0
Reviews |

Interventions to Improve Adherence to Self-administered Medications for Chronic Diseases in the United States: A Systematic Review FREE

Meera Viswanathan, PhD; Carol E. Golin, MD; Christine D. Jones, MD, MS; Mahima Ashok, PhD; Susan J. Blalock, MPH, PhD; Roberta C.M. Wines, MPH; Emmanuel J.L. Coker-Schwimmer, MPH; David L. Rosen, MD, PhD; Priyanka Sista, BA; and Kathleen N. Lohr, PhD
[+] Article and Author Information

This article was published at www.annals.org on 11 September 2012.


From RTI International, Durham, and University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Note: RTI International is a trade name of Research Triangle Institute.

Disclaimer: The findings and conclusions in this article are those of the authors, who are responsible for its contents; they do not necessarily represent the view of AHRQ or the Veterans Health Administration. Therefore, no statement in this report should be construed as an official position of these entities, the U.S. Department of Health and Human Services, or the U.S. Department of Veterans Affairs.

Acknowledgment: The authors thank the Evidence-based Practice Center (EPC) team staff at RTI International and the University of North Carolina at Chapel Hill for their considerable support, commitment, and contributions; Timothy S. Carey, MD, MPH, Director of the Cecil G. Sheps Center for Health Services Research at the University of North Carolina; Christiane Voisin, MSLS, EPC Librarian; Audrey R. Holland, MPH, and Elizabeth Harden, MPH, EPC Project Managers; Catherine A. Grodensky, MPH, and Andrea Yuen, BS, abstractors; Laura Small, BA, EPC editor; and Loraine Monroe, EPC publications specialist.

Financial Support: By AHRQ (contract 290200710056I). Dr. Jones is supported by an NIH/HRSA training grant (T32HP14001-25).

Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M12-1030.

Requests for Single Reprints: Meera Viswanathan, PhD, Social, Statistical, and Environmental Sciences, RTI International, 3040 Cornwallis Road, Durham, NC 27709; e-mail, viswanathan@rti.org.

Current Author Addresses: Drs. Viswanathan and Lohr: Social, Statistical, and Environmental Sciences, RTI International, 3040 Cornwallis Road, Durham, NC 27709.

Dr. Golin, Ms. Wines, and Mr. Coker-Schwimmer: Cecil G. Sheps Center for Health Services Research, University of North Carolina, Chapel Hill, 725 Martin Luther King Jr. Boulevard, CB #7590, Chapel Hill, NC 27599-7590.

Dr. Jones: UNC General Medicine, 5034 Old Clinic Building, CB #7110, Chapel Hill, NC 27599-7110.

Dr. Ashok: Social, Statistical, and Environmental Sciences, RTI International, 1440 Main Street, Suite 310, Waltham, MA 02451.

Dr. Blalock: Eshelman School of Pharmacy, University of North Carolina, 2213 Kerr Hall, Chapel Hill, NC 27599-7573.

Dr. Rosen: University of North Carolina at Chapel Hill, 130 Mason Farm Road, CB #7215, Chapel Hill, NC 27599-7215.

Ms. Sista: UNC at Chapel Hill School of Medicine, 1001 Bondurant Hall, CB #9535, Chapel Hill, NC 27599-9535.

Author Contributions: Conception and design: M. Viswanathan, C.E. Golin, C.D. Jones, M. Ashok, S.J. Blalock.

Analysis and interpretation of the data: M. Viswanathan, C.E. Golin, C.D. Jones, M. Ashok, S.J. Blalock, E.J.L. Coker-Schwimmer, D.L. Rosen, K.N. Lohr.

Drafting of the article: M. Viswanathan, C.E. Golin, M. Ashok, S.J. Blalock, D.L. Rosen, K.N. Lohr.

Critical revision of the article for important intellectual content: M. Viswanathan, C.E. Golin, C.D. Jones, M. Ashok, S.J. Blalock, K.N. Lohr.

Final approval of the article: M. Viswanathan, C.E. Golin, C.D. Jones, M. Ashok, S.J. Blalock, D.L. Rosen, K.N. Lohr.

Statistical expertise: M. Viswanathan, D.L. Rosen.

Obtaining of funding: M. Viswanathan, C.E. Golin.

Administrative, technical, or logistic support: M. Viswanathan, C.E. Golin, R.C.M. Wines, E.J.L. Coker-Schwimmer, P. Sista, K.N. Lohr.

Collection and assembly of data: M. Viswanathan, C.E. Golin, C.D. Jones, M. Ashok, R.C.M. Wines, E.J.L. Coker-Schwimmer, D.L. Rosen, P. Sista.


Ann Intern Med. 2012;157(11):785-795. doi:10.7326/0003-4819-157-11-201212040-00538
Text Size: A A A

Background: Suboptimum medication adherence is common in the United States and leads to serious negative health consequences but may respond to intervention.

Purpose: To assess the comparative effectiveness of patient, provider, systems, and policy interventions that aim to improve medication adherence for chronic health conditions in the United States.

Data Sources: Eligible peer-reviewed publications from MEDLINE and the Cochrane Library indexed through 4 June 2012 and additional studies from reference lists and technical experts.

Study Selection: Randomized, controlled trials of patient, provider, or systems interventions to improve adherence to long-term medications and nonrandomized studies of policy interventions to improve medication adherence.

Data Extraction: Two investigators independently selected, extracted data from, and rated the risk of bias of relevant studies.

Data Synthesis: The evidence was synthesized separately for each clinical condition; within each condition, the type of intervention was synthesized. Two reviewers graded the strength of evidence by using established criteria. From 4124 eligible abstracts, 62 trials of patient-, provider-, or systems-level interventions evaluated 18 types of interventions; another 4 observational studies and 1 trial of policy interventions evaluated the effect of reduced medication copayments or improved prescription drug coverage. Clinical conditions amenable to multiple approaches to improving adherence include hypertension, heart failure, depression, and asthma. Interventions that improve adherence across multiple clinical conditions include policy interventions to reduce copayments or improve prescription drug coverage, systems interventions to offer case management, and patient-level educational interventions with behavioral support.

Limitations: Studies were limited to adults with chronic conditions (excluding HIV, AIDS, severe mental illness, and substance abuse) in the United States. Clinical and methodological heterogeneity hindered quantitative data pooling.

Conclusion: Reduced out-of-pocket expenses, case management, and patient education with behavioral support all improved medication adherence for more than 1 condition. Evidence is limited on whether these approaches are broadly applicable or affect long-term medication adherence and health outcomes.

Primary Funding Source: Agency for Healthcare Research and Quality.


Although many efficacious medical treatments exist, a recent Institute of Medicine report identified a gap between current treatment success rates and those believed to be achievable (1). This gap has been attributed partly to lack of patient adherence to recommended treatment (12). Poor medication adherence is common (34). Studies have consistently shown that 20% to 30% of medication prescriptions are never filled and that approximately 50% of medications for chronic disease are not taken as prescribed (56).

This lack of adherence has dramatic effects on health (5, 716). In the United States, it is estimated to cause approximately 125 000 deaths, at least 10% of hospitalizations (5), and a substantial increase in morbidity and mortality (1112). Nonadherence has been estimated to cost the U.S. health care system between $100 billion and $289 billion annually (3, 5, 1720).

This review is part of a larger initiative, Closing the Quality Gap: Revisiting the State of the Science, and builds on an earlier Agency for Healthcare Research and Quality (AHRQ) collection of publications, Closing the Quality Gap: A Critical Analysis of Quality Improvement Strategies (21). This new series focuses on selected settings, interventions, and clinical conditions for quality improvement. Our report addresses the comparative effectiveness of interventions to improve medication adherence.

The protocol and full review are available online at http://effectivehealthcare.ahrq.gov. This article focuses on 2 of our key questions. First, among patients with chronic diseases with self-administered medication prescribed by a provider for secondary or tertiary prevention, what is the comparative effectiveness of interventions aimed at patients, providers, or systems in improving medication adherence? Is improved medication adherence associated with improved patient outcomes? Second, what is the comparative effectiveness of policy interventions for improving medication adherence? Is improved medication adherence associated with improved patient outcomes?

Study Eligibility

We assessed medication adherence effectiveness for studies conducted in outpatient primary and specialty care, as well as community-based and home-based settings (Appendix Table 1). We excluded studies in institutional settings because medications are generally not self-administered there, interventions to improve antiretroviral adherence because comprehensive reviews of such interventions were only recently completed (2223), interventions for adherence to medications for patients with severe mental illness (schizophrenia, other psychoses, and bipolar disorder) and substance abuse because the complex cognitive features of adherence for such conditions require specific interventions that are not applicable to patients with other conditions, acute conditions because adherence for such disease differs from that for chronic illness (23), studies published before 1994 because of a large systematic review that included studies up to 1994 (24), and non–English-language and non-U.S. studies to ensure greater applicability of our findings to the unique health care setting of the United States. Other systematic reviews also note that adherence studies from non–U.S.-based health care systems are inherently different from those in the United States because of variations in the ways that patients procure, pay for, and monitor medications (2526).

Table Jump PlaceholderAppendix Table 1. 

Inclusion and Exclusion Criteria

Adherence is a complex multifactorial behavior that is influenced by social and economic factors (for example, age, race, sex, and socioeconomic status), patient-related factors (for example, knowledge, attitude, and beliefs), condition- and treatment-related factors (for example, severity of the symptoms and disease, complexity of the medical regimen, duration of treatment, and adverse effects), provider characteristics (for example, communication skills, training, and resources), and setting (for example, drug coverage, cost sharing of medications, and access to medication and clinical care) (27). Such factors interact to influence adherence behavior. For instance, the setting may influence patient and provider behavior through appointments that are too short to discuss adherence, fee structures that do not support reimbursement for patient counseling and education, poor continuity of care that disrupts the patient–provider relationship, and systems that impede information sharing between providers and pharmacists on prescription refills (27).

Hence, patient adherence behaviors in countries or settings without the systemic characteristics of the United States are markedly different. Residents of the United States have been found to be 2 to 3 times more likely to report cost-related nonadherence than Canadian residents (2829), even when the results were stratified by insurance status. Publicly or privately insured patients in the United States were more than twice as likely to report cost-related nonadherence than the reference group of patients who were seniors receiving social assistance in Ontario, Canada (29). Of note, in our review of 61 excluded non-U.S. studies, 7 were set in developing countries (3036), 1 was a multicenter trial that included developing countries (37), and the remaining 53 were set in 15 advanced economies with universal coverage of various types (3890). Of these, more than half were set in the United Kingdom (17 studies) (3854) and Canada (10 studies) (5564).

As suggested by Norris and colleagues (91), we conducted a preliminary assessment of the availability of evidence from randomized, controlled trials (RCTs) and the likelihood of selection bias and confounding from observational studies and accordingly focused on RCTs for patient, provider, and systems interventions. We expanded the scope to include observational studies for policy interventions because these studies allowed us to assess the effectiveness of policy innovations in practice settings that are not usually tested in trials.

Data Sources and Searches

To identify relevant articles, we conducted separate targeted literature searches for patient, provider, systems, and policy interventions by using MEDLINE, the Cochrane Library, and the Cochrane Central Register of Controlled Trials from 1994 through 4 June 2012. We reviewed our search strategy with a panel of technical experts and supplemented it as needed according to their recommendations. To avoid retrieval bias, we manually searched the reference lists of pertinent reviews to identify relevant citations that our searches missed.

Study Selection

Two trained researchers independently reviewed each title and abstract. All titles selected by at least 1 reviewer went on to full-text review by 2 independent reviewers. Reviewers resolved conflicts by discussion and consensus or consultation with a third reviewer as needed.

Data Extraction and Quality Assessment

For studies meeting the inclusion criteria, a trained reviewer abstracted data into structured evidence tables that were then reviewed by a second trained reviewer for completeness and accuracy.

Two independent reviewers assessed risk of bias for each study by using predefined criteria based on those developed by AHRQ (92) and specified in the RTI Item Bank (93). We resolved disagreements between reviewers by consulting a senior member of the team.

Data Analysis and Synthesis

To make the findings as clinically useful as possible, we analyzed results for each key question by both clinical condition and intervention type. We specified a priori the data to be collected for all outcomes except biomarkers and morbidity. On the basis of the recommendations of the technical expert panel, we elected to collect a comprehensive set of biomarkers and morbidity outcomes, rather than judge which to collect in advance. We determined quantitative analysis to be inappropriate because of clinical or methodological heterogeneity, low numbers of similar studies, and insufficiency or in outcome reporting, so we synthesized data qualitatively. We grouped interventions into categories that reflected key intervention components.

We graded the strength of evidence for medication adherence, biomarkers (for example, systolic blood pressure and hemoglobin A1c), morbidity (for example, depressive symptoms and asthma symptoms), mortality, and other health outcomes (94). These grades incorporate 4 key considerations when the strength of a stated effect is being evaluated: risk of bias (including study design and aggregate quality), consistency, directness, and precision (see Appendix Table 2, for definitions of strength-of-evidence grades). We excluded studies with high risk of bias and found no variation in directness. As a result, consistency and precision were key drivers of the strength-of-evidence grades in this body of studies with medium and low risk of bias.

Table Jump PlaceholderAppendix Table 2. 

Definitions of Grades of Overall Strength of Evidence

Role of the Funding Source

The AHRQ funded the systematic review. The key questions, protocol, and draft report were reviewed by the funder, the peer reviewers, the technical expert panel members, and the public. Approval from AHRQ was required before the manuscript could be submitted for publication, but the authors are solely responsible for its content and the decision to submit it for publication.

First, we present the results from our literature search and a summary of the characteristics of our included studies. We then present our results for patient, provider, and systems interventions by clinical condition and intervention type. Supplement 1 and Appendix Table 3 summarize our findings and give the strength-of-evidence grade for each intervention. Although we present our results separately by clinical condition and intervention type, the close correlation between these 2 factors requires that results synthesized by clinical condition specify intervention type. Similarly, results synthesized by intervention type specify clinical condition. Finally, we present results for policy interventions and summarize the findings in Appendix Table 4. We generally highlight evidence of moderate or low strength.

Table Jump PlaceholderAppendix Table 3. 

Summary of Strength of Evidence, by Intervention Type

Table Jump PlaceholderAppendix Table 4. 

