched for evidence on a broad set of vulnerable populations. For certain vulnerable subgroups—specifically for patients with major depression, severe depression, or depression and coexisting hypertension; Black patients with depression and coexisting diabetes; and elderly patients with diabetes, hyperlipidemia, heart failure, or hypertension—we determined that interventions with a positive impact on medication adherence had only low strength of evidence. Evidence was insufficient about benefit to adherence of interventions dealing with patients who had depression with coexisting HIV, patients who had diabetes and depression (except for Black patients with diabetes and depression), patients with diabetes and hypertension, and patients from rural communities. The low number of studies and limited sample size of included studies curtailed our confidence in the strength of evidence. For some vulnerable subgroups, including low-income patients and populations with low health literacy, we did not find any evidence.
KQ 5: Adverse Effects
Our review of studies that examined adverse events or harms associated with interventions aimed at improving adherence did not find any indication that these interventions resulted in any unintended negative consequences for patients. However, we found only three relevant studies, and the level of heterogeneity among these studies in terms of the intervention and outcomes was so great that we determined that the evidence was insufficient to reach definitive conclusions.
Key Findings and Strength of Evidence
We found evidence of effective interventions to improve medication adherence for many chronic conditions. These analyses suggest that patients' adherence to chronic-disease medications can be improved through programs targeting patients, providers, health systems, or policy. They demonstrated that a broad range of approaches can work.
Adherence is typically the result of a combination of patient, provider, and policy factors. Indeed, most of the interventions we identified were multifactorial; over half were aimed at multiple targets and most had multiple components, including several with multiple delivery modes. In other words, no single "silver bullet" exists for medication adherence.
We found the strongest evidence for enhancing adherence with reduced copays across clinical conditions, self-management of asthma (for short-term outcomes), and collaborative care or case management for depression. Within clinical conditions, we found the strongest evidence for depression case management for depression symptom improvement and pharmacist-led hypertension approaches for systolic blood pressure improvement. We found consistent evidence or evidence from more than one clinical area supporting medication adherence interventions such as education, reminders, and pharmacist-led multicomponent interventions.
Clinicians and policymakers should keep in mind that we found very little evidence of any relationship between medication adherence and adverse events, although what we found suggests that improving adherence did not increase the incidence of adverse events. However, many of the conditions studied did not involve medications typically associated with very severe common side effects. This review is the first we are aware of that systematically reviewed information on adverse events. It thus provides information that should be confirmed in future studies and reviews.
The lack of studies evaluating potential mechanisms that link improved adherence with other health-related or health services outcomes somewhat constrains policymakers' and clinicians' options. We did not find evidence of studies among patients with chronic illnesses that tend to have more intermittent disease trajectories, such as certain types of arthritis, diverticulitis, and other gastrointestinal conditions. In particular, decisionmakers should exercise caution in trying to use any a la carte approach to implementing components of complex interventions to enhance patients' medication adherence. We do not think that sufficient information is yet available to guide choices among the considerable array of program components, especially to pick and choose only some parts of multicomponent approaches. Therefore, future studies must do a better job not only of clearly describing each component of their intervention but also of designing studies and conducting analyses that can identify which components are driving the effects of the intervention. Meanwhile, however, if studies have not been done in their specific clinical patient population, clinicians and health system administrators may want to give more thought to how they might be able to extrapolate existing results to their specific patient populations—that is, take apparently successful programs and apply them to groups with diagnoses and other characteristics similar to those in the successful program. For example, interventions similar to those that were successful at improving adherence to medication for hypertension and hyperlipidemia may help in other settings in which the illness is asymptomatic and medication is taken primarily to prevent long-term complications.
Poor medication adherence is known to result in large downstream health care costs. An important finding for policymakers contemplating changes in health policy is our assessment of moderate-strength evidence from five consistent studies that reducing patients' out-of-pocket costs or improving prescription drug coverage can improve their medication-taking behavior. Policies that enhance patient adherence by easing patient copayments or other patient-paid medication expenses may prove highly cost-effective. Cost-effectiveness studies that assess the long-term effects of such policies could be beneficial to policymakers.
