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Review Article |

Interventions to Enhance Medication Adherence in Chronic Medical Conditions:  A Systematic Review FREE

Sunil Kripalani, MD, MSc; Xiaomei Yao, MD; R. Brian Haynes, MD, PhD
[+] Author Affiliations

Author Affiliations: Division of General Medicine, Department of Internal Medicine, Emory University School of Medicine, Atlanta, Ga (Dr Kripalani); and Department of Clinical Epidemiology and Biostatistics (Drs Yao and Haynes) and Department of Medicine (Dr Haynes), McMaster University, Hamilton, Ontario.


Arch Intern Med. 2007;167(6):540-549. doi:10.1001/archinte.167.6.540.
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Published online

Background  Approximately 20% to 50% of patients are not adherent to medical therapy. This review was performed to summarize, categorize, and estimate the effect size (ES) of interventions to improve medication adherence in chronic medical conditions.

Methods  Randomized controlled trials published from January 1967 to September 2004 were eligible if they described 1 or more unconfounded interventions intended to enhance adherence with self-administered medications in the treatment of chronic medical conditions. Trials that reported at least 1 measure of medication adherence and 1 clinical outcome, with at least 80% follow-up during 6 months, were included. Study characteristics and results for adherence and clinical outcomes were extracted. In addition, ES was calculated for each outcome.

Results  Among 37 eligible trials (including 12 informational, 10 behavioral, and 15 combined informational, behavioral, and/or social investigations), 20 studies reported a significant improvement in at least 1 adherence measure. Adherence increased most consistently with behavioral interventions that reduced dosing demands (3 of 3 studies, large ES [0.89-1.20]) and those involving monitoring and feedback (3 of 4 studies, small to large ES [0.27-0.81]). Adherence also improved in 6 multisession informational trials (small to large ES [0.35-1.13]) and 8 combined interventions (small to large ES [absolute value, 0.43-1.20]). Eleven studies (4 informational, 3 behavioral, and 4 combined) demonstrated improvement in at least 1 clinical outcome, but effects were variable (very small to large ES [0.17-3.41]) and not consistently related to changes in adherence.

Conclusion  Several types of interventions are effective in improving medication adherence in chronic medical conditions, but few significantly affected clinical outcomes.

Figures in this Article

An estimated 20% to 50% of patients do not take their medications as prescribed and are said to be nonadherent or noncompliant with therapy.13 In the setting of chronic medical conditions such as hypertension and hypercholesterolemia, medication nonadherence leads to worse medical treatment outcomes, higher hospitalization rates, and increased health care costs.4,5 Because of this, adherence has been called “the key mediator between medical practice and patient outcomes.”6

Researchers have tested a variety of interventions to improve patient adherence, ranging from simple adjustments in the medication regimen to complex multidisciplinary interventions that address health system barriers and communication between patients and health care professionals.710 However, the overall quality of the literature is poor, with wide variability in study design, including patient population, outcome measure, and duration of follow-up.11 It is desirable to draw recommendations from a smaller set of high-quality studies.

In a recent review for the Cochrane Database,12 several simple interventions appeared to improve adherence with short-term regimens, such as a course of antibiotics. However, interventions to improve medication use for chronic conditions appeared less effective overall and were often multifaceted, making it more difficult to synthesize published evaluations.12 In this article, we extend the findings of the Cochrane review by providing a more detailed examination of interventions to improve adherence in chronic medical conditions. We offer a framework for categorizing these interventions and report their relative impact using a standardized measure of effect size (ES). The goal of this review is to help physicians better understand the strengths and limitations of tested interventions for improving long-term medication use and identify those that are most successful.

DATA SOURCES

Electronic searches of the published literature from January 1967 to September 2004 were conducted through MEDLINE, CINAHL, PsycINFO, SOCIOFILE, International Pharmaceutical Abstracts, EMBASE, and The Cochrane Library, without language restriction. The exact search strategy varied across databases and generally included terms for adherence (eg, compliance, noncompliance, adherence, dropouts, treatment refusal), medication use (eg, medication, medicine, drug, treatment, regimen, pharmacotherapy), and clinical trial design (eg, clinical trial, intervention, outcome, randomized, control). A full description of the search strategy is provided elsewhere.12

STUDY SELECTION

Reviewers screened citation titles, index terms, and abstracts (if available) to identify potentially relevant articles, which were retrieved for full-text review. Two reviewers independently assessed the articles for possible inclusion. Differences in assessment were resolved by discussion or with assistance from a third reviewer.

Articles were selected if they reported a randomized controlled trial that described 1 or more unconfounded interventions intended to enhance adherence with self-administered medications used in the treatment of chronic medical conditions. Confounding was judged to be present if study groups were treated unequally except for the intervention intended to enhance adherence (eg, patients in the intervention group received not only more encouragement to comply but also a different medication or dose than those in the control group). Included studies were required to report at least 1 measure of medication adherence and 1 clinical outcome, with at least 80% follow-up of participants during 6 months if the study results were initially positive. Studies with negative results and less than 6 months of follow-up were included because initial failure was unlikely to be followed by success. Studies of short-term regimens were included in the Cochrane review12 but excluded from the present analysis to permit a focus on chronic medical conditions, for which adherence is a greater concern. Trials that pertained to psychiatric disorders were excluded because adherence is generally lower in patients with psychiatric disorders and unique challenges may also be present, potentially limiting the generalizability of interventions tested in that context.13

DATA EXTRACTION

For each eligible study, 1 reviewer extracted features of the patient population, study design, interventions, and control, as well as results for adherence and clinical outcomes. When multiple time points were provided, data were extracted for the longest period of follow-up, provided follow-up remained at least 80%. Each extraction was confirmed by at least 1 other reviewer. Other articles on the same trial were retrieved, and authors were contacted as needed for additional details or verification of reported analyses.