Summary of Evidence for Policy Interventions

Characteristics of Included Studies

Of the 4124 citations identified (Appendix Figure), 758 published articles met inclusion criteria at the title and abstract review. Of these, 661 articles did not meet inclusion criteria on review of the full text. We excluded 24 additional articles with high risk of bias during data extraction. Of the 73 included articles (comprising 67 studies of low or medium risk of bias), 69 reported on RCTs and 4 reported on observational studies. Sixty-two provided data on patient, provider, and systems interventions (95162). One trial and 4 observational studies provided information on policy interventions (163167).

Grahic Jump Location
Appendix Figure.

Summary of evidence search and selection.

NA = not applicable; PICOTS = population, intervention, comparators, outcomes, timing, setting.

Grahic Jump Location

Most trials on patient, provider, or systems interventions provided information about 6 key characteristics: the targets, agents, methods, intensity, duration, and components of the interventions. The characteristics provided a framework by which we could describe the interventions. For example, for the targets, slightly more than 50% of the interventions were aimed at various combinations of multiple targets, whereas nearly 40% targeted only patients. Similarly, for delivery, a pharmacist, physician, or nurse delivered approximately 50% of interventions. About half of interventions involved at least some face-to-face delivery of the program. Supplement 2 presents information about each study's intervention, including its description, type, dose, and method of delivery.

Included trials of patient, policy, and systems interventions focus on hypertension (18 trials, 9691 patients), depression (13 trials, 11 445 patients), hyperlipidemia (9 trials, 19 228 patients), asthma (8 trials, 4423 patients), diabetes (6 trials, 1056 patients), heart failure (5 trials, 719 patients), multiple or unspecified chronic conditions (4 trials, 3403 patients), musculoskeletal diseases (4 trials, 2559 patients), myocardial infarction (1 trial, 907 patients), multiple sclerosis (1 trial, 435 patients), and glaucoma (1 trial, 66 patients). Of these, 7 studies examine more than 1 clinical condition. Fifteen studies (24%) were powered for adherence as a primary outcome (98, 107108, 124, 129, 131133, 135, 139, 153156, 159). Of note, we found no eligible studies for cancer, probably because we restricted this review to patient-administered medications in outpatient settings.

Included studies on policy interventions focus on cardiovascular disease (5 studies, >70 000 patients), diabetes (3 studies, approximately 20 000 patients), and respiratory conditions (1 study, number of patients not reported).

Effect of Patient, Provider, or Systems Interventions on Medication Adherence and Other Outcomes

Overall, the evidence from 62 trials (68 articles) suggests that many pathways provide opportunities to improve medication adherence across clinical conditions. These approaches range from low-cost, low-intensity interventions, such as 1-time mailings, to intensive interventions, such as case management, care coordination, and collaborative care.

Despite evidence for promising approaches to improving medication adherence, we found relatively little evidence linking higher adherence to improvements in other outcomes, such as biomarkers, morbidity, mortality, quality of life, patient satisfaction, health care use, or costs. Of the 62 trials, 33 (53%) reported improvement in medication adherence. Of these 33 trials, 18 (29%) reported improvements in at least 1 health outcome, 8 (13%) reported no improvements in health outcomes, and 7 (11%) did not evaluate changes in health outcomes. The remaining 29 trials (47%) showed no improvement in medication adherence.

Findings Related to Clinical Conditions
Medication Adherence.

We found evidence supporting multiple effective interventions to improve medication adherence for the following conditions: hypertension (blister packaging, case management, education with behavioral support) (109112, 116117, 122124), heart failure (reminder calls; pharmacist-led, multicomponent interventions; education with behavioral support; case management) (127130), depression (case management, collaborative care) (95, 111, 140142, 144147, 152), and asthma (self-management, shared decision making) (132137). Not all interventions in these clinical areas, however, provided evidence of benefit. We graded the strength of evidence for some interventions as insufficient because of inconsistent or statistically nonsignificant results (98, 125126, 149150). In addition, we found evidence of no benefit of collaborative care for hypertension (97, 114115) or patient or provider access to patient adherence data for asthma (138139).

With respect to diabetes, hyperlipidemia, and musculoskeletal diseases, we found evidence of 1 effective intervention for each condition. These included care coordination and collaborative care for diabetes (95), education with behavioral support for hyperlipidemia (104108), and virtual clinic for osteoporosis (157). All other intervention types studied for these clinical conditions had insufficient evidence of benefit, generally due to results that were inconsistent or not statistically significant (9899, 101103, 109, 155156).

The least evidence of improvement in medication adherence, despite multiple trials testing 2 approaches, pertained to patients with multiple chronic conditions. Three trials testing 1 approach—pharmacist-led case management—resulted in no benefit for medication adherence (159161). In addition, we judged evidence from another trial, which tested intensive interdisciplinary assessment followed by nurse-led case management, to be insufficient because the results were not statistically significant (162).

Other Health Outcomes.

We found the most consistent evidence for improved health outcomes attributable to better medication adherence for patients with hypertension, heart failure, depression, and asthma. For hypertension, both case management (96, 111112) and face-to-face education by pharmacists (109, 116117) led to enhanced adherence that decreased systolic and diastolic blood pressure. For heart failure, a pharmacist-led, multicomponent adherence intervention reduced emergency department visits and improved patient satisfaction (129). Among patients with depression, case management reduced symptoms of depression (95, 111, 140142), and collaborative care improved depression symptoms, patient satisfaction with medications, and quality of care (144147). Finally, among patients with asthma, shared decision making improved symptoms, pulmonary function, health care use, and quality of life (137). We generally graded these interventions as beneficial, with low to moderate strength of evidence, depending on the specific type of intervention. We found very little evidence supporting a relationship between improved medication adherence and adverse events (data not shown).

Findings Related to Interventions

Of the 18 intervention approaches, 7 had been tested across different clinical conditions (Appendix Table 3 and Supplement 2): education; case management; reminders; pharmacist-led, multicomponent approaches; collaborative care; telephone-based counseling, care management, and reminders; and decision aids. Of these, educational interventions with behavioral support through continued patient contact over several weeks or months (effective for hypertension [122124], hyperlipidemia [104108], heart failure [128], and myocardial infarction [131]) and case management (effective for diabetes [9597], hypertension [111112], heart failure [127], and depression [9596, 111, 140142]) offer the most voluminous and consistent evidence of improvements in medication adherence and other health outcomes across varied clinical conditions. We also found moderate-strength evidence for self-management interventions for asthma, which generally include strong educational components. Other promising approaches found to be effective in more than 1 clinical area include reminders (heart failure, depression) (130, 152) and pharmacist-led, multicomponent approaches (heart failure, glaucoma) (129, 153), but this evidence is limited to single studies in each clinical area.

Certain intervention types may provide the most benefit for patients with a specific clinical condition. Collaborative care with in-person patient visits for education and counseling seemed to be effective primarily for patients with depression or with depression and diabetes; for other clinical conditions (hyperlipidemia and hypertension), the evidence was insufficient.

Some effective interventions, such as shared decision making (137) and blister packaging (110), that were tested in only a single clinical area with a single trial may hold promise, but without additional evidence, their widespread applicability is difficult to judge. Telephone counseling, care management, and monitoring, tested under 4 clinical conditions (diabetes [100], multiple sclerosis [154], depression [149151], and musculoskeletal disease [158]), failed to show statistically significant benefit for medication adherence, except in 1 trial for patients with multiple sclerosis (154).

Effect of Policy Interventions on Medication Adherence and Other Outcomes

Five studies evaluated effects of policy interventions on adherence to medications; all 5 addressed medications used to treat cardiovascular disease (Appendix Table 4) (163167). Three of the 5 studies (163, 165, 167) also assessed adherence to medications used to treat diabetes, and 1 of the 5 studies (163) assessed adherence to medications used to treat respiratory conditions. One of the 5 studies was an RCT (166), whereas the other 4 were cohort studies. All 5 studies measured medication adherence by using insurance claims data as either the medication possession ratio or proportion of days covered. All 5 policy change interventions reduced patients' out-of-pocket expenses for prescription medications through either reduced medication copayments or improved prescription drug coverage.

All 5 studies found statistically significant between-group differences in adherence to medications for cardiovascular conditions, favoring patients whose medication copayments were reduced (163166) or whose coverage improved (167). In 2 of the cohort studies (163164), however, medication adherence to cardiovascular medicines decreased over time in all groups, although the magnitudes of between-group differences were similar to those reported in the RCT (166). Together, these results provide moderate-strength evidence that policy interventions that reduce patient out-of-pocket expenses have a beneficial effect on adherence to cardiovascular medications (Appendix Table 4).

All 3 studies that assessed adherence to medications used to treat diabetes found statistically significant between-group differences in adherence to those medicines favoring the group that had reduced out-of-pocket expenses (163, 165, 167). In 2 of the 3 studies, medication adherence decreased over time in all groups. However, the magnitude of between-group differences was similar to that in the third study, which found an increase in adherence among those with some prior coverage for prescription medications after implementation of Medicare Part D (167). Therefore, we found moderate-strength evidence for policy interventions that reduced patient out-of-pocket expenses to improve adherence to medications used to treat diabetes (Appendix Table 4).

One study found no effect of a policy intervention on adherence to inhaled corticosteroids, which are usually used to treat reactive airway disease conditions (163). Therefore, we concluded that evidence is insufficient to draw conclusions for the effectiveness of policy interventions in this clinical area.

One trial examined the effect of policy interventions on clinical outcomes (166). It found a 14% reduction in the rate of first vascular events after hospital discharge for myocardial infarction. It also found a 26% reduction in total patient spending but no change in total insurer payments. We concluded that evidence is insufficient to draw conclusions about the effect of policy interventions on clinical and economic outcomes (Appendix Table 4).

In this systematic review of patient, provider, systems, and policy interventions to improve medication adherence, we found evidence of effective interventions for many chronic conditions. Among interventions to improve medication adherence at the patient, provider, or systems level, we found the strongest evidence for improving medication adherence for self-management of asthma (in the short term) and case management or collaborative care with in-person patient education visits for depression. Among interventions to improve medication adherence at the policy level, we found robust evidence that reduced out-of-pocket expenses improved medication adherence across clinical conditions. With regard to clinical outcomes, we found the strongest evidence that improved medication adherence was accompanied by improved clinical outcomes with pharmacist-led hypertension management interventions for systolic blood pressure improvement and case management interventions for depression symptoms. We also found evidence that education with behavioral support; reminders; and pharmacist-led, multicomponent interventions enhanced adherence across more than 1 clinical area.

Our review is consistent with previous medication adherence reviews. A meta-analysis of intervention studies on medication adherence published through 1994 showed small to moderate effects of a broad range of behavioral interventions on medication adherence across multiple conditions (24), although the reviewers identified only 3 broad categories of intervention types (behavioral, educational, and “affective”) and found no differences in outcomes by intervention type. The investigators did report that multidimensional approaches were more effective than unidimensional approaches (24). A Cochrane review of studies through 2007 also showed that medication adherence interventions can have moderate effects on adherence and health outcomes for several common chronic (as well as acute) medical conditions, although this review included only adherence studies that also assessed health outcomes (6).

Our review sought to broaden understanding of the effect of interventions on adherence. It included studies from 1994 through 4 June 2012 with adherence intervention trials, even if they did not assess other health outcomes. Unlike other reviews, it examined intervention effects for specific clinical conditions and across conditions in relation to intervention type to identify those programs with the strongest evidence. It also included studies that assessed the effects of policy interventions.

Poor medication adherence produces large downstream health care costs. Thus, policymakers contemplating changes in health policy should take note of our assessment, from 5 consistent studies (moderate-strength evidence), that reducing patients' out-of-pocket costs improves medication adherence. Compared with other effective interventions, such as case management and collaborative care, which are relatively complex and labor-intensive, reducing copayments can potentially improve adherence for large numbers of geographically diverse patients.

Clinicians may be encouraged that the best evidence for improved medication adherence was present for several common conditions, including depression, hypertension, diabetes, asthma, and hyperlipidemia. However, it is also noteworthy that we found no studies that directly addressed polypharmacy and that we found either insufficient evidence or evidence of no benefit for studies of populations with multiple chronic conditions. Hence, caution must be used in extrapolating findings for 1 condition to patients with multiple comorbid conditions.

The 18 intervention clusters and characteristics we identified provide a starting framework by which practitioners and researchers may develop, test, and report their adherence programs more explicitly and consistently. The interventions we analyzed ranged from simple to complex. Decision-makers should be cautious in trying to pick components of complex interventions to enhance medication adherence. In our judgment, and as noted in a prior adherence review by Simoni and colleagues (22), sufficient information is not yet available to guide choices among the considerable array of program components. In our review, a lack of data about mediating relationships through which interventions affected adherence limited the conclusions that we could draw about the effectiveness of specific intervention components. Therefore, future studies should strive to more clearly describe each intervention component, and studies should be designed to identify which components are driving the effects of the intervention. For instance, more studies with factorial designs would help to assess both additive and multiplicative effects of intervention components. At a minimum, using guidelines from the Standards for Quality Improvement Reporting Excellence 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 (168).

Diverse interventions and varied adherence measures across studies limited our ability to pool results quantitatively. The identification and use of standardized, objective adherence measures and definitions in future research should enable investigators to pool data from such studies.

In addition to the heterogeneity of outcome measures noted, our review process and the evidence base both limit interpretations of our findings. The constraints for populations and settings that we imposed on the systematic review—such as excluding interventions for HIV, children and adolescents, and non-U.S. populations—limit its generalizability.

Although many studies were relatively small, they were conducted across many common chronic conditions affecting adults. Findings from this diverse set of clinical conditions and interventions have not been replicated in trials with larger patient populations or multiple study sites, in groups with different sociodemographic characteristics, or over longer follow-up periods. These gaps in the evidence base limit the applicability of our results.

We also limited our pool of included interventions to those designed specifically to address medication adherence as a primary or secondary outcome. We excluded clinical trials of drugs that assessed adherence to aid in the interpretation of safety and efficacy data. Thus, we did not address the comparative effectiveness of specific drug formulations in improving adherence.