The interventions analyzed in this review were not highly selective; rather, they ranged from relatively minimalist to complex and intense, although evidence often came from small studies. Neither were these studies limited to narrow or unrepresentative disorders or disease severity; rather, they reflected studies done across a substantial variety of chronic conditions affecting adults. Thus, in one sense the evidence from this review might be regarded as relatively applicable across numerous different options for health care providers to pursue for their adult patients with major chronic diseases or multiple chronic conditions. Our findings are not generalizable to children or young adolescents because of our inclusion criteria.
As noted, many of our findings came from single, often small or short-term, trials, some with important questions about risk of bias. Findings from this diversity of clinical conditions and interventions have not yet been replicated in trials in larger patient populations, in groups drawn from different settings and with different sociodemographic characteristics, or in investigations with longer observation and followup periods. These gaps in the evidence base constrain somewhat the applicability of our results.
Another limitation to the applicability of this evidence comes from the complexity of multicomponent interventions. Studies did not generally provide information on how researchers identified the separate active components in their interventions or how they had operationalized those components; generally, these complex programs lacked detailed instructions and users' manuals by which other groups might try to replicate the original research.
Finally, the degree to which these interventions require fidelity to protocol when being implemented in other settings or through different study designs (e.g., nonexperimental studies) is unclear. The need for fidelity to protocol or the allowable appropriate adjustments for other patient populations (e.g., different illnesses, different sociodemographic characteristics) are likely a matter of some debate. These questions place some limits on the wide applicability of the evidence reported here.
The constraints for population and setting we imposed on the systematic review limit the applicability of this review, as discussed above. We did not review the evidence on populations with HIV/AIDS, mania, bipolar disorder, or substance abuse. We excluded studies among patients with HIV/AIDS because existing comprehensive reviews of these interventions had been conducted recently. We also excluded studies of acute conditions, severe mental illness, and substance abuse to improve our ability to potentially pool findings, since adherence for short-term acute conditions and those involving addictions or cognitive limitations is different from adherence for chronic medications. However, interventions for these excluded clinical conditions may have applicability to the conditions that we included in our review. We limited this review to adults and cannot, therefore, address important adherence concerns for children and adolescents with chronic conditions such as type 2 diabetes. Another limitation is geographic location: we excluded non-English and non-U.S. studies. This criterion may well have decreased the pool of eligible studies we might have examined, but the applicability of those studies to the United States is unclear. Our approach to categorizing interventions for KQ 1 relied essentially on the short descriptions in published manuscripts; their similarities or differences were substituted for any overarching taxonomy, as none that we considered seemed to fit our purpose. Thus, we have introduced intervention labels that, admittedly, do not fully describe or account for heterogeneity within and across clinical conditions or patient populations. This approach limits our ability to make definitive statements about the effectiveness of interventions across clinical areas; we believe the clusters and categorizations we used are useful heuristics, but they may be regarded more as hypothesis generating than as reflecting settled principles of classification. Our pool of included interventions is limited to those that were designed specifically to address medication adherence as a primary or secondary outcome. Finally, we did not include clinical trials of drugs that considered adherence as a component of safety and efficacy; as a result, we do not address the effectiveness of specific drug formulations that may improve adherence by limiting adverse effects.
Research Gaps
Our review identified several gaps in the literature that may be filled by future research efforts. In many disease areas for KQ 1, interventions and adherence measures were heterogeneous, which limited our ability to pool results from studies. If investigators could use more standardized objective adherence outcomes in future research, their results might be more easily analyzed and interpreted in the context of other adherence studies.
In addition, a lack of focus on mediating relationships through which the interventions acted on medication adherence limited the conclusions that we could safely draw about the efficacy of specific intervention features. Although some studies showed that interventions improved adherence, only a few had large effects on adherence. Hence, future studies could be designed to identify how to enhance the effects of efficacious interventions, such as by using a factorial design that combines efficacious interventions and can assess both additive and multiplicative effects.