DATA SYNTHESIS

The eligible studies differed substantially in patient population, intervention, adherence measure, and clinical outcome measure, making a pooling of results inappropriate. Instead, studies were grouped by intervention type, using a taxonomy developed from other sources.8,9,14,15Informational interventions described cognitive strategies designed primarily to educate and motivate patients by instructional means, based on the concept that patients who understand their condition and its treatment will be more informed, empowered, and likely to comply. Informational sessions conducted individually or in a group setting, as well as didactic and interactive approaches, were included. Examples of informational interventions are face-to-face oral, telephone, written, or audiovisual education; didactic group class; and mailed instructional material (not including reminders or prompts to comply). Behavioral interventions were strategies designed to influence behavior through shaping, reminding (cues), or rewarding desired behavior (reinforcement). Examples include skill building by a health care professional; pillboxes, calendars, a change in packaging, or other steps intended to remind the patient; changes in dosage schedule to simplify the regimen or tailor the regimen to the patient's daily routine (ie, reduce its behavioral demands); and rewards and reinforcement (eg, assessment of adherence with feedback to the patient). Family and social interventions involved social support strategies, whether provided by family or another group. Examples are support groups and family counseling. Group sessions that were primarily didactic or informational, rather than supportive, were categorized as informational. Combined interventions included features of 2 or 3 of the preceding categories. Each included study was classified by 1 author using these categories, descriptors, and examples. This classification was reviewed by at least 1 other author, and disagreements were resolved by consensus.

For each outcome, an ES (Cohen d) with 95% confidence interval was calculated from information provided in the article or obtained from the authors. The ESs compare the difference in effect between study groups, divided by the standard deviation of this difference, resulting in standard deviation units.16 This measure is independent of the method of measurement used, thus permitting comparison of different interventions across studies. In this way, ES provides more information than a simple test of significance comparing outcomes in intervention and control groups. The ES can be positive or negative, depending on the effect of the treatment on the particular outcome measure. If the study results are statistically significant, then the ES is generally significant as well.

We calculated ESs according to established methods.16,17 For studies that provided range instead of a standard deviation, we converted range to standard deviation.18 The absolute value of each statistically significant ES was categorized as very small (<0.20), small (0.20 to <0.50), medium (0.50 to <0.80), or large (≥0.80).16 We calculated ESs between each intervention and control group. Some studies had more than 2 arms and provided only an overall test of significance comparing results across experimental groups. In these cases, the significance of the ES for intervention-control pairs may have differed from the overall significance of results. Also, if study authors did not specify the number of patients involved in the final analysis, we used the baseline sample size of each group to calculate the ES. Calculating the ES in this way, analogous to an intention-to-treat analysis, may underestimate the true effect of the intervention.

The electronic searches returned 13 061 citations (including 458 review articles), 955 of which were judged to merit full-text review. A total of 38 articles describing 37 randomized controlled trials met all inclusion criteria, including 2 articles from the same trial.19,20 Among the included studies, 13 reported on 12 informational interventions,1931 10 on behavioral interventions,3241 and 15 on combined interventions.4256 None described purely family or social interventions (Figure).

Place holder to copy figure label and caption
Figure.

Study flow.

Graphic Jump Location

Most studies reported a single measure of adherence. However, the choice of measure varied widely, from self-report scales to more objective measures obtained by auditing refill rates, performing pill counts, and assessing the timing of prescription bottle opening by Medication Event Monitoring System caps. Approximately half of the studies reported a single clinical outcome, which also varied greatly, depending on the patient population.

The ES could be calculated in 30 studies for adherence outcomes and in 30 studies for clinical outcomes. Most studies (71% for adherence and 100% for clinical outcomes) that did not provide enough information to calculate the ES were not statistically significant, which illustrated a form of reporting bias.

INFORMATIONAL INTERVENTIONS

The studies of informational interventions each compared intensive education to limited education or usual care (Table 1). Sample size varied from 46 to 350. The interventions ranged in duration from a single session of less than 1 hour to several hours over many sessions. Counseling was provided by a physician, nurse, health educator, or pharmacist. Both individual and group sessions were described, sometimes in combination, and they were often accompanied by written materials.

Table Graphic Jump LocationTable 1. Informational Interventions

Half (6 of 12) of these studies reported a significant increase in at least 1 measure of adherence.1921,23,25,28,30 However, 3 of these 6 trials had mixed results. Gallefoss et al19,20 reported an improvement among only patients with asthma not those with chronic obstructive pulmonary disease. Levy et al25 demonstrated improvement in adherence only for severe, not mild, asthma attacks. In the study by Schaffer and Tian30 of 3 educational strategies, 2 were effective.

Among the 10 studies for which an ES for adherence outcomes could be calculated,1925,2831 a large ES was observed only in a trial conducted by Pradier et al28 of intensive, multisession counseling for human immunodeficiency virus (HIV) treatment adherence (ES, 1.13 for self-reported adherence). Four other studies1921,23,25 that provided counseling over multiple sessions had a small to medium ES (range, 0.35-0.68), and the remainder were not significant.