We categorized patient, provider, and systems interventions by assigning labels based on short intervention descriptions that do not fully account for heterogeneity within and across clinical conditions or patient populations. Doing so allowed us to make comparisons across conditions but limited our ability to make definitive statements about intervention effectiveness across clinical areas. We believe our categories provide useful heuristics, but users should regard them more as hypothesis-generating than as an established system of classification.

Several reviews published over the past 2 decades, now complemented by our systematic review, confirm that a wide range of interventions can improve medication adherence. At this stage, new studies need to ask, “What specific elements of multicomponent interventions work best for improving medication adherence?” and, “How can we further enhance medication adherence interventions to increase adherence and ultimately improve health outcomes?”

Agency for Healthcare Research and Quality. Priority Areas for National Action: Transforming Health Care Quality. Rockville, MD: Agency for Healthcare Research and Quality; 2003.
 
Pathman DE, Konrad TR, Freed GL, Freeman VA, Koch GG. The awareness-to-adherence model of the steps to clinical guideline compliance. The case of pediatric vaccine recommendations. Med Care. 1996; 34:873-89.
PubMed
 
Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005; 353:487-97.
PubMed
CrossRef
 
World Health Organization. Noncommunicable Diseases and Mental Health: Progress Report 2002-2003. Geneva: World Health Organization; 2003.
 
Peterson AM, Takiya L, Finley R. Meta-analysis of trials of interventions to improve medication adherence. Am J Health Syst Pharm. 2003; 60:657-65.
PubMed
 
Haynes RB, Ackloo E, Sahota N, McDonald HP, Yao X. Interventions for enhancing medication adherence. Cochrane Database Syst Rev. 2008; CD000011.
PubMed
 
World Health Organization. The World Health Report 2002: Reducing Risks, Promoting Healthy Life. Geneva: World Health Organization; 2002.
 
World Health Organization. Adherence to Long-Term Therapies: Evidence for Action. Geneva: World Health Organization; 2003.
 
Dunbar-Jacob J, Erlen JA, Schlenk EA, Ryan CM, Sereika SM, Doswell WM. Adherence in chronic disease. Annu Rev Nurs Res. 2000; 18:48-90.
PubMed
 
Sarquis LM, Dellácqua MC, Gallani MC, Moreira RM, Bocchi SC, Tase TH, et al. [Compliance in antihypertensive therapy: analyses in scientific articles]. Rev Esc Enferm USP. 1998; 32:335-53.
PubMed
 
DiMatteo MR, Giordani PJ, Lepper HS, Croghan TW. Patient adherence and medical treatment outcomes: a meta-analysis. Med Care. 2002; 40:794-811.
PubMed
 
Schiff GD, Fung S, Speroff T, McNutt RA. Decompensated heart failure: symptoms, patterns of onset, and contributing factors. Am J Med. 2003; 114:625-30.
PubMed
CrossRef
 
Waeber B, Burnier M, Brunner HR. How to improve adherence with prescribed treatment in hypertensive patients? J Cardiovasc Pharmacol. 2000; 35:Suppl 3S23-6.
PubMed
CrossRef
 
Psaty BM, Koepsell TD, Wagner EH, LoGerfo JP, Inui TS. The relative risk of incident coronary heart disease associated with recently stopping the use of beta-blockers. JAMA. 1990; 263:1653-7.
PubMed
CrossRef
 
Beckles GL, Engelgau MM, Narayan KM, Herman WH, Aubert RE, Williamson DF. Population-based assessment of the level of care among adults with diabetes in the U.S. Diabetes Care. 1998; 21:1432-8.
PubMed
CrossRef
 
Rogers PG, Bullman W. Prescription medicine compliance: review of the baseline of knowledge—report of the National Council on Patient Information and Education. Journal of Pharmacoepidemiology. 1995; 3:3-36.
 
Mahoney JJ, Ansell BJ, Fleming WK, Butterworth SW. The unhidden cost of noncompliance. J Manag Care Pharm. 2008; 14:S1-S29.
 
New England Healthcare Institute. Thinking Outside the Pillbox: A System-wide Approach to Improving Patient Medication Adherence for Chronic Disease. Cambridge, MA: New England Healthcare Institute; 2009.
 
Showalter A. Costs of Patient Noncompliance. Crystal Lake, IL: AlignMap; 2006; 1-4.
 
Task Force for Compliance. Noncompliance with Medications: An Economic Tragedy with Important Implications for Health Care Reform. Washington, DC: Task Force for Compliance; 1994.
 
Shojania KG, McDonald KM, Wachter R, Owens DK. Closing the Quality Gap: A Critical Analysis of Quality Improvement Strategies: Volume 1—Series Overview and Methodology. AHRQ publication no. 04-0051-1. (Prepared by the Stanford University-UCSF Evidence-based Practice Center under contract 290-02-0017.). Rockville, MD: Agency for Healthcare Research and Quality; 2004.
 
Simoni JM, Pearson CR, Pantalone DW, Marks G, Crepaz N. Efficacy of interventions in improving highly active antiretroviral therapy adherence and HIV-1 RNA viral load. A meta-analytic review of randomized controlled trials. J Acquir Immune Defic Syndr. 2006; 43:Suppl 1S23-35.
PubMed
CrossRef
 
Rueda S, Park-Wyllie LY, Bayoumi AM, Tynan AM, Antoniou TA, Rourke SB, et al. Patient support and education for promoting adherence to highly active antiretroviral therapy for HIV/AIDS. Cochrane Database Syst Rev. 2006; CD001442.
PubMed
 
Roter DL, Hall JA, Merisca R, Nordstrom B, Cretin D, Svarstad B. Effectiveness of interventions to improve patient compliance: a meta-analysis. Med Care. 1998; 36:1138-61.
PubMed
CrossRef
 
Gellad WF, Grenard JL, Marcum ZA. A systematic review of barriers to medication adherence in the elderly: looking beyond cost and regimen complexity. Am J Geriatr Pharmacother. 2011; 9:11-23.
PubMed
CrossRef
 
Grenard JL, Munjas BA, Adams JL, Suttorp M, Maglione M, McGlynn EA, et al. Depression and medication adherence in the treatment of chronic diseases in the United States: a meta-analysis. J Gen Intern Med. 2011; 26:1175-82.
PubMed
CrossRef
 
Briesacher BA, Gurwitz JH, Soumerai SB. Patients at-risk for cost-related medication nonadherence: a review of the literature. J Gen Intern Med. 2007; 22:864-71.
PubMed
CrossRef
 
Kennedy J, Morgan S. A cross-national study of prescription nonadherence due to cost: data from the Joint Canada-United States Survey of Health. Clin Ther. 2006; 28:1217-24.
PubMed
CrossRef
 
Kennedy J, Morgan S. Cost-related prescription nonadherence in the United States and Canada: a system-level comparison using the 2007 International Health Policy Survey in Seven Countries. Clin Ther. 2009; 31:213-9.
PubMed
 
Bocchi EA, Cruz F, Guimarães G, Pinho Moreira LF, Issa VS, Ayub Ferreira SM, et al. Long-term prospective, randomized, controlled study using repetitive education at six-month intervals and monitoring for adherence in heart failure outpatients: the REMADHE trial. Circ Heart Fail. 2008; 1:115-24.
PubMed
CrossRef
 
de Castro MS, Fuchs FD, Santos MC, Maximiliano P, Gus M, Moreira LB, et al. Pharmaceutical care program for patients with uncontrolled hypertension. Report of a double-blind clinical trial with ambulatory blood pressure monitoring. Am J Hypertens. 2006; 19:528-33.
PubMed
 
Ponnusankar S, Surulivelrajan M, Anandamoorthy N, Suresh B. Assessment of impact of medication counseling on patients' medication knowledge and compliance in an outpatient clinic in South India. Patient Educ Couns. 2004; 54:55-60.
PubMed
CrossRef
 
Seck BC, Jackson RT. Determinants of compliance with iron supplementation among pregnant women in Senegal. Public Health Nutr. 2008; 11:596-605.
PubMed
CrossRef
 
Stewart A, Noakes T, Eales C, Shepard K, Becker P, Veriawa Y. Adherence to cardiovascular risk factor modification in patients with hypertension. Cardiovasc J S Afr. 2005; 16:102-7.
PubMed
 
Phumipamorn S, Pongwecharak J, Soorapan S, Pattharachayakul S. Effects of the pharmacist's input on glycaemic control and cardiovascular risks in Muslim diabetes. Prim Care Diabetes. 2008; 2:31-7.
PubMed
CrossRef
 
Sookaneknun P, Richards RM, Sanguansermsri J, Teerasut C. Pharmacist involvement in primary care improves hypertensive patient clinical outcomes. Ann Pharmacother. 2004; 38:2023-8.
PubMed
CrossRef
 
Delmas PD, Vrijens B, Eastell R, Roux C, Pols HA, Ringe JD, et al, Improving Measurements of Persistence on Actonel Treatment (IMPACT) Investigators. Effect of monitoring bone turnover markers on persistence with risedronate treatment of postmenopausal osteoporosis. J Clin Endocrinol Metab. 2007; 92:1296-304.
PubMed
CrossRef
 
Sovani MP, Whale CI, Oborne J, Cooper S, Mortimer K, Ekström T, et al. Poor adherence with inhaled corticosteroids for asthma: can using a single inhaler containing budesonide and formoterol help? Br J Gen Pract. 2008; 58:37-43.
PubMed
CrossRef
 
Perahia DG, Quail D, Gandhi P, Walker DJ, Peveler RC. A randomized, controlled trial of duloxetine alone vs. duloxetine plus a telephone intervention in the treatment of depression. J Affect Disord. 2008; 108:33-41.
PubMed
CrossRef
 
Atherton-Naji A, Hamilton R, Riddle W, Naji S. Improving adherence to antidepressant drug treatment in primary care: a feasibility study for a randomized controlled trial of educational intervention. Primary Care Psychiatry. 2001; 7:61-7.
CrossRef
 
Claxton A, de Klerk E, Parry M, Robinson JM, Schmidt ME. Patient compliance to a new enteric-coated weekly formulation of fluoxetine during continuation treatment of major depressive disorder. J Clin Psychiatry. 2000; 61:928-32.
PubMed
CrossRef
 
Peveler R, George C, Kinmonth AL, Campbell M, Thompson C. Effect of antidepressant drug counselling and information leaflets on adherence to drug treatment in primary care: randomised controlled trial. BMJ. 1999; 319:612-5.
PubMed
CrossRef
 
Nazareth I, Burton A, Shulman S, Smith P, Haines A, Timberal H. A pharmacy discharge plan for hospitalized elderly patients—a randomized controlled trial. Age Ageing. 2001; 30:33-40.
PubMed
CrossRef
 
Begley S, Livingstone C, Hodges N, Williamson V. Impact of domiciliary pharmacy visits on medication management in an elderly population. Int J Pharm Pract. 1997; 5:111-21.
CrossRef
 
Brown I, Sheeran P, Reuber M. Enhancing antiepileptic drug adherence: a randomized controlled trial. Epilepsy Behav. 2009; 16:634-9.
PubMed
CrossRef
 
Goodyer LI, Miskelly F, Milligan P. Does encouraging good compliance improve patients' clinical condition in heart failure? Br J Clin Pract. 1995; 49:173-6.
PubMed
 
Cooper A, Drake J, Brankin E, PERSIST Investigators. Treatment persistence with once-monthly ibandronate and patient support vs. once-weekly alendronate: results from the PERSIST study. Int J Clin Pract. 2006; 60:896-905.
PubMed
CrossRef
 
Clowes JA, Peel NF, Eastell R. The impact of monitoring on adherence and persistence with antiresorptive treatment for postmenopausal osteoporosis: a randomized controlled trial. J Clin Endocrinol Metab. 2004; 89:1117-23.
PubMed
CrossRef
 
Grosset KA, Grosset DG. Effect of educational intervention on medication timing in Parkinson's disease: a randomized controlled trial. BMC Neurol. 2007; 7:20.
PubMed
CrossRef
 
Hardstaff R, Green K, Talbot D. Measurement of compliance posttransplantation—the results of a 12-month study using electronic monitoring. Transplant Proc. 2003; 35:796-7.
PubMed
CrossRef
 
Homer D, Nightingale P, Jobanputra P. Providing patients with information about disease-modifying anti-rheumatic drugs: Individually or in groups? A pilot randomized controlled trial comparing adherence and satisfaction. Musculoskeletal Care. 2009; 7:78-92.
PubMed
CrossRef
 
Hill J, Bird H, Johnson S. Effect of patient education on adherence to drug treatment for rheumatoid arthritis: a randomised controlled trial. Ann Rheum Dis. 2001; 60:869-75.
PubMed
 
Sturgess IK, McElnay JC, Hughes CM, Crealey G. Community pharmacy based provision of pharmaceutical care to older patients. Pharm World Sci. 2003; 25:218-26.
PubMed
CrossRef
 
Varma S, McElnay JC, Hughes CM, Passmore AP, Varma M. Pharmaceutical care of patients with congestive heart failure: interventions and outcomes. Pharmacotherapy. 1999; 19:860-9.
PubMed
CrossRef
 
Coté J, Cartier A, Robichaud P, Boutin H, Malo JL, Rouleau M, et al. Influence on asthma morbidity of asthma education programs based on self-management plans following treatment optimization. Am J Respir Crit Care Med. 1997; 155:1509-14.
PubMed
 
Côté J, Bowie DM, Robichaud P, Parent JG, Battisti L, Boulet LP. Evaluation of two different educational interventions for adult patients consulting with an acute asthma exacerbation. Am J Respir Crit Care Med. 2001; 163:1415-9.
PubMed
 
Tamblyn R, Reidel K, Huang A, Taylor L, Winslade N, Bartlett G, et al. Increasing the detection and response to adherence problems with cardiovascular medication in primary care through computerized drug management systems: a randomized controlled trial. Med Decis Making. 2010; 30:176-88.
PubMed
CrossRef
 
Gwadry-Sridhar FH, Arnold JM, Zhang Y, Brown JE, Marchiori G, Guyatt G. Pilot study to determine the impact of a multidisciplinary educational intervention in patients hospitalized with heart failure. Am Heart J. 2005; 150:982.
PubMed
CrossRef
 