Most trials were not placed in a larger context of improving the quality of health care delivered; only a minority examined issues such as quality of life and patient-reported outcomes or patient satisfaction. This limitation interacts with the issues noted above about understanding the effectiveness of these programs, not simply their efficacy, which is especially important for providing information suitable for broadly based clinical and policy decisionmaking. At a minimum, using guidelines from the Standards for Quality Improvement Reporting Excellence (SQUIRE) group (http://squire-statement.org/guidelines ) will improve the quality of reporting so that future studies of complex interventions routinely clarify the mechanisms by which intervention components are expected to cause change, the course of the implementation, and the success of tests of the mechanism of action.101
Finally, although many studies assessed some health outcomes, these often were not reported by patients themselves, and many were relatively short term (at least in the context of lifelong chronic ailments). Including long-term health outcomes and mounting efforts to solicit information directly from patients in future trials or observational studies of adherence would enhance the Nation's capacity to assess the overall significance of adherence interventions. While the minimum length of followup indicated may vary by condition, for lifelong chronic ailments, medication adherence often decays over at least the first year. Hence, studies that follow patients longer than 1 year could provide information about adherence levels once they have reached a plateau. Collecting information about costs will be crucial, because no health systems or facilities can afford to try all approaches across the diverse patient populations they serve. Economic information is essential in and of itself, but it will also facilitate cost-effectiveness analyses of such interventions.
Despite the heterogeneity of adherence measurement, interventions tested, and characterization of interventions, we found the most consistent evidence of improvement in medication adherence for policy-level interventions to reduce out-of-pocket expenses, case management, and educational interventions across clinical conditions. Within clinical conditions, we found the strongest support for self-management of medications for short-term improvement in adherence for asthma patients; collaborative care or case management programs for short-term improvement of adherence and symptom improvement for patients taking depression medications; and pharmacist-led approaches for hypertensive patients to improve systolic blood pressure.
We found low strength of evidence for many other interventions; these diverse groups of approaches offer promise but require more research to establish their value (or lack of it). Far less evidence was available to show whether most of these interventions improved patients' health outcomes, given better adherence to their medication regimens. Several reviews that researchers have conducted over the past two decades—now complemented by our review—confirm that medication adherence can be improved via formal programs of various sorts. At this stage, new studies need to be asking, "What specific intervention element or elements work best for improving medication adherence?" and "How can we further enhance medication adherence interventions to improve health outcomes?"
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- Berg J, Dunbar-Jacob J, Sereika SM. An evaluation of a self-management program for adults with asthma. Clin Nurs Res. 1997 Aug;6(3):225-38. PMID: 9281927.
- Janson SL, Fahy JV, Covington JK, et al. Effects of individual self-management education on clinical, biological, and adherence outcomes in asthma. Am J Med. 2003 Dec 1;115(8):620-6. PMID: 14656614.
- Janson SL, McGrath KW, Covington JK, et al. Individualized asthma self-management improves medication adherence and markers of asthma control. J Allergy Clin Immunol. 2009 Apr;123(4):840-6. PMID: 19348923.
- Schaffer SD, Tian L. Promoting adherence: effects of theory-based asthma education. Clin Nurs Res. 2004 Feb;13(1):69-89. PMID: 14768768.
- Wilson SR, Strub P, Buist AS, et al. Shared treatment decision making improves adherence and outcomes in poorly controlled asthma. Am J Respir Crit Care Med. 2010 Mar 15;181(6):566-77. PMID: 20019345.
- Weinberger M, Murray MD, Marrero DG, et al. Effectiveness of pharmacist care for patients with reactive airways disease: a randomized controlled trial. JAMA. 2002 Oct 2;288(13):1594-602. PMID: 12350190.
- Williams LK, Peterson EL, Wells K, et al. A cluster-randomized trial to provide clinicians inhaled corticosteroid adherence information for their patients with asthma. J Allergy Clin Immunol. 2010 Aug;126(2):225-31, 231.e1-4. PMID: 20569973.
- Katon W, Rutter C, Ludman EJ, et al. A randomized trial of relapse prevention of depression in primary care. Arch Gen Psychiatry. 2001 Mar;58(3):241-7. PMID: 11231831.
- Ludman E, Katon W, Bush T, et al. Behavioural factors associated with symptom outcomes in a primary care-based depression prevention intervention trial. Psychol Med. 2003 Aug;33(6):1061-70. PMID: 12946090.
- Von Korff M, Katon W, Rutter C, et al. Effect on disability outcomes of a depression relapse prevention program. Psychosom Med. 2003 Nov-Dec;65(6):938-43. PMID: 14645770.
