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Improving adherence and persistence: a review and assessment of interventions and description of steps toward a national adherence initiative.

OBJECTIVES: To identify the effectiveness of adherence interventions reported in the literature, to identify interventions being conducted and/or sponsored by large chain pharmacies and pharmaceutical manufacturers, and to seek input from a panel of pharmacists who address adherence issues on a daily basis as to the steps that should be taken to advance a national initiative to increase awareness of the importance of and opportunities associated with medication adherence and persistence. MAIN OUTCOME MEASURE: Effectiveness of the adherence interventions reported in the literature. METHODS: First, a literature search was conducted using MEDLINE, International Pharmaceutical Abstracts, CINAHL, and PsycINFO. Keywords were medication or drug and compliance or adherence or persistence and control group. Second, pharmaceutical manufacturers and chain pharmacies were surveyed. Third, an advisory panel reacted to the research findings and formulated a series of action steps that could support or be part of a national initiative to increase adherence. RESULTS: Reported adherence-related interventions were grouped into five categories--adherence aids, refill or follow-up reminders, regimen simplification, written and oral education, and comprehensive management. Median adherence increases ranged from 6% to 25% for these categories. Interviews with 10 chain pharmacies revealed that adherence is an important issue. Most chains have some form of adherence program in place, but current initiatives are product-focused rather than patient-focused. Interviews with 15 manufacturers revealed that they currently use a variety of adherence interventions and want to partner with pharmacies to implement and assess the initiatives. The advisory panel developed a series of action items for implementing a national adherence initiative. CONCLUSION: Comprehensive interventions can improve adherence and are mutually beneficial for patients, pharmacies, and manufacturers. Pharmacists must be able to assess patients' adherence, identify the reasons for nonadherence, and develop patient-specific interventions. Studies have shown that the most successful interventions have some follow-up component and address the underlying reason(s) for nonadherence. Pharmacies and pharmaceutical manufacturers have tried various adherence interventions, such as patient education and refill reminders. There is a growing sense that a national adherence initiative is needed to coordinate pharmacists' efforts to address this public health problem, and the American Pharmacists Association is well positioned to take a leadership role in such efforts.

Age Factors↗

Theory- and evidence-based intervention to improve adherence to antiretroviral therapy among HIV-infected patients in the Netherlands: a pilot study.

The objectives of this study were to describe and pilot-test a theory- and evidence-based intervention to improve adherence of HIV-infected patients with antiretroviral medication. Twenty-six treatment-experienced patients (>6 months on treatment) participated in a within-subject comparison design. Adherence was measured electronically with Medication Event Monitoring System (MEMS) caps for at least 5 months: 2 months before the intervention and 3 months during the intervention. MEMS data were used to measure the outcome of the intervention, but also served as feedback to participants during the intervention. Mean adherence during the month before intervention was compared to mean adherence during the third month of intervention. Data for the process evaluation were gathered through direct observation and semi-structured interviews. Adherence improved significantly during the intervention (Z = -2.1, p < 0.05). Mean adherence (percentage of prescribed doses taken within correct time interval) before the intervention was 81.8% compared to 92.5% during the third month of the intervention. More than 65% of the nonadherent patients (<95% adherence) before the intervention were adherent during the third month of the intervention. Both health care professionals and patients positively evaluated the intervention protocol and the electronic measurement of adherence. The only critique from some patients was the lack of userfriendliness of the MEMS cap and its medication container (size and shape). It can be concluded that the proposed intervention fits in standard care procedures, can be executed by trained HIV nurses, seems to improve adherence to antiretroviral medication, and is positively evaluated by the users. Large-scale and long-term research is warranted.

Adult↗

A design for testing interventions to improve adherence within a hypertension clinical trial.

The Potassium Adherence Clinical Trial (PACT) incorporates one randomized clinical trial within another. A randomized trial of interventions to increase adherence to medication is nested within a second randomized clinical trial testing hypotensive effect of supplemental oral potassium. The trial aims principally to compare the effects of three intervention strategies: two sessions of individual patient counseling, two telephone contacts, or standard care. The trial aims secondarily to evaluate the effect of 60 mEq supplemental oral potassium daily on sitting systolic and diastolic blood pressure in hypertensive patients on established drug therapy. Therefore, it organizes the patients given potassium into three study groups for adherence interventions, and the patients assigned to placebo into a further three. We evaluate adherence primarily by means of the Medication Event Monitoring System (MEMS), an electronic system that records the date and time that the container of study medication is opened. Additional measurements, such as assessments of change in levels of urinary potassium, pill counts, appointment records, self-reporting by patients, and estimates by physician of adherence, are used and correlated with MEMS data. At a single center, the trial enrolled 107 participants between the ages of 26 and 80. This paper describes the background to this trial within a trial, details its design, documents the baseline characteristics of participants enrolled, and describes issues experienced during implementation of the trial.

Adult↗

Interventions to improve adherence to lipid lowering medication.