Tsuyuki RT, Fradette M, Johnson JA, Bungard TJ, Eurich DT, Ashton T, et al. A multicenter disease management program for hospitalized patients with heart failure. J Card Fail. 2004; 10:473-80.
PubMed
CrossRef
 
Rinfret S, Lussier MT, Peirce A, Duhamel F, Cossette S, Lalonde L, et al, LOYAL Study Investigators. The impact of a multidisciplinary information technology-supported program on blood pressure control in primary care. Circ Cardiovasc Qual Outcomes. 2009; 2:170-7.
PubMed
CrossRef
 
Edworthy SM, Baptie B, Galvin D, Brant RF, Churchill-Smith T, Manyari D, et al. Effects of an enhanced secondary prevention program for patients with heart disease: a prospective randomized trial. Can J Cardiol. 2007; 23:1066-72.
PubMed
CrossRef
 
Leenen FH, Wilson TW, Bolli P, Larochelle P, Myers M, Handa SP, et al. Patterns of compliance with once versus twice daily antihypertensive drug therapy in primary care: a randomized clinical trial using electronic monitoring. Can J Cardiol. 1997; 13:914-20.
PubMed
 
Waters BM, Jensen L, Fedorak RN. Effects of formal education for patients with inflammatory bowel disease: a randomized controlled trial. Can J Gastroenterol. 2005; 19:235-44.
PubMed
 
Sherrard H, Struthers C, Kearns SA, Wells G, Chen L, Mesana T. Using technology to create a medication safety net for cardiac surgery patients: a nurse-led randomized control trial. Can J Cardiovasc Nurs. 2009; 19:9-15.
PubMed
 
Peterson GM, Fitzmaurice KD, Naunton M, Vial JH, Stewart K, Krum H. Impact of pharmacist-conducted home visits on the outcomes of lipid-lowering drug therapy. J Clin Pharm Ther. 2004; 29:23-30.
PubMed
CrossRef
 
Vrijens B, Goetghebeur E. Comparing compliance patterns between randomized treatments. Control Clin Trials. 1997; 18:187-203.
PubMed
CrossRef
 
Rubak S, Sandbæk A, Lauritzen T, Borch-Johnsen K, Christensen B. Effect of “motivational interviewing” on quality of care measures in screen detected type 2 diabetes patients: a one-year follow-up of an RCT, ADDITION Denmark. Scand J Prim Health Care. 2011; 29:92-8.
PubMed
CrossRef
 
Christensen A, Christrup LL, Fabricius PE, Chrostowska M, Wronka M, Narkiewicz K, et al. The impact of an electronic monitoring and reminder device on patient compliance with antihypertensive therapy: a randomized controlled trial. J Hypertens. 2010; 28:194-200.
PubMed
CrossRef
 
Hornnes N, Larsen K, Boysen G. Blood pressure 1 year after stroke: the need to optimize secondary prevention. J Stroke Cerebrovasc Dis. 2011; 20:16-23.
PubMed
CrossRef
 
Nielsen D, Ryg J, Nielsen W, Knold B, Nissen N, Brixen K. Patient education in groups increases knowledge of osteoporosis and adherence to treatment: a two-year randomized controlled trial. Patient Educ Couns. 2010; 81:155-60.
PubMed
CrossRef
 
Brus HL, van de Laar MA, Taal E, Rasker JJ, Wiegman O. Effects of patient education on compliance with basic treatment regimens and health in recent onset active rheumatoid arthritis. Ann Rheum Dis. 1998; 57:146-51.
PubMed
CrossRef
 
Elkjaer M, Shuhaibar M, Burisch J, Bailey Y, Scherfig H, Laugesen B, et al. E-health empowers patients with ulcerative colitis: a randomised controlled trial of the web-guided ‘Constant-care’ approach. Gut. 2010; 59:1652-61.
PubMed
CrossRef
 
Billault B, Degoulet P, Devries C, Plouin PF, Chatellier G, Menard J. Use of a standardized personal medical record by patients with hypertension: a randomized controlled prospective trial. MD Comput. 1995; 12:31-5.
PubMed
 
Andrejak M, Genes N, Vaur L, Poncelet P, Clerson P, Carré A. Electronic pill-boxes in the evaluation of antihypertensive treatment compliance: comparison of once daily versus twice daily regimen. Am J Hypertens. 2000; 13:184-90.
PubMed
CrossRef
 
Boissel JP, Meillard O, Perrin-Fayolle E, Ducruet T, Alamercery Y, Sassano P, et al. Comparison between a bid and a tid regimen: improved compliance with no improved antihypertensive effect. The EOL Research Group. Eur J Clin Pharmacol. 1996; 50:63-7.
PubMed
CrossRef
 
Gensichen J, von Korff M, Peitz M, Muth C, Beyer M, Güthlin C, et al, PRoMPT (PRimary care Monitoring for depressive Patients Trial). Case management for depression by health care assistants in small primary care practices: a cluster randomized trial. Ann Intern Med. 2009; 151:369-78.
PubMed
CrossRef
 
Mengden T, Vetter H, Tousset E, Uen S. Management of patients with uncontrolled arterial hypertension—the role of electronic compliance monitoring, 24-h ambulatory blood pressure monitoring and Candesartan/HCTZ. BMC Cardiovasc Disord. 2006; 6:36.
PubMed
CrossRef
 
Klein A, Otto G, Krämer I. Impact of a pharmaceutical care program on liver transplant patients' compliance with immunosuppressive medication: a prospective, randomized, controlled trial using electronic monitoring. Transplantation. 2009; 87:839-47.
PubMed
CrossRef
 
Wong FK, Chow SK, Chan TM. Evaluation of a nurse-led disease management programme for chronic kidney disease: a randomized controlled trial. Int J Nurs Stud. 2010; 47:268-78.
PubMed
 
Wu JY, Leung WY, Chang S, Lee B, Zee B, Tong PC, et al. Effectiveness of telephone counselling by a pharmacist in reducing mortality in patients receiving polypharmacy: randomised controlled trial. BMJ. 2006; 333:522.
PubMed
CrossRef
 
Vergouwen AC, Bakker A, Burger H, Verheij TJ, Koerselman F. A cluster randomized trial comparing two interventions to improve treatment of major depression in primary care. Psychol Med. 2005; 35:25-33.
PubMed
CrossRef
 
Eussen SR, van der Elst ME, Klungel OH, Rompelberg CJ, Garssen J, Oosterveld MH, et al. A pharmaceutical care program to improve adherence to statin therapy: a randomized controlled trial. Ann Pharmacother. 2010; 44:1905-13.
PubMed
CrossRef
 
Charles T, Quinn D, Weatherall M, Aldington S, Beasley R, Holt S. An audiovisual reminder function improves adherence with inhaled corticosteroid therapy in asthma. J Allergy Clin Immunol. 2007; 119:811-6.
PubMed
CrossRef
 
Gallefoss F, Bakke PS. How does patient education and self-management among asthmatics and patients with chronic obstructive pulmonary disease affect medication? Am J Respir Crit Care Med. 1999; 160:2000-5.
PubMed
CrossRef
 
López-Viña A, del Castillo-Arévalo E. Influence of peak expiratory flow monitoring on an asthma self-management education programme. Respir Med. 2000; 94:760-6.
PubMed
CrossRef
 
López Cabezas C, Falces Salvador C, Cubí Quadrada D, Arnau Bartés A, Ylla Boré M, Muro Perea N, et al. Randomized clinical trial of a postdischarge pharmaceutical care program vs regular follow-up in patients with heart failure. Farm Hosp. 2006; 30:328-42.
PubMed
CrossRef
 
Pladevall M, Brotons C, Gabriel R, Arnau A, Suarez C, de la Figuera M, et al, Writing Committee on behalf of the COM99 Study Group. Multicenter cluster-randomized trial of a multifactorial intervention to improve antihypertensive medication adherence and blood pressure control among patients at high cardiovascular risk (the COM99 study). Circulation. 2010; 122:1183-91.
PubMed
CrossRef
 
Amado Guirado E, Pujol Ribera E, Pacheco Huergo V, Borras JM, ADIEHTA Group. Knowledge and adherence to antihypertensive therapy in primary care: results of a randomized trial. Gac Sanit. 2011; 25:62-7.
PubMed
CrossRef
 
Akerblad AC, Bengtsson F, Ekselius L, von Knorring L. Effects of an educational compliance enhancement programme and therapeutic drug monitoring on treatment adherence in depressed patients managed by general practitioners. Int Clin Psychopharmacol. 2003; 18:347-54.
PubMed
 
Chen SY, Sheu S, Chang CS, Wang TH, Huang MS. The effects of the self-efficacy method on adult asthmatic patient self-care behavior. J Nurs Res. 2010; 18:266-74.
PubMed
 
Norris SL, Atkins D, Bruening W, Fox S, Johnson E, Kane R, et al. Observational studies in systemic reviews of comparative effectiveness: AHRQ and the Effective Health Care Program. J Clin Epidemiol. 2011; 64:1178-86.
PubMed
 
Agency for Healthcare Research and Quality. Methods Guide for Effectiveness and Comparative Effectiveness Reviews. Rockville, MD: Agency for Healthcare Research and Quality; 2011.
 
Viswanathan M, Berkman ND. Development of the RTI item bank on risk of bias and precision of observational studies. J Clin Epidemiol. 2012; 65:163-78.
PubMed
CrossRef
 
Owens DK, Lohr KN, Atkins D, Treadwell JR, Reston JT, Bass EB, et al. AHRQ series paper 5: grading the strength of a body of evidence when comparing medical interventions—Agency for Healthcare Research and Quality and the Effective Health-Care Program. J Clin Epidemiol. 2010; 63:513-23.
PubMed
CrossRef
 
Bogner HR, de Vries HF. Integrating type 2 diabetes mellitus and depression treatment among African Americans: a randomized controlled pilot trial. Diabetes Educ. 2010; 36:284-92.
PubMed
CrossRef
 
Bogner HR, Morales KH, de Vries HF, Cappola AR. Integrated management of type 2 diabetes mellitus and depression treatment to improve medication adherence: a randomized controlled trial. Ann Fam Med. 2012; 10:15-22.
PubMed
CrossRef
 
Lin EH, Katon W, Rutter C, Simon GE, Ludman EJ, Von Korff M, et al. Effects of enhanced depression treatment on diabetes self-care. Ann Fam Med. 2006; 4:46-53.
PubMed
CrossRef
 
Pearce KA, Love MM, Shelton BJ, Schoenberg NE, Williamson MA, Barron MA, et al, Kentucky Ambulatory Network. Cardiovascular risk education and social support (CaRESS): report of a randomized controlled trial from the Kentucky Ambulatory Network (KAN). J Am Board Fam Med. 2008; 21:269-81.
PubMed
CrossRef
 
Wolever RQ, Dreusicke M, Fikkan J, Hawkins TV, Yeung S, Wakefield J, et al. Integrative health coaching for patients with type 2 diabetes: a randomized clinical trial. Diabetes Educ. 2010; 36:629-39.
PubMed
CrossRef
 
Grant RW, Devita NG, Singer DE, Meigs JB. Improving adherence and reducing medication discrepancies in patients with diabetes. Ann Pharmacother. 2003; 37:962-9.
PubMed
CrossRef
 
Mann DM, Ponieman D, Montori VM, Arciniega J, McGinn T. The Statin Choice decision aid in primary care: a randomized trial. Patient Educ Couns. 2010; 80:138-40.
PubMed
CrossRef
 
Weymiller AJ, Montori VM, Jones LA, Gafni A, Guyatt GH, Bryant SC, et al. Helping patients with type 2 diabetes mellitus make treatment decisions: statin choice randomized trial. Arch Intern Med. 2007; 167:1076-82.
PubMed
CrossRef
 
Jones LA, Weymiller AJ, Shah N, Bryant SC, Christianson TJ, Guyatt GH, et al. Should clinicians deliver decision aids? Further exploration of the statin choice randomized trial results. Med Decis Making. 2009; 29:468-74.
PubMed
CrossRef
 
Guthrie RM. The effects of postal and telephone reminders on compliance with pravastatin therapy in a national registry: results of the first myocardial infarction risk reduction program. Clin Ther. 2001; 23:970-80.
PubMed
CrossRef
 
Johnson SS, Driskell MM, Johnson JL, Dyment SJ, Prochaska JO, Prochaska JM, et al. Transtheoretical model intervention for adherence to lipid-lowering drugs. Dis Manag. 2006; 9:102-14.
PubMed
 
Powell KM, Edgren B. Failure of educational videotapes to improve medication compliance in a health maintenance organization. Am J Health Syst Pharm. 1995; 52:2196-9.
PubMed
 
Schectman G, Hiatt J, Hartz A. Telephone contacts do not improve adherence to niacin or bile acid sequestrant therapy. Ann Pharmacother. 1994; 28:29-35.
PubMed
 
Stacy JN, Schwartz SM, Ershoff D, Shreve MS. Incorporating tailored interactive patient solutions using interactive voice response technology to improve statin adherence: results of a randomized clinical trial in a managed care setting. Popul Health Manag. 2009; 12:241-54.
PubMed
CrossRef
 
Lee JK, Grace KA, Taylor AJ. Effect of a pharmacy care program on medication adherence and persistence, blood pressure, and low-density lipoprotein cholesterol: a randomized controlled trial. JAMA. 2006; 296:2563-71.
PubMed
 
Schneider PJ, Murphy JE, Pedersen CA. Impact of medication packaging on adherence and treatment outcomes in older ambulatory patients. J Am Pharm Assoc (2003). 2008; 48:58-63.
PubMed
 
Bogner HR, de Vries HF. Integration of depression and hypertension treatment: a pilot, randomized controlled trial. Ann Fam Med. 2008; 6:295-301.
PubMed
CrossRef
 
Rudd P, Miller NH, Kaufman J, Kraemer HC, Bandura A, Greenwald G, et al. Nurse management for hypertension. A systems approach. Am J Hypertens. 2004; 17:921-7.
PubMed
 
Wakefield BJ, Holman JE, Ray A, Scherubel M, Adams MR, Hillis SL, et al. Effectiveness of home telehealth in comorbid diabetes and hypertension: a randomized, controlled trial. Telemed J E Health. 2011; 17:254-61.
PubMed
CrossRef
 