- Capoccia KL, Boudreau DM, Blough DK, et al. Randomized trial of pharmacist interventions to improve depression care and outcomes in primary care. Am J Health Syst Pharm. 2004 Feb 15;61(4):364-72. PMID: 15011764.
- Katon W, Von Korff M, Lin E, et al. Collaborative management to achieve treatment guidelines. Impact on depression in primary care. JAMA. 1995 Apr 5;273(13):1026-31. PMID: 7897786.
- Katon W, Robinson P, Von Korff M, et al. A multifaceted intervention to improve treatment of depression in primary care. Arch Gen Psychiatry. 1996 Oct;53(10):924-32. PMID: 8857869.
- Katon W, Von Korff M, Lin E, et al. Stepped collaborative care for primary care patients with persistent symptoms of depression: a randomized trial. Arch Gen Psychiatry. 1999;56(12):1109-15.
- Katon W, Russo J, Von Korff M, et al. Long-term effects of a collaborative care intervention in persistently depressed primary care patients. J Gen Intern Med. 2002 Oct;17(10):741-8. PMID: 12390549.
- Pyne JM, Fortney JC, Curran GM, et al. Effectiveness of collaborative care for depression in human immunodeficiency virus clinics. Arch Intern Med. 2011 Jan 10;171(1):23-31. PMID: 21220657.
- Rickles NM, Svarstad BL, Statz-Paynter JL, et al. Pharmacist telemonitoring of antidepressant use: effects on pharmacist-patient collaboration. J Am Pharm Assoc (2003). 2005 May-Jun;45(3):344-53. PMID: 15991756.
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- Okeke CO, Quigley HA, Jampel HD, et al. Interventions improve poor adherence with once daily glaucoma medications in electronically monitored patients. Ophthalmology. 2009 Dec;116(12):2286-93. PMID: 19815286.
- Berger BA, Liang H, Hudmon KS. Evaluation of software-based telephone counseling to enhance medication persistency among patients with multiple sclerosis. J Am Pharm Assoc (2003). 2005 Jul-Aug;45(4):466-72. PMID: 16128502.
- Montori VM, Shah ND, Pencille LJ, et al. Use of a decision aid to improve treatment decisions in osteoporosis: the osteoporosis choice randomized trial. Am J Med. 2011 Jun;124(6):549-56. PMID: 21605732.
- Rudd RE, Blanch DC, Gall V, et al. A randomized controlled trial of an intervention to reduce low literacy barriers in inflammatory arthritis management. Patient Educ Couns. 2009 Jun;75(3):334-9. PMID: 19345053.
- Waalen J, Bruning AL, Peters MJ, et al. A telephone-based intervention for increasing the use of osteoporosis medication: a randomized controlled trial. Am J Manag Care. 2009 Aug;15(8):e60-70. PMID: 19659407.
- Nietert PJ, Tilley BC, Zhao W, et al. Two pharmacy interventions to improve refill persistence for chronic disease medications: a randomized, controlled trial. Med Care. 2009 Jan;47(1):32-40. PMID: 19106728.
- Schnipper JL, Kirwin JL, Cotugno MC, et al. Role of pharmacist counseling in preventing adverse drug events after hospitalization. Arch Intern Med. 2006 Mar 13;166(5):565-71. PMID: 16534045.
- Taylor CT, Byrd DC, Krueger K. Improving primary care in rural Alabama with a pharmacy initiative. Am J Health Syst Pharm. 2003 Jun 1;60(11):1123-9. PMID: 12816022.
- Sledge WH, Brown KE, Levine JM, et al. A randomized trial of primary intensive care to reduce hospital admissions in patients with high utilization of inpatient services. Dis Manag. 2006 Dec;9(6):328-38. PMID: 17115880.
- Zhang Y, Lave JR, Donohue JM, et al. The impact of Medicare Part D on medication adherence among older adults enrolled in Medicare-Advantage products. Med Care. 2010 May;48(5):409-17. PMID: 20393360.
- Choudhry NK, Avorn J, Glynn RJ, et al. Full coverage for preventive medications after myocardial infarction. N Engl J Med. 2011 Dec 1;365(22):2088-97. PMID: 22080794.