Most informational interventions (8 of 12) did not improve clinical outcomes. Of the 4 studies with at least 1 positive clinical result, 2 had a small ES (Pradier et al28: ES, −0.39 for HIV RNA level; Levy et al25: ES, 0.34 for asthma symptom scores). The other 2 trials had medium to large ESs (Gallefoss et al19,20: ES, 0.52 for forced expiratory volume in 1 second in patients with asthma; Cote et al22: ES, −0.64 for urgent asthma-related visits and 3.41 for peak expiratory flow). Each of these 4 studies provided fairly intensive counseling with reinforcement over time. Only the interventions used by Cote et al22 and Pradier et al28 consistently led to better clinical outcomes, despite the study by Cote et al having no effect on adherence owing to a high rate of adherence in the control group (97%). Gallefoss et al19,20 again saw improvement only among the asthma subgroup, and Levy et al25 had mixed results based on the clinical outcome measure.

BEHAVIORAL INTERVENTIONS

The sample size of the behavioral studies ranged from 27 to 497 (Table 2). The most common and effective forms of behavioral intervention were dosage simplification32,34,36 and repeated assessment of medication use with feedback.35,3739 Other trials tested specialized packaging,33 directly observed therapy,40 and cognitive behavior therapy,41 but none of these techniques significantly affected adherence or clinical outcomes.

All 3 trials of dosage simplification demonstrated an improvement in adherence, whether switching from 2 doses to 1 dose per day or from 4 to 2.32,34,36 The ESs that could be calculated were large (range, 0.89-1.20).34,36 The impact on clinical outcomes was mixed. Brown et al34 found a significantly higher percentage of patients reached their low-density lipoprotein cholesterol goal when prescribed extended-release niacin compared with the short-acting form (medium ES of 0.66). However, the study by Baird et al32 of once-daily metoprolol demonstrated no significant improvement in blood pressure, whereas Girvin et al36 actually found a trend toward increased blood pressure in the once-daily therapy group.

The 4 trials that involved assessment and feedback asked patients to monitor and report their medication use and/or blood pressure.35,3739 The 3 studies that then provided patients with tailored feedback, reinforcement, or rewards demonstrated a significant improvement in adherence (ESs small to large; range, 0.27-0.81).35,37,39 The fourth study, which simply made home blood pressure values available to the patient and physician, did not improve adherence.38 Only 1 study in this group produced a clear improvement in clinical outcomes (Marquez Contreras et al39: ES, 0.89 for total cholesterol and 0.78 for low-density lipoprotein cholesterol). Friedman and colleagues35 reported a decrease in the diastolic blood pressure only after controlling for baseline blood pressure in adjusted analyses (small ES of 0.29); they found no significant change for systolic blood pressure.

COMBINED INTERVENTIONS

Most (13 of 15) combined interventions included informational and behavioral components,4245,4755 and 2 joined social support strategies with either informational or behavioral elements (Table 3).46,56 Sample size again varied widely, from 37 to 1113. Of the 13 studies with informational and behavioral elements, 5 demonstrated improvement in all adherence measures,42,47,48,50,51 and 3 others reported mixed or nearly significant results.43,45,53 The significant effects ranged in size from small to large (absolute ES values of 0.43-1.20). No studies in this group were able to demonstrate a significant change in all measured clinical parameters, although several trials noted a significant improvement in at least 1 clinical outcome42,48,51,55 or a strong trend.53 The ESs ranged widely across studies (very small to large ES [0.17-1.58]). No consistent relationships were observed between intervention characteristics or disease state and the success of the interventions. For example, 3 trials implemented relatively similar interventions among patients with asthma, but their reported effects varied substantially.42,45,47 Regarding the 2 studies with strong social support elements, both successfully improved adherence (unable to calculate ES), but neither led to better clinical outcomes.46,56

In this systematic review of randomized controlled trials designed to enhance medication adherence in chronic medical conditions, 16 of 37 trials reported a consistent improvement in adherence.21,23,28,32,3437,39,42,4648,50,51,56 Four other studies noted a significant change in adherence among a particular patient subgroup, with some but not all of the adherence measures used, or in a certain arm of a study testing multiple interventions.19,20,25,30,43 Nine of the 20 trials that had some impact on adherence were able to demonstrate an improvement in some19,20,25,35,42,48,51 or all28,34,39 of the measured clinical outcomes. Of the 17 studies that did not show an improvement in adherence, 2 improved clinical outcomes; the apparent lack of effect on adherence in these studies was probably due to insensitive adherence measures or a ceiling effect.22,55

Previous reviews have found few if any consistent relationships between the characteristics and effectiveness of interventions to improve adherence.7 In the present study, categorization of the trials by intervention type (informational, behavioral, or combined informational, behavioral, and/or social support) and calculation of ESs permit a few general observations. Behavioral interventions that reduced the dosing demands of individual therapies consistently improved adherence with a large ES (0.89-1.20). Apart from this, other successful interventions usually contained multiple elements delivered over time. For example, 6 informational interventions that provided educational counseling over a few sessions and addressed self-care issues improved adherence with small to large ESs (0.35-1.13). Successful behavioral interventions based in monitoring and feedback and the most successful combined interventions also included various elements, such as self-management plans, reinforcement, and occasionally rewards.