Carter BL, Ardery G, Dawson JD, James PA, Bergus GR, Doucette WR, et al. Physician and pharmacist collaboration to improve blood pressure control. Arch Intern Med. 2009; 169:1996-2002.
PubMed
CrossRef
 
Hunt JS, Siemienczuk J, Pape G, Rozenfeld Y, MacKay J, LeBlanc BH, et al. A randomized controlled trial of team-based care: impact of physician-pharmacist collaboration on uncontrolled hypertension. J Gen Intern Med. 2008; 23:1966-72.
PubMed
CrossRef
 
Solomon DK, Portner TS, Bass GE, Gourley DR, Gourley GA, Holt JM, et al. Clinical and economic outcomes in the hypertension and COPD arms of a multicenter outcomes study. J Am Pharm Assoc (Wash). 1998; 38:574-85.
PubMed
 
Gourley GA, Portner TS, Gourley DR, Rigolosi EL, Holt JM, Solomon DK, et al. Humanistic outcomes in the hypertension and COPD arms of a multicenter outcomes study. J Am Pharm Assoc (Wash). 1998; 38:586-97.
PubMed
 
Vivian EM. Improving blood pressure control in a pharmacist-managed hypertension clinic. Pharmacotherapy. 2002; 22:1533-40.
PubMed
CrossRef
 
Bosworth HB, Olsen MK, Neary A, Orr M, Grubber J, Svetkey L, et al. Take Control of Your Blood Pressure (TCYB) study: a multifactorial tailored behavioral and educational intervention for achieving blood pressure control. Patient Educ Couns. 2008; 70:338-47.
PubMed
CrossRef
 
Bosworth HB, Olsen MK, Dudley T, Orr M, Neary A, Harrelson M, et al. The Take Control of Your Blood Pressure (TCYB) study: study design and methodology. Contemp Clin Trials. 2007; 28:33-47.
PubMed
CrossRef
 
Bosworth HB, Olsen MK, Gentry P, Orr M, Dudley T, McCant F, et al. Nurse administered telephone intervention for blood pressure control: a patient-tailored multifactorial intervention. Patient Educ Couns. 2005; 57:5-14.
PubMed
CrossRef
 
Friedman RH, Kazis LE, Jette A, Smith MB, Stollerman J, Torgerson J, et al. A telecommunications system for monitoring and counseling patients with hypertension. Impact on medication adherence and blood pressure control. Am J Hypertens. 1996; 9:285-92.
PubMed
CrossRef
 
Johnson SS, Driskell MM, Johnson JL, Prochaska JM, Zwick W, Prochaska JO. Efficacy of a transtheoretical model-based expert system for antihypertensive adherence. Dis Manag. 2006; 9:291-301.
PubMed
 
Ogedegbe GO, Boutin-Foster C, Wells MT, Allegrante JP, Isen AM, Jobe JB, et al. A randomized controlled trial of positive-affect intervention and medication adherence in hypertensive African Americans. Arch Intern Med. 2012; 172:322-6.
PubMed
CrossRef
 
Powers BJ, Danus S, Grubber JM, Olsen MK, Oddone EZ, Bosworth HB. The effectiveness of personalized coronary heart disease and stroke risk communication. Am Heart J. 2011; 161:673-80.
PubMed
CrossRef
 
Ross SE, Moore LA, Earnest MA, Wittevrongel L, Lin CT. Providing a web-based online medical record with electronic communication capabilities to patients with congestive heart failure: randomized trial. J Med Internet Res. 2004; 6:12.
PubMed
CrossRef
 
Rich MW, Gray DB, Beckham V, Wittenberg C, Luther P. Effect of a multidisciplinary intervention on medication compliance in elderly patients with congestive heart failure. Am J Med. 1996; 101:270-6.
PubMed
CrossRef
 
Wu JR, Corley DJ, Lennie TA, Moser DK. Effect of a medication-taking behavior feedback theory-based intervention on outcomes in patients with heart failure. J Card Fail. 2012; 18:1-9.
PubMed
CrossRef
 
Murray MD, Young J, Hoke S, Tu W, Weiner M, Morrow D, et al. Pharmacist intervention to improve medication adherence in heart failure: a randomized trial. Ann Intern Med. 2007; 146:714-25.
PubMed
CrossRef
 
Fulmer TT, Feldman PH, Kim TS, Carty B, Beers M, Molina M, et al. An intervention study to enhance medication compliance in community-dwelling elderly individuals. J Gerontol Nurs. 1999; 25:6-14.
PubMed
 
Smith DH, Kramer JM, Perrin N, Platt R, Roblin DW, Lane K, et al.  A randomized trial of direct-to-patient communication to enhance adherence to beta-blocker therapy following myocardial infarction. Arch Intern Med. 2008;168:477-83; discussion 483; quiz 447. [PMID: 18332291]
 
Bender BG, Apter A, Bogen DK, Dickinson P, Fisher L, Wamboldt FS, et al. Test of an interactive voice response intervention to improve adherence to controller medications in adults with asthma. J Am Board Fam Med. 2010; 23:159-65.
PubMed
CrossRef
 
Berg J, Dunbar-Jacob J, Sereika SM. An evaluation of a self-management program for adults with asthma. Clin Nurs Res. 1997; 6:225-38.
PubMed
CrossRef
 
Janson SL, Fahy JV, Covington JK, Paul SM, Gold WM, Boushey HA. Effects of individual self-management education on clinical, biological, and adherence outcomes in asthma. Am J Med. 2003; 115:620-6.
PubMed
CrossRef
 
Janson SL, McGrath KW, Covington JK, Cheng SC, Boushey HA. Individualized asthma self-management improves medication adherence and markers of asthma control. J Allergy Clin Immunol. 2009; 123:840-6.
PubMed
CrossRef
 
Schaffer SD, Tian L. Promoting adherence: effects of theory-based asthma education. Clin Nurs Res. 2004; 13:69-89.
PubMed
CrossRef
 
Wilson SR, Strub P, Buist AS, Knowles SB, Lavori PW, Lapidus J, et al, Better Outcomes of Asthma Treatment (BOAT) Study Group. Shared treatment decision making improves adherence and outcomes in poorly controlled asthma. Am J Respir Crit Care Med. 2010; 181:566-77.
PubMed
CrossRef
 
Williams LK, Peterson EL, Wells K, Campbell J, Wang M, Chowdhry VK, et al. A cluster-randomized trial to provide clinicians inhaled corticosteroid adherence information for their patients with asthma. J Allergy Clin Immunol. 2010; 126:225-31, 231.e1-4.
PubMed
CrossRef
 
Weinberger M, Murray MD, Marrero DG, Brewer N, Lykens M, Harris LE, et al. Effectiveness of pharmacist care for patients with reactive airways disease: a randomized controlled trial. JAMA. 2002; 288:1594-602.
PubMed
CrossRef
 
Katon W, Rutter C, Ludman EJ, Von Korff M, Lin E, Simon G, et al. A randomized trial of relapse prevention of depression in primary care. Arch Gen Psychiatry. 2001; 58:241-7.
PubMed
CrossRef
 
Ludman E, Katon W, Bush T, Rutter C, Lin E, Simon G, et al. Behavioural factors associated with symptom outcomes in a primary care-based depression prevention intervention trial. Psychol Med. 2003; 33:1061-70.
PubMed
CrossRef
 
Von Korff M, Katon W, Rutter C, Ludman E, Simon G, Lin E, et al. Effect on disability outcomes of a depression relapse prevention program. Psychosom Med. 2003; 65:938-43.
PubMed
CrossRef
 
Capoccia KL, Boudreau DM, Blough DK, Ellsworth AJ, Clark DR, Stevens NG, et al. Randomized trial of pharmacist interventions to improve depression care and outcomes in primary care. Am J Health Syst Pharm. 2004; 61:364-72.
PubMed
 
Katon W, Von Korff M, Lin E, Walker E, Simon GE, Bush T, et al. Collaborative management to achieve treatment guidelines. Impact on depression in primary care. JAMA. 1995; 273:1026-31.
PubMed
CrossRef
 
Katon W, Robinson P, Von Korff M, Lin E, Bush T, Ludman E, et al. A multifaceted intervention to improve treatment of depression in primary care. Arch Gen Psychiatry. 1996; 53:924-32.
PubMed
CrossRef
 
Katon W, Von Korff M, Lin E, Simon G, Walker E, Unützer J, et al. Stepped collaborative care for primary care patients with persistent symptoms of depression: a randomized trial. Arch Gen Psychiatry. 1999; 56:1109-15.
PubMed
CrossRef
 
Katon W, Russo J, Von Korff M, Lin E, Simon G, Bush T, et al. Long-term effects of a collaborative care intervention in persistently depressed primary care patients. J Gen Intern Med. 2002; 17:741-8.
PubMed
CrossRef
 
Pyne JM, Fortney JC, Curran GM, Tripathi S, Atkinson JH, Kilbourne AM, et al. Effectiveness of collaborative care for depression in human immunodeficiency virus clinics. Arch Intern Med. 2011; 171:23-31.
PubMed
 
Rickles NM, Svarstad BL, Statz-Paynter JL, Taylor LV, Kobak KA. Pharmacist telemonitoring of antidepressant use: effects on pharmacist-patient collaboration. J Am Pharm Assoc (2003). 2005; 45:344-53.
PubMed
 
Simon GE, Ludman EJ, Operskalski BH. Randomized trial of a telephone care management program for outpatients starting antidepressant treatment. Psychiatr Serv. 2006; 57:1441-5.
PubMed
CrossRef
 
Simon GE, Ludman EJ, Tutty S, Operskalski B, Von Korff M. Telephone psychotherapy and telephone care management for primary care patients starting antidepressant treatment: a randomized controlled trial. JAMA. 2004; 292:935-42.
PubMed
 
Hoffman L, Enders J, Luo J, Segal R, Pippins J, Kimberlin C. Impact of an antidepressant management program on medication adherence. Am J Manag Care. 2003; 9:70-80.
PubMed
 
Okeke CO, Quigley HA, Jampel HD, Ying GS, Plyler RJ, Jiang Y, et al. Interventions improve poor adherence with once daily glaucoma medications in electronically monitored patients. Ophthalmology. 2009; 116:2286-93.
PubMed
 
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; 45:466-72.
PubMed
 
Montori VM, Shah ND, Pencille LJ, Branda ME, VanHouten HK, Swiglo BA, et al. Use of a decision aid to improve treatment decisions in osteoporosis: the osteoporosis choice randomized trial. Am J Med. 2011; 124:549-56.
PubMed
CrossRef
 
Rudd RE, Blanch DC, Gall V, Chibnik LB, Wright EA, Reichmann W, et al. A randomized controlled trial of an intervention to reduce low literacy barriers in inflammatory arthritis management. Patient Educ Couns. 2009; 75:334-9.
PubMed
CrossRef
 
Waalen J, Bruning AL, Peters MJ, Blau EM. A telephone-based intervention for increasing the use of osteoporosis medication: a randomized controlled trial. Am J Manag Care. 2009; 15:60-70.
PubMed
 
Solomon DH, Iversen MD, Avorn J, Gleeson T, Brookhart MA, Patrick AR, et al. Osteoporosis telephonic intervention to improve medication regimen adherence: a large, pragmatic, randomized controlled trial. Arch Intern Med. 2012; 172:477-83.
PubMed
 
Nietert PJ, Tilley BC, Zhao W, Edwards PF, Wessell AM, Mauldin PD, et al. Two pharmacy interventions to improve refill persistence for chronic disease medications: a randomized, controlled trial. Med Care. 2009; 47:32-40.
PubMed
CrossRef
 
Schnipper JL, Kirwin JL, Cotugno MC, Wahlstrom SA, Brown BA, Tarvin E, et al. Role of pharmacist counseling in preventing adverse drug events after hospitalization. Arch Intern Med. 2006; 166:565-71.
PubMed
CrossRef
 
Taylor CT, Byrd DC, Krueger K. Improving primary care in rural Alabama with a pharmacy initiative. Am J Health Syst Pharm. 2003; 60:1123-9.
PubMed
 
Sledge WH, Brown KE, Levine JM, Fiellin DA, Chawarski M, White WD, et al. A randomized trial of primary intensive care to reduce hospital admissions in patients with high utilization of inpatient services. Dis Manag. 2006; 9:328-38.
PubMed
CrossRef
 
Chernew ME, Shah MR, Wegh A, Rosenberg SN, Juster IA, Rosen AB, et al. Impact of decreasing copayments on medication adherence within a disease management environment. Health Aff (Millwood). 2008; 27:103-12.
PubMed
CrossRef
 
Choudhry NK, Fischer MA, Avorn J, Schneeweiss S, Solomon DH, Berman C, et al. At Pitney Bowes, value-based insurance design cut copayments and increased drug adherence. Health Aff (Millwood). 2010; 29:1995-2001.
PubMed
 
Maciejewski ML, Farley JF, Parker J, Wansink D. Copayment reductions generate greater medication adherence in targeted patients. Health Aff (Millwood). 2010; 29:2002-8.
PubMed
CrossRef
 
Choudhry NK, Avorn J, Glynn RJ, Antman EM, Schneeweiss S, Toscano M, et al, Post-Myocardial Infarction Free Rx Event and Economic Evaluation (MI FREEE) Trial. Full coverage for preventive medications after myocardial infarction. N Engl J Med. 2011; 365:2088-97.
PubMed
CrossRef
 
Zhang Y, Lave JR, Donohue JM, Fischer MA, Chernew ME, Newhouse JP. The impact of Medicare Part D on medication adherence among older adults enrolled in Medicare-Advantage products. Med Care. 2010; 48:409-17.
PubMed
CrossRef
 
Davidoff F, Batalden P, Stevens D, Ogrinc G, Mooney S, SQUIRE Development Group. Publication guidelines for quality improvement in health care: evolution of the SQUIRE project. Qual Saf Health Care. 2008; 17:Suppl 1i3-9.
PubMed
CrossRef
 

Figures

Grahic Jump Location
Appendix Figure.

Summary of evidence search and selection.

NA = not applicable; PICOTS = population, intervention, comparators, outcomes, timing, setting.

Grahic Jump Location

Tables

Table Jump PlaceholderAppendix Table 1. 

Inclusion and Exclusion Criteria

Table Jump PlaceholderAppendix Table 2. 