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- Choudhry NK, Fischer MA, Avorn J, et al. At Pitney Bowes, value-based insurance design cut copayments and increased drug adherence. Health Aff (Millwood). 2010 Nov;29(11):1995-2001. PMID: 21041738.
- Maciejewski ML, Farley JF, Parker J, et al. Copayment reductions generate greater medication adherence in targeted patients. Health Aff (Millwood). 2010 Nov;29(11):2002-8. PMID: 21041739.
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Full Report
This executive summary is part of the following document: Viswanathan M, Golin CE, Jones CD, Ashok M, Blalock S, Wines RCM, Coker-Schwimmer EJL, Grodensky CA, Rosen DL, Yuen A, Sista P, Lohr KN. Medication Adherence Interventions: Comparative Effectiveness. Closing the Quality Gap: Revisiting the State of the Science. Evidence Report No. 208. (Prepared by RTI International–University of North Carolina Evidence-based Practice Center under Contract No. 290-2007-10056-I.) AHRQ Publication No. 12-E010-EF. Rockville, MD: Agency for Healthcare Research and Quality. September 2012. www.effectivehealthcare.ahrq.gov/reports/final.cfm.
For More Copies
For more copies of Medication Adherence Interventions: Comparative Effectiveness. Closing the Quality Gap: Revisiting the State of the Science: Evidence Report No. 208 (AHRQ Publication No. 12-E010-1), please call the AHRQ Publications Clearinghouse at 800–358–9295 or email firstname.lastname@example.com.


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Retailers to reveal readiness for spending cuts
Monday 18 October 2010 - Editorial Assistant
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The Whale + Celtic Requiem
John Tavener's The Whale and Celtic Requiem are two of the most extraordinary records ever issued, certainly on Apple Records, and most likely on any mainstream label. A bold claim, perhaps. But listen first and then decide.
The 1960s are, of course, synonymous with all that was novel and innovative in society and culture, typified by an explosion of radical ideas ripping through film, literature, art and music. But by the end of the decade, this revolutionary mood had yet to permeate through to classical music, the final bastion of the establishment. Even contemporary music, that post-1945 school that by definition was rooted firmly in the now, was doing little that was different or challenging.
John Tavener's compositions of the period, particularly The Whale, changed all that. Written between 1965 and 1966, it was as if all the pent-up creativity, restrained by classical convention since the Second World War, was suddenly liberated through the agency of this one astonishing, ground-breaking work.
Despite his irregular approach, John Tavener was a product of the establishment, and was publicly educated at Highgate School, in north London, before graduating from the Royal Academy of Music. He looked to Bach and Mozart for his inspiration, as well as one of the 20th century's leading composers, Stravinksy.
Sir John Tavener remains a profoundly spiritual and religious man, initially focusing on Christianity via its various denominations, but more recently exploring many of the world's other theological traditions. He embraces religious subject matter as the lifeblood of his music. It was within this context that his maverick spirit broke free.
The Whale is a cantata, a medium-scale descriptive piece for chorus and orchestra. But it was unlike any cantata ever heard before. "Contemporary music at that time was in a cul-de-sac," says Sir John Tavener today. "I wanted to bring it to a wider audience. The Whale was in the category of so-called serious music, and yet it brings together a wide series of musical styles. It was influenced by people such as The Beatles, the spirit of the times, and I think The Whale certainly had a pop element to it."
"It was entirely different," confirms James Rushton, managing director of Chester Music, and John Tavener's long-standing music publisher. "The Whale uses techniques like serial writing, but it did it in the setting of a very immediate, in-your-face colourful story. It has pre-recorded electronics, a narrator and, at certain points jazz and pop influenced elements. It is very diverse in that way and totally at odds with what classical music expected of the contemporary composer at that stage."
The Whale tells the Old Testament story of the reluctant prophet Jonah, who disobeys God, flees on board a ship, only to be thrown overboard during a storm by the God-fearing crew. Jonah is swallowed by a whale, and is kept inside its belly for three days. Repentant, Jonah then does as instructed and travels to Nineveh to convert this errant city to the ways of the Lord.
The Whale is a riot of ideas. It revels in unconventional scoring and dynamic sound pictures in its recounting of the biblical story. It opens with BBC radio newsreader Alvar Lidell, one of the most distinctive broadcast voices of the 20th century, as the narrator, reading an encylopaedia entry on the sea mammal "of the order of cetacea".