BACKGROUND: Lipid lowering drugs are still widely underused, despite compelling evidence about their effectiveness in the treatment and prevention of cardiovascular disease. Poor patient adherence to medication regimen is a major factor in the lack of success in treating hyperlipidaemia. In this review we focus on interventions, which encourage patients at risk of heart disease or stroke to take lipid lowering medication regularly. OBJECTIVES: To assess the effect of interventions aiming at improved adherence to lipid lowering drugs, focusing on measures of adherence and clinical outcomes. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycInfo and CINAHL. Date of most recent search was in February 2003. No language restrictions were applied. SELECTION CRITERIA: Randomised controlled trials of adherence-enhancing interventions to lipid lowering medication in adults for both primary and secondary prevention of cardiovascular disease in an ambulatory setting. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data independently and assessed studies according to criteria outlined by the Cochrane Reviewers' Handbook. MAIN RESULTS: The eight studies found contained data on 5943 patients. Interventions could be stratified into four categories : 1. simplification of drug regimen, 2. patient information/education, 3. intensified patient care such as reminding and 4. complex behavioural interventions such as group sessions. Change in adherence ranged from -3% to 25% (decrease in adherence by 3% to increase in adherence by 25%). Three studies reported significantly improved adherence through simplification of drug regimen (category 1), improved patient information/education (category 2) and reminding (category 3). The fact that the successful interventions were evenly spread across the categories, does not suggest any advantage of one particular type of intervention. The methodological and analytical quality was generally low and results have to be considered with caution. Combining data was not appropriate due to the substantial heterogeneity between included randomised controlled trials (RCTs). REVIEWERS' CONCLUSIONS: At this stage, no specific intervention aimed at improving adherence to lipid lowering drugs can be recommended. The lack of a gold standard method of measuring adherence is one major barrier in adherence research. More reliable data might be achieved by newer methods of measurement, more consistency in adherence assessment and longer duration of follow-up. Increased patient-centredness with emphasis on the patient's perspective and shared-decision-making might lead to more conclusive answers when searching for tools to encourage patients to take lipid lowering medication.

Cardiovascular Diseases↗

Predictors of antiretroviral adherence as measured by self-report, electronic monitoring, and medication diaries.

This study reports on the prevalence and predictors of adherence as measured by self-report, medication diaries, and electronic monitoring. A sample of 180 patients receiving human immunodeficiency virus (HIV) antiretroviral therapy were randomized to one of three adherence surveillance methods (electronic monitoring caps, patient medication diaries, no surveillance control group) for 4 weeks, with adherence measured by self-report at study end point; 173 (96%) participants completed the study. Most participants were male (82%), non-white (68%), and unemployed (84%); mean self-reported CD4 count was 406 cells/mm,3 and 31% reported having undetectable viral load. The three methods of adherence measurement revealed moderate (electronic monitoring: 80.6%) to high (self-report: 93.7%; diaries: 92.6%) rates of adherence. Although there were differences across adherence measures, variables that were identified as correlates of lower adherence by all three methods included living with others or having a larger household, current symptomatology, and cognitive functioning deficits. This consensus across adherence measures strengthens the validity of these identified predictors and their potential value in informing the development of adherence interventions, as well as increases the validity of the three adherence measures.

Adult↗

Effect of a behavioral self-regulation intervention on patient adherence in hemodialysis.

The present study examined the efficacy of a behavioral intervention designed to increase adherence to fluid-intake restrictions among hemodialysis patients. Twenty intervention-group patients were compared with 20 matched control patients on an indicator of fluid-intake adherence at 3 time points. The Group x Time interaction was significant, indicating that patients in the 2 groups exhibited a differential pattern of change in fluid-intake adherence across the follow-up period. The intervention and control groups did not differ significantly in terms of adherence at the initial postintervention period but did differ at the 8-week follow-up. The observed group differences were, in part, due to a trend toward increasingly better adherence in the intervention group and poorer adherence in the control group across the follow-up period.

Adult↗

Failure of modified directly observed therapy combined with therapeutic drug monitoring to enhance antiretroviral adherence in a patient with major depression.

Improving medication nonadherence in HIV-infected patients with concomitant psychiatric issues remains a challenging therapeutic dilemma. One strategy may be to use a short course of modified directly observed therapy combined with therapeutic drug monitoring as an adherence intervention. Individual drug pharmacokinetics could be evaluated while the increased visit frequency is an opportunity to provide additional patient training and psychosocial support. We report our experience with a 43-year-old woman with severe depressive symptoms and persistent virologic failure despite appropriate therapy. Although the intervention was well-received by the patient, improvements in medication adherence behaviors waned over time. It should be recognized that not all patients are capable of achieving lifelong medication adherence and may benefit from continued supervised therapy.

Anti-HIV Agents↗

Meta-analysis of interventions for medication adherence to antihypertensives.