Despite the ability of these interventions to improve adherence, however, a positive effect on clinical outcomes was demonstrated infrequently, and ESs pertaining to clinical outcomes were highly variable (very small to large ES [0.17-3.41]). Moreover, results for clinical outcomes were not consistently related to the magnitude of adherence results or the characteristics of the intervention. Unfortunately, many of the studies were relatively small and not sufficiently powered to detect differences in clinical outcomes. Thus, the results of many of the studies are indeterminate for clinical outcome, rather than clearly negative.

The adherence literature and present study had several additional limitations. First, because we included only published trials, the reported findings may overestimate the true effect of such interventions due to publication bias. Second, our inclusion criteria were somewhat stringent. Many studies with shorter follow-up or no measurement of clinical outcomes were excluded, and they are listed elsewhere.12 Third, our ability to categorize the trials into distinct modes of intervention was limited by the frequently complex nature of the interventions, requiring us to make judgments about the predominant components. Fourth, although we calculated ES and can make general comments about the magnitude of adherence and clinical outcome differences, the included studies were too heterogeneous to warrant pooling in a formal meta-analysis. Fifth, the literature review was completed in September 2004 and trials published since then may differ in their results, although they would be unlikely to substantially change the conclusions drawn from the 37 trials included in this review.

Because most of the available literature does not separate out the effects of the individual components of multifaceted interventions, it is not possible to draw definitive conclusions about which features of combined interventions are most beneficial. Additional research is needed to clarify which features are most responsible for changes in adherence and clinical outcomes, with the caveat that individual components may not prove powerful enough to show important effects. Future studies should also examine the effect of varying the intensity of interventions to determine dose-response relationships. Such findings would have important implications for health systems considering the implementation of patient adherence programs on a large scale. Investigations should be conducted with clinically meaningful outcomes as the primary end points and be sufficiently powered to detect a difference in these measures. Most important, future research should seek to understand the determinants of adherence behavior and to develop and test innovative ways to help people adhere to prescribed medication regimens, rather than persisting with existing approaches.

In summary, we found that several types of interventions are effective in improving medication adherence, but few were able to demonstrate an impact on clinical outcomes. Based on this review of the literature, the most effective interventions appear to be those that simplify dosing demands. Interventions that involve monitoring and feedback, as well as informational interventions delivered over multiple sessions, are probably also effective.

Correspondence: Sunil Kripalani, MD, MSc, Division of General Medicine, Department of Internal Medicine, Emory University School of Medicine, 49 Jesse Hill Jr Dr SE, Atlanta, GA 30303 (skripal@emory.edu).

Accepted for Publication: August 23, 2006.

Author Contributions: Dr Kripalani had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Kripalani and Haynes. Acquisition of data: Kripalani, Yao, and Haynes. Analysis and interpretation of data: Kripalani, Yao, and Haynes. Drafting of the manuscript: Kripalani, Yao, and Haynes. Critical revision of the manuscript for important intellectual content: Kripalani and Yao. Statistical analysis: Kripalani and Yao. Obtained funding: Haynes. Administrative, technical, and material support: Yao and Haynes. Study supervision: Kripalani and Haynes.

Financial Disclosure: None reported.

Funding/Support: Dr Kripalani was supported by a Mentored Patient-Oriented Research Career Development Award (grant K23 HL077597) and formerly by the Emory Mentored Clinical Research Scholars Program (National Institutes of Health/National Center for Research Resources grant K12 RR017643). Dr Haynes is supported by the Michael Gent Professorship.

Role of the Sponsors: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript.

Acknowledgment: We thank Stephen Walter, PhD, McMaster University, for his assistance with ES calculations and comments on an early draft of the manuscript. We also thank Heather McDonald, MSc, Aqeel Degani, MSc, and Amit Garg, MD, PhD, for their contributions to previous Cochrane reviews.