The traditional orchestra and chorus are augmented by non-musical instruments such as a whip and a football rattle. "I love the percussive sounds they make", says Sir John. Five performers are required to shout through loud hailers; and there is an improvised section during 'In The Belly' (Track 7), which the score instructs the choir to: "clap hands, neigh, grunt, snort, yawn, make vomiting noises, whisper, cough, shuffle, hum and talk to each other — in any order".
In 2004, Sir John said: "The Whale is piece written by an angry young man. I was angry because the world didn't see the cosmos in metaphysical terms. I was also angry because what I saw of so-called classical music in those days was very po-faced. I wrote The Whale as a reaction in a way. The piece is very fantastical."
The Whale received rapturous accolades that instantly elevated John Tavener from a young composer at the beginning of his career into a fully-formed master at the very top of the contemporary music scene. In a review of a live performance in January 1968, The Observer concluded that it was "an enormous success, and a great victory for those who recognize that modern music is not simply a matter of solemn incantations in the sacred name of tedium."
Like The Whale, Celtic Requiem, which was written in 1969, is a religious commentary rather than a work that's overtly devotional, as much of John Tavener's later music would become. Its musical inspiration is J.S. Bach, quotes from whom are incorporated into Celtic Requiem and interact with Tavener's own.
"I love it," says Sir John today of Celtic Requiem. "I love the sound world of it. And I love the idea of it." The idea is one of contrasts, in which solemn phrases from the traditional Requiem Mass are juxtaposed against age-old Irish children's rhymes and games that deal with death in an unflinching, matter-of-fact way.
The piece hinges on the rhyme of 'Jenny Jones' that John discovered in a book by David Holbrook about traditional children's games — 'Jenny Jones is dead / Is dead / She is dead / She is dead // Jenny Jones is dead / Is dead / You can't see her now!'. "I think it's the most ancient of those children's songs," says Sir John.
Celtic Requiem is theatrical and evocative, and in parts, eerie. There's another outing for the whip, and with dinner gongs, Aeolian bagpipes, electric and bass guitar augmenting the orchestra, high soprano and children's choir, it is another daring, unusual work. Witness the immense, dark power of the organ in 'Requiescat In Pace' ('Rest In Peace' / Track 11), which the organist (Tavener himself) plays a 'full manual cluster' by slamming hands and forearms firmly over the entire length of the keyboard; and the nagging children's chant of 'Mary had a little lamb / Little lamb / Little lamb / Mary had a little lamb / Her father shot it in the head!'.
John Tavener remains delighted that Apple Records was supportive of his early works. "It was marvellously refreshing because serious music at that time was very humourless and narrow," he says today, "and if recorded at all, therefore tended to be on very obscure labels. To have Apple take on The Whale and Celtic Requiem was wonderful."
John had two sponsors at Apple, John Lennon and Ringo Starr. He recalls meeting John Lennon and Yoko Ono at a dinner party one night, where they swapped tapes and exchanged ideas. And Ringo? "I met Ringo at my brother's house," Sir John says. At that time, Roger Tavener ran the family's up-market building firm and was renovating Ringo's home in Highgate. Sir John adds: "My brother had prepared caviar, but Ringo just wanted a jam sandwich. We finally agreed to record The Whale at that meeting."
"Ringo came to all the rehearsals and the recordings of The Whale and Celtic Requiem," adds Sir John. Indeed, Ringo is one of those shouting through a loud hailer in 'Melodrama & Pantomime' on The Whale ("…and cause suffocation!" on Track 2, at 0:48). What do you think Ringo saw in your music? "I think it was the wildness. I was less surprised at John Lennon's enthusiasm, but I was surprised at Ringo's."
"John and Ringo were very important to me," Sir John admits. "They were lovely people. I don't think I could actually call them friends but they were wonderful people to meet."
Sir John has been closely involved with this remastered edition of The Whale and Celtic Requiem, first issued in 1970 and 1971 respectively. He has re-presented both works to match how they are shown in the scores. Instead of spanning two tracks as per all previous releases, The Whale has been split into its eight discrete sections. Celtic Requiem, meanwhile, is now presented in three parts, instead of its previous one. For the first time, listeners can now follow on CD the individual elements of these early and most original works.