Definitions of Grades of Overall Strength of Evidence

Table Jump PlaceholderAppendix Table 3. 

Summary of Strength of Evidence, by Intervention Type

Table Jump PlaceholderAppendix Table 4. 

Summary of Evidence for Policy Interventions

References

Agency for Healthcare Research and Quality. Priority Areas for National Action: Transforming Health Care Quality. Rockville, MD: Agency for Healthcare Research and Quality; 2003.
 
Pathman DE, Konrad TR, Freed GL, Freeman VA, Koch GG. The awareness-to-adherence model of the steps to clinical guideline compliance. The case of pediatric vaccine recommendations. Med Care. 1996; 34:873-89.
PubMed
 
Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005; 353:487-97.
PubMed
CrossRef
 
World Health Organization. Noncommunicable Diseases and Mental Health: Progress Report 2002-2003. Geneva: World Health Organization; 2003.
 
Peterson AM, Takiya L, Finley R. Meta-analysis of trials of interventions to improve medication adherence. Am J Health Syst Pharm. 2003; 60:657-65.
PubMed
 
Haynes RB, Ackloo E, Sahota N, McDonald HP, Yao X. Interventions for enhancing medication adherence. Cochrane Database Syst Rev. 2008; CD000011.
PubMed
 
World Health Organization. The World Health Report 2002: Reducing Risks, Promoting Healthy Life. Geneva: World Health Organization; 2002.
 
World Health Organization. Adherence to Long-Term Therapies: Evidence for Action. Geneva: World Health Organization; 2003.
 
Dunbar-Jacob J, Erlen JA, Schlenk EA, Ryan CM, Sereika SM, Doswell WM. Adherence in chronic disease. Annu Rev Nurs Res. 2000; 18:48-90.
PubMed
 
Sarquis LM, Dellácqua MC, Gallani MC, Moreira RM, Bocchi SC, Tase TH, et al. [Compliance in antihypertensive therapy: analyses in scientific articles]. Rev Esc Enferm USP. 1998; 32:335-53.
PubMed
 
DiMatteo MR, Giordani PJ, Lepper HS, Croghan TW. Patient adherence and medical treatment outcomes: a meta-analysis. Med Care. 2002; 40:794-811.
PubMed
 
Schiff GD, Fung S, Speroff T, McNutt RA. Decompensated heart failure: symptoms, patterns of onset, and contributing factors. Am J Med. 2003; 114:625-30.
PubMed
CrossRef
 
Waeber B, Burnier M, Brunner HR. How to improve adherence with prescribed treatment in hypertensive patients? J Cardiovasc Pharmacol. 2000; 35:Suppl 3S23-6.
PubMed
CrossRef
 
Psaty BM, Koepsell TD, Wagner EH, LoGerfo JP, Inui TS. The relative risk of incident coronary heart disease associated with recently stopping the use of beta-blockers. JAMA. 1990; 263:1653-7.
PubMed
CrossRef
 
Beckles GL, Engelgau MM, Narayan KM, Herman WH, Aubert RE, Williamson DF. Population-based assessment of the level of care among adults with diabetes in the U.S. Diabetes Care. 1998; 21:1432-8.
PubMed
CrossRef
 
Rogers PG, Bullman W. Prescription medicine compliance: review of the baseline of knowledge—report of the National Council on Patient Information and Education. Journal of Pharmacoepidemiology. 1995; 3:3-36.
 
Mahoney JJ, Ansell BJ, Fleming WK, Butterworth SW. The unhidden cost of noncompliance. J Manag Care Pharm. 2008; 14:S1-S29.
 
New England Healthcare Institute. Thinking Outside the Pillbox: A System-wide Approach to Improving Patient Medication Adherence for Chronic Disease. Cambridge, MA: New England Healthcare Institute; 2009.
 
Showalter A. Costs of Patient Noncompliance. Crystal Lake, IL: AlignMap; 2006; 1-4.
 
Task Force for Compliance. Noncompliance with Medications: An Economic Tragedy with Important Implications for Health Care Reform. Washington, DC: Task Force for Compliance; 1994.
 
Shojania KG, McDonald KM, Wachter R, Owens DK. Closing the Quality Gap: A Critical Analysis of Quality Improvement Strategies: Volume 1—Series Overview and Methodology. AHRQ publication no. 04-0051-1. (Prepared by the Stanford University-UCSF Evidence-based Practice Center under contract 290-02-0017.). Rockville, MD: Agency for Healthcare Research and Quality; 2004.
 
Simoni JM, Pearson CR, Pantalone DW, Marks G, Crepaz N. Efficacy of interventions in improving highly active antiretroviral therapy adherence and HIV-1 RNA viral load. A meta-analytic review of randomized controlled trials. J Acquir Immune Defic Syndr. 2006; 43:Suppl 1S23-35.
PubMed
CrossRef
 
Rueda S, Park-Wyllie LY, Bayoumi AM, Tynan AM, Antoniou TA, Rourke SB, et al. Patient support and education for promoting adherence to highly active antiretroviral therapy for HIV/AIDS. Cochrane Database Syst Rev. 2006; CD001442.
PubMed
 
Roter DL, Hall JA, Merisca R, Nordstrom B, Cretin D, Svarstad B. Effectiveness of interventions to improve patient compliance: a meta-analysis. Med Care. 1998; 36:1138-61.
PubMed
CrossRef
 
Gellad WF, Grenard JL, Marcum ZA. A systematic review of barriers to medication adherence in the elderly: looking beyond cost and regimen complexity. Am J Geriatr Pharmacother. 2011; 9:11-23.
PubMed
CrossRef
 
Grenard JL, Munjas BA, Adams JL, Suttorp M, Maglione M, McGlynn EA, et al. Depression and medication adherence in the treatment of chronic diseases in the United States: a meta-analysis. J Gen Intern Med. 2011; 26:1175-82.
PubMed
CrossRef
 
Briesacher BA, Gurwitz JH, Soumerai SB. Patients at-risk for cost-related medication nonadherence: a review of the literature. J Gen Intern Med. 2007; 22:864-71.
PubMed
CrossRef
 
Kennedy J, Morgan S. A cross-national study of prescription nonadherence due to cost: data from the Joint Canada-United States Survey of Health. Clin Ther. 2006; 28:1217-24.
PubMed
CrossRef
 
Kennedy J, Morgan S. Cost-related prescription nonadherence in the United States and Canada: a system-level comparison using the 2007 International Health Policy Survey in Seven Countries. Clin Ther. 2009; 31:213-9.
PubMed
 
Bocchi EA, Cruz F, Guimarães G, Pinho Moreira LF, Issa VS, Ayub Ferreira SM, et al. Long-term prospective, randomized, controlled study using repetitive education at six-month intervals and monitoring for adherence in heart failure outpatients: the REMADHE trial. Circ Heart Fail. 2008; 1:115-24.
PubMed
CrossRef
 
de Castro MS, Fuchs FD, Santos MC, Maximiliano P, Gus M, Moreira LB, et al. Pharmaceutical care program for patients with uncontrolled hypertension. Report of a double-blind clinical trial with ambulatory blood pressure monitoring. Am J Hypertens. 2006; 19:528-33.
PubMed
 
Ponnusankar S, Surulivelrajan M, Anandamoorthy N, Suresh B. Assessment of impact of medication counseling on patients' medication knowledge and compliance in an outpatient clinic in South India. Patient Educ Couns. 2004; 54:55-60.
PubMed
CrossRef
 
Seck BC, Jackson RT. Determinants of compliance with iron supplementation among pregnant women in Senegal. Public Health Nutr. 2008; 11:596-605.
PubMed
CrossRef
 
Stewart A, Noakes T, Eales C, Shepard K, Becker P, Veriawa Y. Adherence to cardiovascular risk factor modification in patients with hypertension. Cardiovasc J S Afr. 2005; 16:102-7.
PubMed
 
Phumipamorn S, Pongwecharak J, Soorapan S, Pattharachayakul S. Effects of the pharmacist's input on glycaemic control and cardiovascular risks in Muslim diabetes. Prim Care Diabetes. 2008; 2:31-7.
PubMed
CrossRef
 
Sookaneknun P, Richards RM, Sanguansermsri J, Teerasut C. Pharmacist involvement in primary care improves hypertensive patient clinical outcomes. Ann Pharmacother. 2004; 38:2023-8.
PubMed
CrossRef
 
Delmas PD, Vrijens B, Eastell R, Roux C, Pols HA, Ringe JD, et al, Improving Measurements of Persistence on Actonel Treatment (IMPACT) Investigators. Effect of monitoring bone turnover markers on persistence with risedronate treatment of postmenopausal osteoporosis. J Clin Endocrinol Metab. 2007; 92:1296-304.
PubMed
CrossRef
 
Sovani MP, Whale CI, Oborne J, Cooper S, Mortimer K, Ekström T, et al. Poor adherence with inhaled corticosteroids for asthma: can using a single inhaler containing budesonide and formoterol help? Br J Gen Pract. 2008; 58:37-43.
PubMed
CrossRef
 
Perahia DG, Quail D, Gandhi P, Walker DJ, Peveler RC. A randomized, controlled trial of duloxetine alone vs. duloxetine plus a telephone intervention in the treatment of depression. J Affect Disord. 2008; 108:33-41.
PubMed
CrossRef
 
Atherton-Naji A, Hamilton R, Riddle W, Naji S. Improving adherence to antidepressant drug treatment in primary care: a feasibility study for a randomized controlled trial of educational intervention. Primary Care Psychiatry. 2001; 7:61-7.
CrossRef
 
Claxton A, de Klerk E, Parry M, Robinson JM, Schmidt ME. Patient compliance to a new enteric-coated weekly formulation of fluoxetine during continuation treatment of major depressive disorder. J Clin Psychiatry. 2000; 61:928-32.
PubMed
CrossRef
 
Peveler R, George C, Kinmonth AL, Campbell M, Thompson C. Effect of antidepressant drug counselling and information leaflets on adherence to drug treatment in primary care: randomised controlled trial. BMJ. 1999; 319:612-5.
PubMed
CrossRef
 
Nazareth I, Burton A, Shulman S, Smith P, Haines A, Timberal H. A pharmacy discharge plan for hospitalized elderly patients—a randomized controlled trial. Age Ageing. 2001; 30:33-40.
PubMed
CrossRef
 
Begley S, Livingstone C, Hodges N, Williamson V. Impact of domiciliary pharmacy visits on medication management in an elderly population. Int J Pharm Pract. 1997; 5:111-21.
CrossRef
 
Brown I, Sheeran P, Reuber M. Enhancing antiepileptic drug adherence: a randomized controlled trial. Epilepsy Behav. 2009; 16:634-9.
PubMed
CrossRef
 
Goodyer LI, Miskelly F, Milligan P. Does encouraging good compliance improve patients' clinical condition in heart failure? Br J Clin Pract. 1995; 49:173-6.
PubMed
 
Cooper A, Drake J, Brankin E, PERSIST Investigators. Treatment persistence with once-monthly ibandronate and patient support vs. once-weekly alendronate: results from the PERSIST study. Int J Clin Pract. 2006; 60:896-905.
PubMed
CrossRef
 
Clowes JA, Peel NF, Eastell R. The impact of monitoring on adherence and persistence with antiresorptive treatment for postmenopausal osteoporosis: a randomized controlled trial. J Clin Endocrinol Metab. 2004; 89:1117-23.
PubMed
CrossRef
 
Grosset KA, Grosset DG. Effect of educational intervention on medication timing in Parkinson's disease: a randomized controlled trial. BMC Neurol. 2007; 7:20.
PubMed
CrossRef
 
Hardstaff R, Green K, Talbot D. Measurement of compliance posttransplantation—the results of a 12-month study using electronic monitoring. Transplant Proc. 2003; 35:796-7.
PubMed
CrossRef
 
Homer D, Nightingale P, Jobanputra P. Providing patients with information about disease-modifying anti-rheumatic drugs: Individually or in groups? A pilot randomized controlled trial comparing adherence and satisfaction. Musculoskeletal Care. 2009; 7:78-92.
PubMed
CrossRef
 
Hill J, Bird H, Johnson S. Effect of patient education on adherence to drug treatment for rheumatoid arthritis: a randomised controlled trial. Ann Rheum Dis. 2001; 60:869-75.
PubMed
 
Sturgess IK, McElnay JC, Hughes CM, Crealey G. Community pharmacy based provision of pharmaceutical care to older patients. Pharm World Sci. 2003; 25:218-26.
PubMed
CrossRef
 
Varma S, McElnay JC, Hughes CM, Passmore AP, Varma M. Pharmaceutical care of patients with congestive heart failure: interventions and outcomes. Pharmacotherapy. 1999; 19:860-9.
PubMed
CrossRef
 
Coté J, Cartier A, Robichaud P, Boutin H, Malo JL, Rouleau M, et al. Influence on asthma morbidity of asthma education programs based on self-management plans following treatment optimization. Am J Respir Crit Care Med. 1997; 155:1509-14.
PubMed
 
Côté J, Bowie DM, Robichaud P, Parent JG, Battisti L, Boulet LP. Evaluation of two different educational interventions for adult patients consulting with an acute asthma exacerbation. Am J Respir Crit Care Med. 2001; 163:1415-9.
PubMed
 
Tamblyn R, Reidel K, Huang A, Taylor L, Winslade N, Bartlett G, et al. Increasing the detection and response to adherence problems with cardiovascular medication in primary care through computerized drug management systems: a randomized controlled trial. Med Decis Making. 2010; 30:176-88.
PubMed
CrossRef
 
Gwadry-Sridhar FH, Arnold JM, Zhang Y, Brown JE, Marchiori G, Guyatt G. Pilot study to determine the impact of a multidisciplinary educational intervention in patients hospitalized with heart failure. Am Heart J. 2005; 150:982.
PubMed
CrossRef
 
Tsuyuki RT, Fradette M, Johnson JA, Bungard TJ, Eurich DT, Ashton T, et al. A multicenter disease management program for hospitalized patients with heart failure. J Card Fail. 2004; 10:473-80.
PubMed
CrossRef
 
