The full benefit of many effective medications will be achieved only if patients adhere to prescribed treatment regimens. Unfortunately, applying terms such as “noncompliant” and “nonadherent” to patients who do not consume every pill at the desired time can stigmatize them in their future relationships with health care providers. This article on medication adherence (or compliance) reviews strategies to assess and enhance this important aspect of patient care.

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Adherence to Medication

Background
People who are prescribed self-administered medications typically take less than half the prescribed doses. Efforts to assist patients with adherence to medications might improve the benefits of prescribed medications, but also might increase their adverse effects.

Objectives
To update a review summarizing the results of randomized controlled trials (RCTs) of interventions to help patients follow prescriptions for medications for medical problems, including mental disorders but not addictions.

Search methods
We updated searches of The Cochrane Library, MEDLINE, CINAHL, EMBASE, International Pharmaceutical Abstracts (IPA), PsycINFO (all via OVID) and Sociological Abstracts (via CSA) in January 2007 with no language restriction. We also reviewed bibliographies in articles on patient adherence and articles in our personal collections, and contacted authors of relevant original and review articles.

Selection criteria
Articles were selected if they reported an unconfounded RCT of an intervention to improve adherence with prescribed medications, measuring both medication adherence and treatment outcome, with at least 80% follow-up of each group studied and, for long-term treatments, at least six months follow-up for studies with positive initial findings.

Data collection and analysis
Study design features, interventions and controls, and results were extracted by one review author and confirmed by at least one other review author. We extracted adherence rates and their measures of variance for all methods of measuring adherence in each study, and all outcome rates and their measures of variance for each study group, as well as levels of statistical significance for differences between study groups, consulting authors and verifying or correcting analyses as needed. The studies differed widely according to medical condition, patient population, intervention, measures of adherence, and clinical outcomes. Therefore, we did not feel that quantitative analysis was scientifically justified; rather, we conducted a qualitative analysis.

Main results
For short-term treatments, four of ten interventions reported in nine RCTs showed an effect on both adherence and at least one clinical outcome, while one intervention reported in one RCT significantly improved patient adherence, but did not enhance the clinical outcome. For long-term treatments, 36 of 83 interventions reported in 70 RCTs were associated with improvements in adherence, but only 25 interventions led to improvement in at least one treatment outcome. Almost all of the interventions that were effective for long-term care were complex, including combinations of more convenient care, information, reminders, self-monitoring, reinforcement, counseling, family therapy, psychological therapy, crisis intervention, manual telephone follow-up, and supportive care. Even the most effective interventions did not lead to large improvements in adherence and treatment outcomes.

Authors' conclusions
For short-term treatments several quite simple interventions increased adherence and improved patient outcomes, but the effects were inconsistent from study to study with less than half of studies showing benefits. Current methods of improving adherence for chronic health problems are mostly complex and not very effective, so that the full benefits of treatment cannot be realized. High priority should be given to fundamental and applied research concerning innovations to assist patients to follow medication prescriptions for long-term medical disorders.

Interventions for enhancing medication adherence.

Objective To evaluate the relation between adherence to drug therapy, including placebo, and mortality. Design Meta-analysis of observational studies. Data sources Electronic databases, contact with investigators, and textbooks and reviews on adherence. Review methods Predefined criteria were used to select studies reporting mortality among participants with good and poor adherence to drug therapy. Data were extracted for disease, drug therapy groups, methods for measurement of adherence rate, definition for good adherence, and mortality. Results Data were available from 21 studies (46 847 participants), including eight studies with placebo arms (19 633 participants). Compared with poor adherence, good adherence was associated with lower mortality (odds ratio 0.56, 95% confidence interval 0.50 to 0.63). Good adherence to placebo was associated with lower mortality (0.56, 0.43 to 0.74), as was good adherence to beneficial drug therapy (0.55, 0.49 to 0.62). Good adherence to harmful drug therapy was associated with increased mortality (2.90, 1.04 to 8.11). Conclusion Good adherence to drug therapy is associated with positive health outcomes. Moreover, the observed association between good adherence to placebo and mortality supports the existence of the “healthy adherer” effect, whereby adherence to drug therapy may be a surrogate marker for overall healthy behaviour.

https://www.bmj.com/content/bmj/333/7557/15.full.pdf

A meta-analysis of the association between adherence to drug therapy and mortality

The 2008 BHIVA Guidelines have been updated to incorporate all the new relevant information (including presentations at the 15th Conference on Retroviruses and Opportunistic Infections 2008) since the last iteration. The guidelines follow the methodology outlined below and all the peer-reviewed publications and important, potentially treatment-changing abstracts from the last 2 years have been reviewed.


The translation of data into clinical practice is often difficult even with the best possible evidence (i.e. two randomized controlled trials) because of trial design, inclusion criteria and precise surrogate marker endpoints (see Appendix). The recommendations based upon expert opinion have the least good evidence but perhaps provide an important reason for writing the guidelines to produce a consensual opinion about current practice. It must, however, be appreciated that such opinion is often wrong and should not stifle research to challenge it.


Similarly, although the Writing Group seeks to provide guidelines to optimize treatment, such care needs to be individualized and we have not constructed a document that we would wish to see used as a ‘standard’ for litigation.