Says Sir John of The Whale and Celtic Requiem today: "I have been listening to them recently and I find them wonderfully fresh. And enormously accomplished for the time that they were written. I feel very sympathetic towards them."
The two short supporting pieces on this CD, Nomine Jesu and Coplas, are key early works that John later fully realized into his next major composition, Ultimos Ritos (Spanish for 'Last Rites'), which was premiered in 1972.
Nomine Jesu is a multi-lingual, multi-cultural meditation on the name of Jesus, which proclaims: "Every tongue should confess that Jesus Christ is Lord to the glory of God The Father". Like Celtic Requiem, it is a 'static' work, based on one chord. Its chief inspiration is the writings of St. John of the Cross, a 16th century mystical poet of the Counter Reformation period, when what had once been heresy could again become sacred. The mystical idea of St. John of the Cross — 'the more I live the more I must die' — "obsesses me," Sir John has written.
Coplas, too, refers to the mystical poetry of St. John of the Cross, in which the bride is represented by the soul and the groom is represented by Jesus. A marriage, then, that is indeed made in heaven. "I love the sacred erotic element of the poetry of St. John's writings," says Sir John today. "The idea of God as lover. That was essential and very attractive to me."
Coplas is a piece of sublime serenity written for choir and tape. It is light of touch and heavy with symbolism. When performed, the choir assemble in a cruciform motif, the shape of the Christian cross (as it does for Ultimos Ritos). The work draws upon the closing chords of Bach's Mass In B Minor, a tape recording of which is set beneath a slow-motion melody of John Tavener's own. Over nine minutes, Tavener is slowly absorbed by Bach.
"Ultimos Ritos is about the mystical concept of 'dying to oneself'," wrote John Tavener in the work's original programme notes. "When Christ calls men, he bids them 'come and die'. I have tried to express this 'dying to oneself' by a simple musical idea."
John Tavener was knighted by the Queen in 2000 for his services to music. For him, music is not merely artistic expression. Instead, his belief in God and his desire to articulate his relationship with the divine is paramount. "God shows himself in everything that lives," he has said, "and this includes the sublime language of music."
"My life has taught me that music has a primordial origin," Sir John concludes today. "I can't really explain it. I wanted to produce music that was the sound of God. That's what I have always tried to do."
- Producer
- Michael Bremner
- Recorded at
- Church Of St. John The Evangelist, Islington, London
- The Whale Released (UK)
- 25/09/70
- The Whale Released (US)
- 09/11/70
- Celtic Requiem Released (UK)
- 02/07/71


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Being a first time dog owner I just received my pup back from the trainer this week and couldn't be happier with the progression the trainer has made with my pup. I think the most beneficial thing from his training was being able to use his own "fully" trained dogs to lead by example. Having a dog watch another dog do it the right way has to be one of the most better parts of training I'm sure of it. Another benefit would be the daily exposure to live birds. I live in the city and have no place to keep live birds, nor know what to do with them!
That's my boy "Blue"!!!! Flyin High in the Passenger Side x Katie May of Belgrade
I'm hoping there is a happy medium
I'm not riled up about anything. I just don't see what the issue is. Find yourself a well respected pro that takes good care of the dogs and knows how to get through to them. If you trust the pro your mind will be eased I'm sure. The most important thing you and the dog can gain from the use of a pro is more knowledge for you and the dog. They can be spoiled again when they get home. FWIW I would never buy a dog and just stick it on a pros truck for good. My dogs are pets and hunting buddies first, competitive dogs second. I def agree with the quality of life deal when a dog is sent off for extreme periods of time. I'm sure they could stand a visit or two to home.
It is a pro's job to train your dog, and the time s/he spends with your dog will be doing that. The rest of the day, for the dog, is spent being a dog-waiting to train, airing, eating, sleeping. You should not expect that your dog will be your pro's "pet" while the dog is there-that is not what you are hiring the pro to do. Dogs do just fine in that environment. They have structure, they know what to expect, they get to work lots, every day, which they love. They are not people. They do not miss you like you miss them when they are gone, but they will be happy to see you when they get back
Marlana Smith
APR SHR TDK's Dusty Gunslinger JH - "Churchill"
CPR Max's Black Diamond Girl Scout JH - "Scout"
An ounce of prevention is worth a pound of cure.