Rinfret S, Lussier MT, Peirce A, Duhamel F, Cossette S, Lalonde L, et al, LOYAL Study Investigators. The impact of a multidisciplinary information technology-supported program on blood pressure control in primary care. Circ Cardiovasc Qual Outcomes. 2009; 2:170-7.
PubMed
CrossRef
 
Edworthy SM, Baptie B, Galvin D, Brant RF, Churchill-Smith T, Manyari D, et al. Effects of an enhanced secondary prevention program for patients with heart disease: a prospective randomized trial. Can J Cardiol. 2007; 23:1066-72.
PubMed
CrossRef
 
Leenen FH, Wilson TW, Bolli P, Larochelle P, Myers M, Handa SP, et al. Patterns of compliance with once versus twice daily antihypertensive drug therapy in primary care: a randomized clinical trial using electronic monitoring. Can J Cardiol. 1997; 13:914-20.
PubMed
 
Waters BM, Jensen L, Fedorak RN. Effects of formal education for patients with inflammatory bowel disease: a randomized controlled trial. Can J Gastroenterol. 2005; 19:235-44.
PubMed
 
Sherrard H, Struthers C, Kearns SA, Wells G, Chen L, Mesana T. Using technology to create a medication safety net for cardiac surgery patients: a nurse-led randomized control trial. Can J Cardiovasc Nurs. 2009; 19:9-15.
PubMed
 
Peterson GM, Fitzmaurice KD, Naunton M, Vial JH, Stewart K, Krum H. Impact of pharmacist-conducted home visits on the outcomes of lipid-lowering drug therapy. J Clin Pharm Ther. 2004; 29:23-30.
PubMed
CrossRef
 
Vrijens B, Goetghebeur E. Comparing compliance patterns between randomized treatments. Control Clin Trials. 1997; 18:187-203.
PubMed
CrossRef
 
Rubak S, Sandbæk A, Lauritzen T, Borch-Johnsen K, Christensen B. Effect of “motivational interviewing” on quality of care measures in screen detected type 2 diabetes patients: a one-year follow-up of an RCT, ADDITION Denmark. Scand J Prim Health Care. 2011; 29:92-8.
PubMed
CrossRef
 
Christensen A, Christrup LL, Fabricius PE, Chrostowska M, Wronka M, Narkiewicz K, et al. The impact of an electronic monitoring and reminder device on patient compliance with antihypertensive therapy: a randomized controlled trial. J Hypertens. 2010; 28:194-200.
PubMed
CrossRef
 
Hornnes N, Larsen K, Boysen G. Blood pressure 1 year after stroke: the need to optimize secondary prevention. J Stroke Cerebrovasc Dis. 2011; 20:16-23.
PubMed
CrossRef
 
Nielsen D, Ryg J, Nielsen W, Knold B, Nissen N, Brixen K. Patient education in groups increases knowledge of osteoporosis and adherence to treatment: a two-year randomized controlled trial. Patient Educ Couns. 2010; 81:155-60.
PubMed
CrossRef
 
Brus HL, van de Laar MA, Taal E, Rasker JJ, Wiegman O. Effects of patient education on compliance with basic treatment regimens and health in recent onset active rheumatoid arthritis. Ann Rheum Dis. 1998; 57:146-51.
PubMed
CrossRef
 
Elkjaer M, Shuhaibar M, Burisch J, Bailey Y, Scherfig H, Laugesen B, et al. E-health empowers patients with ulcerative colitis: a randomised controlled trial of the web-guided ‘Constant-care’ approach. Gut. 2010; 59:1652-61.
PubMed
CrossRef
 
Billault B, Degoulet P, Devries C, Plouin PF, Chatellier G, Menard J. Use of a standardized personal medical record by patients with hypertension: a randomized controlled prospective trial. MD Comput. 1995; 12:31-5.
PubMed
 
Andrejak M, Genes N, Vaur L, Poncelet P, Clerson P, Carré A. Electronic pill-boxes in the evaluation of antihypertensive treatment compliance: comparison of once daily versus twice daily regimen. Am J Hypertens. 2000; 13:184-90.
PubMed
CrossRef
 
Boissel JP, Meillard O, Perrin-Fayolle E, Ducruet T, Alamercery Y, Sassano P, et al. Comparison between a bid and a tid regimen: improved compliance with no improved antihypertensive effect. The EOL Research Group. Eur J Clin Pharmacol. 1996; 50:63-7.
PubMed
CrossRef
 
Gensichen J, von Korff M, Peitz M, Muth C, Beyer M, Güthlin C, et al, PRoMPT (PRimary care Monitoring for depressive Patients Trial). Case management for depression by health care assistants in small primary care practices: a cluster randomized trial. Ann Intern Med. 2009; 151:369-78.
PubMed
CrossRef
 
Mengden T, Vetter H, Tousset E, Uen S. Management of patients with uncontrolled arterial hypertension—the role of electronic compliance monitoring, 24-h ambulatory blood pressure monitoring and Candesartan/HCTZ. BMC Cardiovasc Disord. 2006; 6:36.
PubMed
CrossRef
 
Klein A, Otto G, Krämer I. Impact of a pharmaceutical care program on liver transplant patients' compliance with immunosuppressive medication: a prospective, randomized, controlled trial using electronic monitoring. Transplantation. 2009; 87:839-47.
PubMed
CrossRef
 
Wong FK, Chow SK, Chan TM. Evaluation of a nurse-led disease management programme for chronic kidney disease: a randomized controlled trial. Int J Nurs Stud. 2010; 47:268-78.
PubMed
 
Wu JY, Leung WY, Chang S, Lee B, Zee B, Tong PC, et al. Effectiveness of telephone counselling by a pharmacist in reducing mortality in patients receiving polypharmacy: randomised controlled trial. BMJ. 2006; 333:522.
PubMed
CrossRef
 
Vergouwen AC, Bakker A, Burger H, Verheij TJ, Koerselman F. A cluster randomized trial comparing two interventions to improve treatment of major depression in primary care. Psychol Med. 2005; 35:25-33.
PubMed
CrossRef
 
Eussen SR, van der Elst ME, Klungel OH, Rompelberg CJ, Garssen J, Oosterveld MH, et al. A pharmaceutical care program to improve adherence to statin therapy: a randomized controlled trial. Ann Pharmacother. 2010; 44:1905-13.
PubMed
CrossRef
 
Charles T, Quinn D, Weatherall M, Aldington S, Beasley R, Holt S. An audiovisual reminder function improves adherence with inhaled corticosteroid therapy in asthma. J Allergy Clin Immunol. 2007; 119:811-6.
PubMed
CrossRef
 
Gallefoss F, Bakke PS. How does patient education and self-management among asthmatics and patients with chronic obstructive pulmonary disease affect medication? Am J Respir Crit Care Med. 1999; 160:2000-5.
PubMed
CrossRef
 
López-Viña A, del Castillo-Arévalo E. Influence of peak expiratory flow monitoring on an asthma self-management education programme. Respir Med. 2000; 94:760-6.
PubMed
CrossRef
 
López Cabezas C, Falces Salvador C, Cubí Quadrada D, Arnau Bartés A, Ylla Boré M, Muro Perea N, et al. Randomized clinical trial of a postdischarge pharmaceutical care program vs regular follow-up in patients with heart failure. Farm Hosp. 2006; 30:328-42.
PubMed
CrossRef
 
Pladevall M, Brotons C, Gabriel R, Arnau A, Suarez C, de la Figuera M, et al, Writing Committee on behalf of the COM99 Study Group. Multicenter cluster-randomized trial of a multifactorial intervention to improve antihypertensive medication adherence and blood pressure control among patients at high cardiovascular risk (the COM99 study). Circulation. 2010; 122:1183-91.
PubMed
CrossRef
 
Amado Guirado E, Pujol Ribera E, Pacheco Huergo V, Borras JM, ADIEHTA Group. Knowledge and adherence to antihypertensive therapy in primary care: results of a randomized trial. Gac Sanit. 2011; 25:62-7.
PubMed
CrossRef
 
Akerblad AC, Bengtsson F, Ekselius L, von Knorring L. Effects of an educational compliance enhancement programme and therapeutic drug monitoring on treatment adherence in depressed patients managed by general practitioners. Int Clin Psychopharmacol. 2003; 18:347-54.
PubMed
 
Chen SY, Sheu S, Chang CS, Wang TH, Huang MS. The effects of the self-efficacy method on adult asthmatic patient self-care behavior. J Nurs Res. 2010; 18:266-74.
PubMed
 
Norris SL, Atkins D, Bruening W, Fox S, Johnson E, Kane R, et al. Observational studies in systemic reviews of comparative effectiveness: AHRQ and the Effective Health Care Program. J Clin Epidemiol. 2011; 64:1178-86.
PubMed
 
Agency for Healthcare Research and Quality. Methods Guide for Effectiveness and Comparative Effectiveness Reviews. Rockville, MD: Agency for Healthcare Research and Quality; 2011.
 
Viswanathan M, Berkman ND. Development of the RTI item bank on risk of bias and precision of observational studies. J Clin Epidemiol. 2012; 65:163-78.
PubMed
CrossRef
 
Owens DK, Lohr KN, Atkins D, Treadwell JR, Reston JT, Bass EB, et al. AHRQ series paper 5: grading the strength of a body of evidence when comparing medical interventions—Agency for Healthcare Research and Quality and the Effective Health-Care Program. J Clin Epidemiol. 2010; 63:513-23.
PubMed
CrossRef
 
Bogner HR, de Vries HF. Integrating type 2 diabetes mellitus and depression treatment among African Americans: a randomized controlled pilot trial. Diabetes Educ. 2010; 36:284-92.
PubMed
CrossRef
 
Bogner HR, Morales KH, de Vries HF, Cappola AR. Integrated management of type 2 diabetes mellitus and depression treatment to improve medication adherence: a randomized controlled trial. Ann Fam Med. 2012; 10:15-22.
PubMed
CrossRef
 
Lin EH, Katon W, Rutter C, Simon GE, Ludman EJ, Von Korff M, et al. Effects of enhanced depression treatment on diabetes self-care. Ann Fam Med. 2006; 4:46-53.
PubMed
CrossRef
 
Pearce KA, Love MM, Shelton BJ, Schoenberg NE, Williamson MA, Barron MA, et al, Kentucky Ambulatory Network. Cardiovascular risk education and social support (CaRESS): report of a randomized controlled trial from the Kentucky Ambulatory Network (KAN). J Am Board Fam Med. 2008; 21:269-81.
PubMed
CrossRef
 
Wolever RQ, Dreusicke M, Fikkan J, Hawkins TV, Yeung S, Wakefield J, et al. Integrative health coaching for patients with type 2 diabetes: a randomized clinical trial. Diabetes Educ. 2010; 36:629-39.
PubMed
CrossRef
 
Grant RW, Devita NG, Singer DE, Meigs JB. Improving adherence and reducing medication discrepancies in patients with diabetes. Ann Pharmacother. 2003; 37:962-9.
PubMed
CrossRef
 
Mann DM, Ponieman D, Montori VM, Arciniega J, McGinn T. The Statin Choice decision aid in primary care: a randomized trial. Patient Educ Couns. 2010; 80:138-40.
PubMed
CrossRef
 
Weymiller AJ, Montori VM, Jones LA, Gafni A, Guyatt GH, Bryant SC, et al. Helping patients with type 2 diabetes mellitus make treatment decisions: statin choice randomized trial. Arch Intern Med. 2007; 167:1076-82.
PubMed
CrossRef
 
Jones LA, Weymiller AJ, Shah N, Bryant SC, Christianson TJ, Guyatt GH, et al. Should clinicians deliver decision aids? Further exploration of the statin choice randomized trial results. Med Decis Making. 2009; 29:468-74.
PubMed
CrossRef
 
Guthrie RM. The effects of postal and telephone reminders on compliance with pravastatin therapy in a national registry: results of the first myocardial infarction risk reduction program. Clin Ther. 2001; 23:970-80.
PubMed
CrossRef
 
Johnson SS, Driskell MM, Johnson JL, Dyment SJ, Prochaska JO, Prochaska JM, et al. Transtheoretical model intervention for adherence to lipid-lowering drugs. Dis Manag. 2006; 9:102-14.
PubMed
 
Powell KM, Edgren B. Failure of educational videotapes to improve medication compliance in a health maintenance organization. Am J Health Syst Pharm. 1995; 52:2196-9.
PubMed
 
Schectman G, Hiatt J, Hartz A. Telephone contacts do not improve adherence to niacin or bile acid sequestrant therapy. Ann Pharmacother. 1994; 28:29-35.
PubMed
 
Stacy JN, Schwartz SM, Ershoff D, Shreve MS. Incorporating tailored interactive patient solutions using interactive voice response technology to improve statin adherence: results of a randomized clinical trial in a managed care setting. Popul Health Manag. 2009; 12:241-54.
PubMed
CrossRef
 
Lee JK, Grace KA, Taylor AJ. Effect of a pharmacy care program on medication adherence and persistence, blood pressure, and low-density lipoprotein cholesterol: a randomized controlled trial. JAMA. 2006; 296:2563-71.
PubMed
 
Schneider PJ, Murphy JE, Pedersen CA. Impact of medication packaging on adherence and treatment outcomes in older ambulatory patients. J Am Pharm Assoc (2003). 2008; 48:58-63.
PubMed
 
Bogner HR, de Vries HF. Integration of depression and hypertension treatment: a pilot, randomized controlled trial. Ann Fam Med. 2008; 6:295-301.
PubMed
CrossRef
 
Rudd P, Miller NH, Kaufman J, Kraemer HC, Bandura A, Greenwald G, et al. Nurse management for hypertension. A systems approach. Am J Hypertens. 2004; 17:921-7.
PubMed
 
Wakefield BJ, Holman JE, Ray A, Scherubel M, Adams MR, Hillis SL, et al. Effectiveness of home telehealth in comorbid diabetes and hypertension: a randomized, controlled trial. Telemed J E Health. 2011; 17:254-61.
PubMed
CrossRef
 
Carter BL, Ardery G, Dawson JD, James PA, Bergus GR, Doucette WR, et al. Physician and pharmacist collaboration to improve blood pressure control. Arch Intern Med. 2009; 169:1996-2002.
PubMed
CrossRef
 