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British HIV Association guidelines for the treatment of HIV-1-infected adults with antiretroviral therapy 2008

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(10)61997-6.pdf

Effects of a mobile phone short message service on antiretroviral treatment adherence in Kenya (WelTel Kenya1): a randomised trial

A review of 77 studies employing self-report measures of antiretroviral adherence published 1/1996 through 8/2004 revealed great variety in adherence assessment item content, format, and response options. Recall periods ranged from 2 to 365 days (mode=7 days). The most common cutoff for optimal adherence was 100% (21/48 studies, or 44%). In 27 of 34 recall periods (79%), self-reported adherence was associated with adherence as assessed with other indirect measures. Data from 57 of 67 recall periods (84%) indicated self-reported adherence was significantly associated with HIV-1 RNA viral load; in 16 of 26 (62%), it was associated with CD4 count. Clearly, the field would benefit from item standardization and a priori definitions and operationalizations of adherence. We conclude that even brief self-report measures of antiretroviral adherence can be robust, and recommend items and strategies for HIV research and clinical management.

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Self-report measures of antiretroviral therapy adherence: A review with recommendations for HIV research and clinical management.

Nonadherence in the management of chronic illness is a pervasive clinical challenge. Although researchers have identified multiple correlates of adherence, the field remains relatively atheoretical. The authors propose a cognitive–affective model of medication adherence based on social support theory and research. Structural equation modeling of longitudinal survey data from 136 mainly African American and Puerto Rican men and women with HIV/AIDS provided preliminary support for a modified model. Specifically, baseline data indicated social support was associated with less negative affect and greater spirituality, which, in turn, were associated with self-efficacy to adhere. Self-efficacy to adhere at baseline predicted self-reported adherence at 3 months, which predicted chart-extracted viral load at 6 months. The findings have relevance for theory building, intervention development, and clinical practice.

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A Longitudinal Evaluation of a Social Support Model of Medication Adherence Among HIV-Positive Men and Women on Antiretroviral Therapy

Adherence has proven to be Achilles' heel of antiretroviral therapy. To achieve the nearly perfect adherence apparently necessary for optimal effects, individuals often require assistance. In this review, we examine antiretroviral therapy adherence intervention studies and reviews published through January 2003 as well as abstracts of ongoing National Institutes of Health-funded research projects aimed at enhancing antiretroviral therapy adherence. The 21 published studies we located utilized 4 intervention strategies: cognitive-behavioral, behavioral, directly observed therapy, and affective. Most of these were pilot or feasibility studies. However, the 4 randomized controlled trials conducted with adequate methologic rigor suggest some promising yet preliminary effects of a pharmacist-led individualized intervention, a cognitive-behavioral educational intervention based on self-efficacy theory, and cue-dose training when combined with monetary reinforcement. The 39 ongoing federally funded studies offer superior methodologic sophistication and include some innovative strategies, such as the use of handheld devices, two-way pagers, and alarmed medication vials, along with enhancement of social and emotional support.

Antiretroviral adherence interventions: a review of current literature and ongoing studies.

Objective: To determine the relative efficacy of peer support and pager messaging strategies versus usual care to improve medication adherence and clinical outcomes among HIV-positive outpatients initiating or switching to a new highly active antiretroviral therapy regimen. Design: A 2 × 2 factorial randomized controlled trial of a 3-month intervention with computer-assisted self-interviews and blood draws administered at baseline, 3, 6, and 9 months. Methods: HIV-positive patients at a public HIV specialty clinic in Seattle, WA (N = 224) were randomly assigned to peer support, pager messaging, both strategies, or usual care. The main outcomes were adherence according to self-report and electronic drug monitoring, CD4 count, and HIV-1 RNA viral load. Results: Intent-to-treat analyses suggested the peer intervention was associated with greater self-reported adherence at immediate postintervention. However, these effects were not maintained at follow-up assessment; nor were there significant differences in biological outcomes. The pager intervention, on the other hand, was not associated with greater adherence but was associated with improved biological outcomes at postintervention that were sustained at follow-up. Conclusions: Analyses indicate the potential efficacy of peer support and pager messaging to promote antiretroviral adherence and biological outcomes, respectively. More potent strategies still are needed.

Peer support and pager messaging to promote antiretroviral modifying therapy in Seattle: a randomized controlled trial.

Survey interviews were conducted with a random sample of 50 primarily indigent, African American and Puerto Rican men and women at an outpatient human immunodeficiency virus (HIV) clinic in the Bronx, New York. Analyses revealed a generally high rate of adherence according to self-report data (i.e., on average, participants reported taking 85% of their medications over the last 3 days). However, adherence to the correct number of pills, dosing schedules, and special instructions was more problematic. No sociodemographic or substance use indicators were associated with adherence. Compared to men, women reported higher scores on the Crowne-Marlowe Social Desirability Scale, which were positively correlated with self-reported adherence. "Forgot" (50%) and "felt worse" (46%) were the most common reasons for missed doses. Mediation analyses provided partial support for our proposed model of social support and adherence. Specifically, regression analyses controlling for social desirability indicated that need for social support was positively correlated with acknowledged nonadherence and that this relationship was mediated by self-efficacy and depressive symptomatology.

Pamela A. Frick

Papers

Self-report measures of antiretroviral therapy adherence: A review with recommendations for HIV research and clinical management.

A Longitudinal Evaluation of a Social Support Model of Medication Adherence Among HIV-Positive Men and Women on Antiretroviral Therapy

Antiretroviral adherence interventions: a review of current literature and ongoing studies.

Peer support and pager messaging to promote antiretroviral modifying therapy in Seattle: a randomized controlled trial.

Mediators of social support and antiretroviral adherence among an indigent population in New York City.