[QUOTE=EdA;1145502]There is a happy medium. Also professional dog trainers are no different than the rest of society, some are good trainers with poor people skills, some have good people skills but are not good trainers, and some are good trainers with good people skills. Find one that suits you and your needs.[/
I agree and the other thing you can do is find one close by that will let you be involved in the process. I had trained my own dogs before but learned a lot more about training when my dogs went to a pro.
Brent McDowell
"To be the best, you gotta beat the best - WOOOOOO!!!"
Jake's Pintail Hunter - Jake
HR April's Yellow Daisy JH - Daisy
Knob Creek's Rough Rider*** - Rex
Knob Creek's Straight Outta Compton - Cali


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When it comes to marketing, entrepreneurs have to remember that it isn't always an "either/or" proposition, especially with small business owners that already have a physical presence with brick-and-mortar stores in place. You can still pursue traditional offline marketing techniques while getting your brand's message out to a broader audience range through social media platforms. Diversity is key to capturing as much of your market as possible and offline marketing, for all intents and purposes, isn't dead just yet – it's still a tried and true method in the following areas.
Print Ads
Although newspapers may be seen as a dying medium with its main consumer base composed of baby boomers, there is a still good reason for you to have an ad printed in your local paper. According to the 2013 Nielsen National Cross-Media Engagement Study, newspapers have the highest advertising effectiveness ratings, beating social media, TV and radio in "Likely to Purchase," "Usually Noticed" and "Advertising Annoyance" categories.


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First of all, does anyone doubt that the WH wants to keep this issue before the public so we're not talking about the WH scandals? The IRS? The NSA? fast & Furious? Benghazi? etc.
Secondly, has there ever been a more narcissistic person in the WH? Everything ends up being about him.
When the left says we need to have a conversation about race what they mean is that people on the right need to sit down and shite up and listen to people on the left bitch. They do NOT mean that conservatives and/or whites get to air their grievances as well. It is always a very one-sided "conversation" that more closely resembles a lecture or a scolding. Witness what the left did to Bill Cosby when he criticized the black community.
Sure, and it's the kind of thing that pisses you off. But it doesn't stop you from going to school or getting a job, or raising a family in a 2-parent home, or staying off drugs, etc. It hurts your feelings, but it doesn't excuse or justify the rampant problems that exist in the black community today.
How can it when race pimps like Obama, Sharpton, Jackson, et al never shut up about it? And they'll never shut up about it as long as they keep making money off of it or getting re-elected because of it.
This is downright evil on Obama's part to engage in this type of senseless speculation. In other words, it's exactly what we don't need right now. But Obama never passes up an opportunity to make matters worse when it comes to matters of race.
Once again, senseless speculation that only feeds the flames of racial hatred.
Way to go, Odummy. In my mind you've gone from being a horrible president to being downright evil.
And those of us in authority should be doing everything we can to encourage the better angels of our nature, as opposed to using these episodes to heighten divisions.
Secondly, has there ever been a more narcissistic person in the WH? Everything ends up being about him.
Random thoughts on Obama's impromptu speech today
Could not be more hypocritical.
What was clear from start to finish is that Obama picked a "side" on this case... a case in which hard evidence was in extremely short supply, and he has no way of knowing whether he's chosen the right side or the wrong side (none of us truly do). His stance is wreckless when you consider the possibility that Zimmerman's life was unjustly threatened is at least (as trial and evidence (or lack thereof) supports) as likely as the fact that Trayvon's life was unjustly threatened.
It's just disturbing that the public consciousness isn't aware of how wreckless and divisive his stance and contributions to this situation are.
he has no way of knowing whether he's chosen the right side or the wrong side (none of us truly do).
It's going to take a lot to top him. LBJ comes close IMO.
Notice how he frames an alternative scenario in which Travon was white.
The DA didn't bring up race either
What is the new issue about race now? Total absurdity
She brought up profiling but didn't go into race specifically which was really weird?
We have 100 protest scheduled this weekend and Obama wants to show his black unity. They are mad about the outcome and its second nature to play the victim.
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