DiMatteo  MR Variations in patients' adherence to medical recommendations: a quantitative review of 50 years of research. Med Care 2004;42200- 209
PubMed Link to Article
Osterberg  LBlaschke  T Adherence to medication. N Engl J Med 2005;353487- 497
PubMed Link to Article
Haynes  RBedTaylor  DWedSackett  DLed Compliance in Health Care.  Baltimore, Md Johns Hopkins University Press1979;
DiMatteo  MRGiordani  PJLepper  HSCroghan  TW Patient adherence and medical treatment outcomes: a meta-analysis. Med Care 2002;40794- 811
PubMed Link to Article
Sokol  MCMcGuigan  KAVerbrugge  RREpstein  RS Impact of medication adherence on hospitalization risk and healthcare cost. Med Care 2005;43521- 530
PubMed Link to Article
Kravitz  RLMelnikow  J Medical adherence research: time for a change in direction? Med Care 2004;42197- 199
PubMed Link to Article
McDonald  HPGarg  AXHaynes  RB Interventions to enhance patient adherence to medication prescriptions: scientific review. JAMA 2002;2882868- 2879
PubMed Link to Article
Peterson  AMTakiya  LFinley  R Meta-analysis of trials of interventions to improve medication adherence. Am J Health Syst Pharm 2003;60657- 665
PubMed
Roter  DLHall  JAMerisca  RNordstrom  BCretin  DSvarstad  B Effectiveness of interventions to improve patient compliance: a meta-analysis. Med Care 1998;361138- 1161
PubMed Link to Article
Krueger  KPFelkey  BGBerger  BA Improving adherence and persistence: a review and assessment of interventions and description of steps toward a national adherence initiative. J Am Pharm Assoc 2003;43668- 678
PubMed Link to Article
Nichol  MBVenturini  FSung  JC A critical evaluation of the methodology of the literature on medication compliance. Ann Pharmacother 1999;33531- 540
PubMed Link to Article
Haynes  RBYao  XDegani  AKripalani  SGarg  AMcDonald  HP Interventions to enhance medication adherence. Cochrane Database Syst Rev 2005; ((4)) CD000011
PubMed
Haynes  RB Determinants of compliance: the disease and the mechanisms of treatment. Haynes  RBTaylor  DWSackett  DLCompliance in Health Care Baltimore, Md Johns Hopkins University Press1979;49- 62
Krousel-Wood  MHyre  AMuntner  PMorisky  D Methods to improve medication adherence in patients with hypertension: current status and future directions. Curr Opin Cardiol 2005;20296- 300
PubMed Link to Article
Walter  INutley  SMDavies  HTO Developing a taxonomy of interventions used to increase the impact of research. http://www.ruru.ac.uk/PDFs/Taxonomy%20development%20paper%20070103.pdf. Accessed November 29, 2005
Cohen  J Statistical Power Analysis for the Behavioral Sciences. 2nd ed. Hillsdale, NJ Lawrence Erlbaum Associates1988;
Hedges  LVOlkin  I Statistical Methods for Meta-analysis.  Orlando, Fla Academic Press1985;
Walter  SYao  X Effect sizes can be calculated for studies reporting ranges for outcome variables. J Clin Epidemiol In press
Gallefoss  FBakke  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;1602000- 2005
PubMed Link to Article
Gallefoss  FBakke  PSRsgaard  PK Quality of life assessment after patient education in a randomized controlled study on asthma and chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999;159812- 817
PubMed Link to Article
Canto de Cetina  TECanto  POrdonez Luna  M Effect of counseling to improve compliance in Mexican women receiving depot-medroxyprogesterone acetate. Contraception 2001;63143- 146
PubMed Link to Article
Cote  JBowie  DMRobichaud  PParent  JGBattisti  LBoulet  LP Evaluation of two different educational interventions for adult patients consulting with an acute asthma exacerbation. Am J Respir Crit Care Med 2001;1631415- 1419
PubMed Link to Article
Hill  JBird  HJohnson  S Effect of patient education on adherence to drug treatment for rheumatoid arthritis: a randomised controlled trial. Ann Rheum Dis 2001;60869- 875
PubMed
Laporte  SQuenet  SBuchmuller-Cordier  A  et al.  Compliance and stability of INR of two oral anticoagulants with different half-lives: a randomised trial. Thromb Haemost 2003;89458- 467
PubMed
Levy  MLRobb  MAllen  JDoherty  CBland  JMWinter  RJ A randomized controlled evaluation of specialist nurse education following accident and emergency department attendance for acute asthma. Respir Med 2000;94900- 908
PubMed Link to Article
Morice  AHWrench  C The role of the asthma nurse in treatment compliance and self-management following hospital admission. Respir Med 2001;95851- 856
PubMed Link to Article
Peterson  GMFitzmaurice  KDNaunton  MVial  JHStewart  KKrum  H Impact of pharmacist-conducted home visits on the outcomes of lipid-lowering drug therapy. J Clin Pharm Ther 2004;2923- 30
PubMed Link to Article
Pradier  CBentz  LSpire  B  et al.  Efficacy of an educational and counseling intervention on adherence to highly active antiretroviral therapy: French prospective controlled study. HIV Clin Trials 2003;4121- 131
PubMed Link to Article
Rawlings  MKThompson  MAFarthing  CF  et al. NZTA 4006 Helping to Enhance Adherence to Antiretroviral Therapy (HEART) Study Team, Impact of an educational program on efficacy and adherence with a twice-daily lamivudine/zidovudine/abacavir regimen in underrepresented HIV-infected patients. J Acquir Immune Defic Syndr 2003;34174- 183
PubMed Link to Article
Schaffer  SDTian  L Promoting adherence: effects of theory-based asthma education. Clin Nurs Res 2004;1369- 89