Hunt JS, Siemienczuk J, Pape G, Rozenfeld Y, MacKay J, LeBlanc BH, et al. A randomized controlled trial of team-based care: impact of physician-pharmacist collaboration on uncontrolled hypertension. J Gen Intern Med. 2008; 23:1966-72.
PubMed
CrossRef
 
Solomon DK, Portner TS, Bass GE, Gourley DR, Gourley GA, Holt JM, et al. Clinical and economic outcomes in the hypertension and COPD arms of a multicenter outcomes study. J Am Pharm Assoc (Wash). 1998; 38:574-85.
PubMed
 
Gourley GA, Portner TS, Gourley DR, Rigolosi EL, Holt JM, Solomon DK, et al. Humanistic outcomes in the hypertension and COPD arms of a multicenter outcomes study. J Am Pharm Assoc (Wash). 1998; 38:586-97.
PubMed
 
Vivian EM. Improving blood pressure control in a pharmacist-managed hypertension clinic. Pharmacotherapy. 2002; 22:1533-40.
PubMed
CrossRef
 
Bosworth HB, Olsen MK, Neary A, Orr M, Grubber J, Svetkey L, et al. Take Control of Your Blood Pressure (TCYB) study: a multifactorial tailored behavioral and educational intervention for achieving blood pressure control. Patient Educ Couns. 2008; 70:338-47.
PubMed
CrossRef
 
Bosworth HB, Olsen MK, Dudley T, Orr M, Neary A, Harrelson M, et al. The Take Control of Your Blood Pressure (TCYB) study: study design and methodology. Contemp Clin Trials. 2007; 28:33-47.
PubMed
CrossRef
 
Bosworth HB, Olsen MK, Gentry P, Orr M, Dudley T, McCant F, et al. Nurse administered telephone intervention for blood pressure control: a patient-tailored multifactorial intervention. Patient Educ Couns. 2005; 57:5-14.
PubMed
CrossRef
 
Friedman RH, Kazis LE, Jette A, Smith MB, Stollerman J, Torgerson J, et al. A telecommunications system for monitoring and counseling patients with hypertension. Impact on medication adherence and blood pressure control. Am J Hypertens. 1996; 9:285-92.
PubMed
CrossRef
 
Johnson SS, Driskell MM, Johnson JL, Prochaska JM, Zwick W, Prochaska JO. Efficacy of a transtheoretical model-based expert system for antihypertensive adherence. Dis Manag. 2006; 9:291-301.
PubMed
 
Ogedegbe GO, Boutin-Foster C, Wells MT, Allegrante JP, Isen AM, Jobe JB, et al. A randomized controlled trial of positive-affect intervention and medication adherence in hypertensive African Americans. Arch Intern Med. 2012; 172:322-6.
PubMed
CrossRef
 
Powers BJ, Danus S, Grubber JM, Olsen MK, Oddone EZ, Bosworth HB. The effectiveness of personalized coronary heart disease and stroke risk communication. Am Heart J. 2011; 161:673-80.
PubMed
CrossRef
 
Ross SE, Moore LA, Earnest MA, Wittevrongel L, Lin CT. Providing a web-based online medical record with electronic communication capabilities to patients with congestive heart failure: randomized trial. J Med Internet Res. 2004; 6:12.
PubMed
CrossRef
 
Rich MW, Gray DB, Beckham V, Wittenberg C, Luther P. Effect of a multidisciplinary intervention on medication compliance in elderly patients with congestive heart failure. Am J Med. 1996; 101:270-6.
PubMed
CrossRef
 
Wu JR, Corley DJ, Lennie TA, Moser DK. Effect of a medication-taking behavior feedback theory-based intervention on outcomes in patients with heart failure. J Card Fail. 2012; 18:1-9.
PubMed
CrossRef
 
Murray MD, Young J, Hoke S, Tu W, Weiner M, Morrow D, et al. Pharmacist intervention to improve medication adherence in heart failure: a randomized trial. Ann Intern Med. 2007; 146:714-25.
PubMed
CrossRef
 
Fulmer TT, Feldman PH, Kim TS, Carty B, Beers M, Molina M, et al. An intervention study to enhance medication compliance in community-dwelling elderly individuals. J Gerontol Nurs. 1999; 25:6-14.
PubMed
 
Smith DH, Kramer JM, Perrin N, Platt R, Roblin DW, Lane K, et al.  A randomized trial of direct-to-patient communication to enhance adherence to beta-blocker therapy following myocardial infarction. Arch Intern Med. 2008;168:477-83; discussion 483; quiz 447. [PMID: 18332291]
 
Bender BG, Apter A, Bogen DK, Dickinson P, Fisher L, Wamboldt FS, et al. Test of an interactive voice response intervention to improve adherence to controller medications in adults with asthma. J Am Board Fam Med. 2010; 23:159-65.
PubMed
CrossRef
 
Berg J, Dunbar-Jacob J, Sereika SM. An evaluation of a self-management program for adults with asthma. Clin Nurs Res. 1997; 6:225-38.
PubMed
CrossRef
 
Janson SL, Fahy JV, Covington JK, Paul SM, Gold WM, Boushey HA. Effects of individual self-management education on clinical, biological, and adherence outcomes in asthma. Am J Med. 2003; 115:620-6.
PubMed
CrossRef
 
Janson SL, McGrath KW, Covington JK, Cheng SC, Boushey HA. Individualized asthma self-management improves medication adherence and markers of asthma control. J Allergy Clin Immunol. 2009; 123:840-6.
PubMed
CrossRef
 
Schaffer SD, Tian L. Promoting adherence: effects of theory-based asthma education. Clin Nurs Res. 2004; 13:69-89.
PubMed
CrossRef
 
Wilson SR, Strub P, Buist AS, Knowles SB, Lavori PW, Lapidus J, et al, Better Outcomes of Asthma Treatment (BOAT) Study Group. Shared treatment decision making improves adherence and outcomes in poorly controlled asthma. Am J Respir Crit Care Med. 2010; 181:566-77.
PubMed
CrossRef
 
Williams LK, Peterson EL, Wells K, Campbell J, Wang M, Chowdhry VK, et al. A cluster-randomized trial to provide clinicians inhaled corticosteroid adherence information for their patients with asthma. J Allergy Clin Immunol. 2010; 126:225-31, 231.e1-4.
PubMed
CrossRef
 
Weinberger M, Murray MD, Marrero DG, Brewer N, Lykens M, Harris LE, et al. Effectiveness of pharmacist care for patients with reactive airways disease: a randomized controlled trial. JAMA. 2002; 288:1594-602.
PubMed
CrossRef
 
Katon W, Rutter C, Ludman EJ, Von Korff M, Lin E, Simon G, et al. A randomized trial of relapse prevention of depression in primary care. Arch Gen Psychiatry. 2001; 58:241-7.
PubMed
CrossRef
 
Ludman E, Katon W, Bush T, Rutter C, Lin E, Simon G, et al. Behavioural factors associated with symptom outcomes in a primary care-based depression prevention intervention trial. Psychol Med. 2003; 33:1061-70.
PubMed
CrossRef
 
Von Korff M, Katon W, Rutter C, Ludman E, Simon G, Lin E, et al. Effect on disability outcomes of a depression relapse prevention program. Psychosom Med. 2003; 65:938-43.
PubMed
CrossRef
 
Capoccia KL, Boudreau DM, Blough DK, Ellsworth AJ, Clark DR, Stevens NG, et al. Randomized trial of pharmacist interventions to improve depression care and outcomes in primary care. Am J Health Syst Pharm. 2004; 61:364-72.
PubMed
 
Katon W, Von Korff M, Lin E, Walker E, Simon GE, Bush T, et al. Collaborative management to achieve treatment guidelines. Impact on depression in primary care. JAMA. 1995; 273:1026-31.
PubMed
CrossRef
 
Katon W, Robinson P, Von Korff M, Lin E, Bush T, Ludman E, et al. A multifaceted intervention to improve treatment of depression in primary care. Arch Gen Psychiatry. 1996; 53:924-32.
PubMed
CrossRef
 
Katon W, Von Korff M, Lin E, Simon G, Walker E, Unützer J, et al. Stepped collaborative care for primary care patients with persistent symptoms of depression: a randomized trial. Arch Gen Psychiatry. 1999; 56:1109-15.
PubMed
CrossRef
 
Katon W, Russo J, Von Korff M, Lin E, Simon G, Bush T, et al. Long-term effects of a collaborative care intervention in persistently depressed primary care patients. J Gen Intern Med. 2002; 17:741-8.
PubMed
CrossRef
 
Pyne JM, Fortney JC, Curran GM, Tripathi S, Atkinson JH, Kilbourne AM, et al. Effectiveness of collaborative care for depression in human immunodeficiency virus clinics. Arch Intern Med. 2011; 171:23-31.
PubMed
 
Rickles NM, Svarstad BL, Statz-Paynter JL, Taylor LV, Kobak KA. Pharmacist telemonitoring of antidepressant use: effects on pharmacist-patient collaboration. J Am Pharm Assoc (2003). 2005; 45:344-53.
PubMed
 
Simon GE, Ludman EJ, Operskalski BH. Randomized trial of a telephone care management program for outpatients starting antidepressant treatment. Psychiatr Serv. 2006; 57:1441-5.
PubMed
CrossRef
 
Simon GE, Ludman EJ, Tutty S, Operskalski B, Von Korff M. Telephone psychotherapy and telephone care management for primary care patients starting antidepressant treatment: a randomized controlled trial. JAMA. 2004; 292:935-42.
PubMed
 
Hoffman L, Enders J, Luo J, Segal R, Pippins J, Kimberlin C. Impact of an antidepressant management program on medication adherence. Am J Manag Care. 2003; 9:70-80.
PubMed
 
Okeke CO, Quigley HA, Jampel HD, Ying GS, Plyler RJ, Jiang Y, et al. Interventions improve poor adherence with once daily glaucoma medications in electronically monitored patients. Ophthalmology. 2009; 116:2286-93.
PubMed
 
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; 45:466-72.
PubMed
 
Montori VM, Shah ND, Pencille LJ, Branda ME, VanHouten HK, Swiglo BA, et al. Use of a decision aid to improve treatment decisions in osteoporosis: the osteoporosis choice randomized trial. Am J Med. 2011; 124:549-56.
PubMed
CrossRef
 
Rudd RE, Blanch DC, Gall V, Chibnik LB, Wright EA, Reichmann W, et al. A randomized controlled trial of an intervention to reduce low literacy barriers in inflammatory arthritis management. Patient Educ Couns. 2009; 75:334-9.
PubMed
CrossRef
 
Waalen J, Bruning AL, Peters MJ, Blau EM. A telephone-based intervention for increasing the use of osteoporosis medication: a randomized controlled trial. Am J Manag Care. 2009; 15:60-70.
PubMed
 
Solomon DH, Iversen MD, Avorn J, Gleeson T, Brookhart MA, Patrick AR, et al. Osteoporosis telephonic intervention to improve medication regimen adherence: a large, pragmatic, randomized controlled trial. Arch Intern Med. 2012; 172:477-83.
PubMed
 
Nietert PJ, Tilley BC, Zhao W, Edwards PF, Wessell AM, Mauldin PD, et al. Two pharmacy interventions to improve refill persistence for chronic disease medications: a randomized, controlled trial. Med Care. 2009; 47:32-40.
PubMed
CrossRef
 
Schnipper JL, Kirwin JL, Cotugno MC, Wahlstrom SA, Brown BA, Tarvin E, et al. Role of pharmacist counseling in preventing adverse drug events after hospitalization. Arch Intern Med. 2006; 166:565-71.
PubMed
CrossRef
 
Taylor CT, Byrd DC, Krueger K. Improving primary care in rural Alabama with a pharmacy initiative. Am J Health Syst Pharm. 2003; 60:1123-9.
PubMed
 
Sledge WH, Brown KE, Levine JM, Fiellin DA, Chawarski M, White WD, et al. A randomized trial of primary intensive care to reduce hospital admissions in patients with high utilization of inpatient services. Dis Manag. 2006; 9:328-38.
PubMed
CrossRef
 
Chernew ME, Shah MR, Wegh A, Rosenberg SN, Juster IA, Rosen AB, et al. Impact of decreasing copayments on medication adherence within a disease management environment. Health Aff (Millwood). 2008; 27:103-12.
PubMed
CrossRef
 
Choudhry NK, Fischer MA, Avorn J, Schneeweiss S, Solomon DH, Berman C, et al. At Pitney Bowes, value-based insurance design cut copayments and increased drug adherence. Health Aff (Millwood). 2010; 29:1995-2001.
PubMed
 
Maciejewski ML, Farley JF, Parker J, Wansink D. Copayment reductions generate greater medication adherence in targeted patients. Health Aff (Millwood). 2010; 29:2002-8.
PubMed
CrossRef
 
Choudhry NK, Avorn J, Glynn RJ, Antman EM, Schneeweiss S, Toscano M, et al, Post-Myocardial Infarction Free Rx Event and Economic Evaluation (MI FREEE) Trial. Full coverage for preventive medications after myocardial infarction. N Engl J Med. 2011; 365:2088-97.
PubMed
CrossRef
 
Zhang Y, Lave JR, Donohue JM, Fischer MA, Chernew ME, Newhouse JP. The impact of Medicare Part D on medication adherence among older adults enrolled in Medicare-Advantage products. Med Care. 2010; 48:409-17.
PubMed
CrossRef
 
Davidoff F, Batalden P, Stevens D, Ogrinc G, Mooney S, SQUIRE Development Group. Publication guidelines for quality improvement in health care: evolution of the SQUIRE project. Qual Saf Health Care. 2008; 17:Suppl 1i3-9.
PubMed
CrossRef
 

Letters

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Comments

Submit a Comment
Submit a Comment

Supplements

Supplemental Content
Supplement 1.

Summary of Results for Patient, Provider, and Systems Interventions

Supplemental Content
Supplement 2.

Medication Adherence Intervention Characteristics

Summary for Patients

Clinical Slide Sets

Terms of Use

The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.

Toolkit

Want to Subscribe?

Learn more about subscription options

Advertisement
Related Articles
Related Point of Care
Topic Collections
PubMed Articles

Want to Subscribe?

Learn more about subscription options

Forgot your password?
Enter your username and email address. We'll send you a reminder to the email address on record.
(Required)
(Required)