PubMed Link to Article
van Es  SMNagelkerke  AFColland  VTScholten  RJBouter  LM An intervention programme using the ASE-model aimed at enhancing adherence in adolescents with asthma. Patient Educ Couns 2001;44193- 203
PubMed Link to Article
Baird  MGBentley-Taylor  MMCarruthers  SG  et al.  A study of efficacy, tolerance and compliance of once-daily versus twice-daily metoprolol (Betaloc) in hypertension. Clin Invest Med 1984;795- 102
PubMed
Becker  LAGlanz  KSobel  EMossey  JZinn  SLKnott  KA A randomized trial of special packaging of antihypertensive medications. J Fam Pract 1986;22357- 361
PubMed
Brown  BGBardsley  JPoulin  D  et al.  Moderate dose, three-drug therapy with niacin, lovastatin, and colestipol to reduce low-density lipoprotein cholesterol <100 mg/dl in patients with hyperlipidemia and coronary artery disease. Am J Cardiol 1997;80111- 115
PubMed Link to Article
Friedman  RHKazis  LEJette  A  et al.  A telecommunications system for monitoring and counseling patients with hypertension. Impact on medication adherence and blood pressure control. Am J Hypertens 1996;9285- 292
PubMed Link to Article
Girvin  BMcDermott  BJJohnston  GD A comparison of enalapril 20 mg once daily versus 10 mg twice daily in terms of blood pressure lowering and patient compliance. J Hypertens 1999;171627- 1631
PubMed Link to Article
Haynes  RBSackett  DLGibson  ES  et al.  Improvement of medication compliance in uncontrolled hypertension. Lancet 1976;11265- 1268
PubMed Link to Article
Johnson  ALTaylor  DWSackett  DLDunnett  CWShimizu  AG Self-recording of blood pressure in the management of hypertension. CMAJ 1978;1191034- 1039
PubMed
Marquez Contreras  ECasado Martinez  JJCorchado Albalat  Y  et al.  Efficacy of an intervention to improve treatment compliance in hyperlipidemias. Aten Primaria 2004;33443- 450
PubMed Link to Article
Walley  JDKhan  MANewell  JNKhan  MH Effectiveness of the direct observation component of DOTS for tuberculosis: a randomised controlled trial in Pakistan. Lancet 2001;357664- 669
PubMed Link to Article
Weber  RChristen  LChristen  S  et al.  Effect of individual cognitive behaviour intervention on adherence to antiretroviral therapy: prospective randomized trial. Antivir Ther 2004;985- 95
PubMed
Bailey  WCRichards  JM  JrBrooks  CMSoong  SJWindsor  RAManzella  BA A randomized trial to improve self-management practices of adults with asthma. Arch Intern Med 1990;1501664- 1668
PubMed Link to Article
Berrien  VMSalazar  JCReynolds  EMcKay  KH. I. V. Medication Adherence Intervention Group, Adherence to antiretroviral therapy in HIV-infected pediatric patients improves with home-based intensive nursing intervention. AIDS Patient Care STDS 2004;18355- 363
PubMed Link to Article
Brus  HLvan de Laar  MATaal  ERasker  JJWiegman  O Effects of patient education on compliance with basic treatment regimens and health in recent onset active rheumatoid arthritis. Ann Rheum Dis 1998;57146- 151
PubMed Link to Article
Cote  JCartier  ARobichaud  P  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;1551509- 1514
PubMed Link to Article
Coull  AJTaylor  VHElton  RMurdoch  PSHargreaves  AD A randomised controlled trial of senior Lay Health Mentoring in older people with ischaemic heart disease: The Braveheart Project. Age Ageing 2004;33348- 354
PubMed Link to Article
Farber  HJOliveria  L Trial of an asthma education program in an inner-city pediatric emergency department. Pediatr Asthma Allergy Immunol 2004;17107- 115
Link to Article
Knobel  HCarmona  ALopez  JL  et al.  Adherence to very active antiretroviral treatment: impact of individualized assessment. Enferm Infecc Microbiol Clin 1999;1778- 81
PubMed
Nazareth  IBurton  AShulman  SSmith  PHaines  ATimberal  H A pharmacy discharge plan for hospitalized elderly patients—a randomized controlled trial. Age Ageing 2001;3033- 40
PubMed Link to Article
Peterson  GMMcLean  SMillingen  KS A randomised trial of strategies to improve patient compliance with anticonvulsant therapy. Epilepsia 1984;25412- 417
PubMed Link to Article
Piette  JDWeinberger  MMcPhee  SJMah  CAKraemer  FBCrapo  LM Do automated calls with nurse follow-up improve self-care and glycemic control among vulnerable patients with diabetes? Am J Med 2000;10820- 27
PubMed Link to Article
Sackett  DLHaynes  RBGibson  ES  et al.  Randomised clinical trial of strategies for improving medication compliance in primary hypertension. Lancet 1975;11205- 1207
PubMed Link to Article
Tuldra  AFumaz  CRFerrer  MJ  et al.  Prospective randomized two-arm controlled study to determine the efficacy of a specific intervention to improve long-term adherence to highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2000;25221- 228
PubMed Link to Article
Volume  CIFarris  KBKassam  RCox  CECave  A Pharmaceutical care research and education project: patient outcomes. J Am Pharm Assoc (Wash) 2001;41411- 420
PubMed
Weinberger  MMurray  MDMarrero  DG  et al.  Effectiveness of pharmacist care for patients with reactive airways disease: a randomized controlled trial. JAMA 2002;2881594- 1602
PubMed Link to Article
Wysocki  TGreco  PHarris  MABubb  JWhite  NH Behavior therapy for families of adolescents with diabetes: maintenance of treatment effects. Diabetes Care 2001;24441- 446
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure.

Study flow.

Graphic Jump Location

References

DiMatteo  MR Variations in patients' adherence to medical recommendations: a quantitative review of 50 years of research. Med Care 2004;42200- 209
PubMed Link to Article
Osterberg  LBlaschke  T Adherence to medication. N Engl J Med 2005;353487- 497
PubMed Link to Article
Haynes  RBedTaylor  DWedSackett  DLed Compliance in Health Care.  Baltimore, Md Johns Hopkins University Press1979;
DiMatteo  MRGiordani  PJLepper  HSCroghan  TW Patient adherence and medical treatment outcomes: a meta-analysis. Med Care 2002;40794- 811
PubMed Link to Article
Sokol  MCMcGuigan  KAVerbrugge  RREpstein  RS Impact of medication adherence on hospitalization risk and healthcare cost. Med Care 2005;43521- 530
PubMed Link to Article
Kravitz  RLMelnikow  J Medical adherence research: time for a change in direction? Med Care 2004;42197- 199
PubMed Link to Article
McDonald  HPGarg  AXHaynes  RB Interventions to enhance patient adherence to medication prescriptions: scientific review. JAMA 2002;2882868- 2879
PubMed Link to Article
Peterson  AMTakiya  LFinley  R Meta-analysis of trials of interventions to improve medication adherence. Am J Health Syst Pharm 2003;60657- 665
PubMed
Roter  DLHall  JAMerisca  RNordstrom  BCretin  DSvarstad  B Effectiveness of interventions to improve patient compliance: a meta-analysis. Med Care 1998;361138- 1161
PubMed Link to Article
Krueger  KPFelkey  BGBerger  BA Improving adherence and persistence: a review and assessment of interventions and description of steps toward a national adherence initiative. J Am Pharm Assoc 2003;43668- 678
PubMed Link to Article
Nichol  MBVenturini  FSung  JC A critical evaluation of the methodology of the literature on medication compliance. Ann Pharmacother 1999;33531- 540
PubMed Link to Article
Haynes  RBYao  XDegani  AKripalani  SGarg  AMcDonald  HP Interventions to enhance medication adherence. Cochrane Database Syst Rev 2005; ((4)) CD000011
PubMed
Haynes  RB Determinants of compliance: the disease and the mechanisms of treatment. Haynes  RBTaylor  DWSackett  DLCompliance in Health Care Baltimore, Md Johns Hopkins University Press1979;49- 62
Krousel-Wood  MHyre  AMuntner  PMorisky  D Methods to improve medication adherence in patients with hypertension: current status and future directions. Curr Opin Cardiol 2005;20296- 300
PubMed Link to Article
Walter  INutley  SMDavies  HTO Developing a taxonomy of interventions used to increase the impact of research. http://www.ruru.ac.uk/PDFs/Taxonomy%20development%20paper%20070103.pdf. Accessed November 29, 2005
Cohen  J Statistical Power Analysis for the Behavioral Sciences. 2nd ed. Hillsdale, NJ Lawrence Erlbaum Associates1988;
Hedges  LVOlkin  I Statistical Methods for Meta-analysis.  Orlando, Fla Academic Press1985;
Walter  SYao  X Effect sizes can be calculated for studies reporting ranges for outcome variables. J Clin Epidemiol In press
Gallefoss  FBakke  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;1602000- 2005
PubMed Link to Article
Gallefoss  FBakke  PSRsgaard  PK Quality of life assessment after patient education in a randomized controlled study on asthma and chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999;159812- 817
PubMed Link to Article
Canto de Cetina  TECanto  POrdonez Luna  M Effect of counseling to improve compliance in Mexican women receiving depot-medroxyprogesterone acetate. Contraception 2001;63143- 146
PubMed Link to Article
Cote  JBowie  DMRobichaud  PParent  JGBattisti  LBoulet  LP Evaluation of two different educational interventions for adult patients consulting with an acute asthma exacerbation. Am J Respir Crit Care Med 2001;1631415- 1419
PubMed Link to Article
Hill  JBird  HJohnson  S Effect of patient education on adherence to drug treatment for rheumatoid arthritis: a randomised controlled trial. Ann Rheum Dis 2001;60869- 875
PubMed
Laporte  SQuenet  SBuchmuller-Cordier  A  et al.  Compliance and stability of INR of two oral anticoagulants with different half-lives: a randomised trial. Thromb Haemost 2003;89458- 467
PubMed
Levy  MLRobb  MAllen  JDoherty  CBland  JMWinter  RJ A randomized controlled evaluation of specialist nurse education following accident and emergency department attendance for acute asthma. Respir Med 2000;94900- 908
PubMed Link to Article
Morice  AHWrench  C The role of the asthma nurse in treatment compliance and self-management following hospital admission. Respir Med 2001;95851- 856
PubMed Link to Article
Peterson  GMFitzmaurice  KDNaunton  MVial  JHStewart  KKrum  H Impact of pharmacist-conducted home visits on the outcomes of lipid-lowering drug therapy. J Clin Pharm Ther 2004;2923- 30
PubMed Link to Article
Pradier  CBentz  LSpire  B  et al.  Efficacy of an educational and counseling intervention on adherence to highly active antiretroviral therapy: French prospective controlled study. HIV Clin Trials 2003;4121- 131
PubMed Link to Article
Rawlings  MKThompson  MAFarthing  CF  et al. NZTA 4006 Helping to Enhance Adherence to Antiretroviral Therapy (HEART) Study Team, Impact of an educational program on efficacy and adherence with a twice-daily lamivudine/zidovudine/abacavir regimen in underrepresented HIV-infected patients. J Acquir Immune Defic Syndr 2003;34174- 183
PubMed Link to Article
Schaffer  SDTian  L Promoting adherence: effects of theory-based asthma education. Clin Nurs Res 2004;1369- 89
PubMed Link to Article
van Es  SMNagelkerke  AFColland  VTScholten  RJBouter  LM An intervention programme using the ASE-model aimed at enhancing adherence in adolescents with asthma. Patient Educ Couns 2001;44193- 203
PubMed Link to Article
Baird  MGBentley-Taylor  MMCarruthers  SG  et al.  A study of efficacy, tolerance and compliance of once-daily versus twice-daily metoprolol (Betaloc) in hypertension. Clin Invest Med 1984;795- 102
PubMed
Becker  LAGlanz  KSobel  EMossey  JZinn  SLKnott  KA A randomized trial of special packaging of antihypertensive medications. J Fam Pract 1986;22357- 361
PubMed
Brown  BGBardsley  JPoulin  D  et al.  Moderate dose, three-drug therapy with niacin, lovastatin, and colestipol to reduce low-density lipoprotein cholesterol <100 mg/dl in patients with hyperlipidemia and coronary artery disease. Am J Cardiol 1997;80111- 115
PubMed Link to Article
Friedman  RHKazis  LEJette  A  et al.  A telecommunications system for monitoring and counseling patients with hypertension. Impact on medication adherence and blood pressure control. Am J Hypertens 1996;9285- 292
PubMed Link to Article
Girvin  BMcDermott  BJJohnston  GD A comparison of enalapril 20 mg once daily versus 10 mg twice daily in terms of blood pressure lowering and patient compliance. J Hypertens 1999;171627- 1631
PubMed Link to Article
Haynes  RBSackett  DLGibson  ES  et al.  Improvement of medication compliance in uncontrolled hypertension. Lancet 1976;11265- 1268
PubMed Link to Article
Johnson  ALTaylor  DWSackett  DLDunnett  CWShimizu  AG Self-recording of blood pressure in the management of hypertension. CMAJ 1978;1191034- 1039
PubMed
Marquez Contreras  ECasado Martinez  JJCorchado Albalat  Y  et al.  Efficacy of an intervention to improve treatment compliance in hyperlipidemias. Aten Primaria 2004;33443- 450
PubMed Link to Article
Walley  JDKhan  MANewell  JNKhan  MH Effectiveness of the direct observation component of DOTS for tuberculosis: a randomised controlled trial in Pakistan. Lancet 2001;357664- 669
PubMed Link to Article
Weber  RChristen  LChristen  S  et al.  Effect of individual cognitive behaviour intervention on adherence to antiretroviral therapy: prospective randomized trial. Antivir Ther 2004;985- 95
PubMed
Bailey  WCRichards  JM  JrBrooks  CMSoong  SJWindsor  RAManzella  BA A randomized trial to improve self-management practices of adults with asthma. Arch Intern Med 1990;1501664- 1668
PubMed Link to Article
Berrien  VMSalazar  JCReynolds  EMcKay  KH. I. V. Medication Adherence Intervention Group, Adherence to antiretroviral therapy in HIV-infected pediatric patients improves with home-based intensive nursing intervention. AIDS Patient Care STDS 2004;18355- 363
PubMed Link to Article
Brus  HLvan de Laar  MATaal  ERasker  JJWiegman  O Effects of patient education on compliance with basic treatment regimens and health in recent onset active rheumatoid arthritis. Ann Rheum Dis 1998;57146- 151
PubMed Link to Article
Cote  JCartier  ARobichaud  P  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;1551509- 1514
PubMed Link to Article
Coull  AJTaylor  VHElton  RMurdoch  PSHargreaves  AD A randomised controlled trial of senior Lay Health Mentoring in older people with ischaemic heart disease: The Braveheart Project. Age Ageing 2004;33348- 354
PubMed Link to Article
Farber  HJOliveria  L Trial of an asthma education program in an inner-city pediatric emergency department. Pediatr Asthma Allergy Immunol 2004;17107- 115
Link to Article
Knobel  HCarmona  ALopez  JL  et al.  Adherence to very active antiretroviral treatment: impact of individualized assessment. Enferm Infecc Microbiol Clin 1999;1778- 81
PubMed
Nazareth  IBurton  AShulman  SSmith  PHaines  ATimberal  H A pharmacy discharge plan for hospitalized elderly patients—a randomized controlled trial. Age Ageing 2001;3033- 40
PubMed Link to Article
Peterson  GMMcLean  SMillingen  KS A randomised trial of strategies to improve patient compliance with anticonvulsant therapy. Epilepsia 1984;25412- 417
PubMed Link to Article
Piette  JDWeinberger  MMcPhee  SJMah  CAKraemer  FBCrapo  LM Do automated calls with nurse follow-up improve self-care and glycemic control among vulnerable patients with diabetes? Am J Med 2000;10820- 27
PubMed Link to Article
Sackett  DLHaynes  RBGibson  ES  et al.  Randomised clinical trial of strategies for improving medication compliance in primary hypertension. Lancet 1975;11205- 1207
PubMed Link to Article
Tuldra  AFumaz  CRFerrer  MJ  et al.  Prospective randomized two-arm controlled study to determine the efficacy of a specific intervention to improve long-term adherence to highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2000;25221- 228
PubMed Link to Article
Volume  CIFarris  KBKassam  RCox  CECave  A Pharmaceutical care research and education project: patient outcomes. J Am Pharm Assoc (Wash) 2001;41411- 420
PubMed
Weinberger  MMurray  MDMarrero  DG  et al.  Effectiveness of pharmacist care for patients with reactive airways disease: a randomized controlled trial. JAMA 2002;2881594- 1602
PubMed Link to Article
Wysocki  TGreco  PHarris  MABubb  JWhite  NH Behavior therapy for families of adolescents with diabetes: maintenance of treatment effects. Diabetes Care 2001;24441- 446
PubMed Link to Article

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