OBJECTIVE: To identify methods targeted at improving adherence to antihypertensives and determine their effect on adherence using meta-analytic techniques. METHODS: A literature search from 1970 to December 2000 using MEDLINE, International Pharmaceutical Abstracts, PsychLit, ERIC, and EMBASE was performed using the terms compliance, adherence, and medication. Randomized articles with an intervention directed at a patient/caregiver, a comparator group, and a minimum of 10 subjects in each intervention group were identified by 3 independent reviewers. Articles that did not report sample size data or adequate results of the intervention were excluded. Sixteen citations focusing on antihypertensive adherence were identified. Of the 16 citations, 6 studied either more than one intervention in the same population or different interventions in different patient populations, yielding 24 cohorts with 2446 patients. RESULTS: Fifty-eight percent of the methods focused on behavioral interventions (BIs), 29% studied the effect of a combination of behavioral and educational interventions (BEIs), and 13% utilized educational interventions (EIs) alone. Overall, the study groups were nonhomogenous (Q = 183.92; p < 0.001). However, when the groups were separated by the intervention type, the BIs were homogenous (Q = 1.19; p = 1.00) with an overall effect size (ES) of 0.04 (95% CI -0.01 to -0.09), indicating a trend toward improved adherence. Fifty percent of the BIs were performed in the physician's office; however, setting did not influence the intervention's impact (p = 0.13). Within the BIs, no single intervention improved adherence over others. CONCLUSIONS: Based on the interventions included in this meta-analysis, there is no single intervention that improves adherence to antihypertensives over others; therefore, a patient-specific approach should be modeled.

Antihypertensive Agents↗

A test of interventions to increase adherence to hypertensive medical regimens.

Low rates of adherence to hypertensive therapy limit patients' securing the full benefits of treatment. While some factors related to adherence have been identified research on the effectiveness of interventions to increase adherence levels is sparse. The present study was designed to assess the impact of a series of different interventions on a group of some 400 patients, all under the care of private physicians in a small community. A factorial design was employed to deliver four, sequential educational interventions, about four months apart, to randomly selected sub-groups. Interviews before and after each intervention provided information concerning self-reported adherence, health status, health beliefs, and personal characteristics. Pertinent medical records and pharmacy data were also obtained. The first intervention - printed material - did not significantly affect adherence. The second and fourth interventions - nurse telephone calls and social support - each increased medication taking and the third intervention - self-monitoring - led to better weight control. There was no cumulative impact of the interventions and different aspects of regimens were not significantly related to one another.

Antihypertensive Agents↗

Validity of a stage of change instrument in assessing medication adherence in indigent patients with HIV infection.

BACKGROUND: Adherence to antiretroviral therapy (ART) is vital to achieve durable suppression of viral replication. Effective mechanisms to predict adherence can be difficult to implement in clinical practice settings. Self-administered questionnaires are a practical option for assessing patient adherence but may lack validation with objective measures of adherence. OBJECTIVE: To examine the ability of a 2 item stage of change (SOC) questionnaire to predict medication adherence in indigent patients receiving ART. METHODS: Patients participating in an ongoing study to examine adherence interventions were administered a 2 item SOC instrument to assess readiness for adherence behavior. The SOC instrument was given to patients prior to beginning ART and readministered after they had received 16 weeks of treatment. Electronic monitoring was used to examine the validity of the SOC instrument to predict patient readiness for adherence behavior. RESULTS: Thirty-one patients completed the SOC questionnaire prior to beginning a new ART regimen. Most (87%) patients were male, had previously received antiretroviral therapy (77%), and had an AIDS diagnosis (77%). The SOC category determined at baseline was a poor predictor of adherence at 4 and 16 weeks; however, the SOC category determined after treatment onset (week 16) was a strong predictor of adherence at both time points (p < 0.001 for 4 and 16 weeks; one way ANOVA). CONCLUSIONS: The SOC category determined at baseline correlated poorly with subsequent medication adherence in our indigent, HIV-infected patient population. Prediction of adherence based on SOC after treatment initiation may provide a better estimate of adherence behavior. Recognition of this limitation may help clinicians more accurately interpret predicted adherence behavior from self-report instruments.

Adult↗

A qualitative study of persons who are 100% adherent to antiretroviral therapy.

This qualitative study examined the medication-taking behaviors and attitudes of participants determined to be 100% adherers to antiretroviral therapy from a NIH-funded study testing a 12-week telephone adherence intervention. Using open-ended questions, interviewers collected data on a sample of 13 informants, whose medication adherence to a randomly selected antiretroviral medication was 100%, based on a 30-day data collection using electronic event monitoring (EEM). The analysis revealed 'successful medication management' as the core category or main theme. The participants achieved success with medication adherence through managing specific areas (regimen, self and environment). By adopting realistic expectations and pragmatic attitudes, adherence is fostered when medication taking is a priority, when patients believe in the efficacy of their medications and when there is a strong patient/provider relationship. Future research is needed to develop tailored interventions using strategies identified by this population. Further in-depth examination of medication-taking behaviors in 100% adherers may be useful in developing individualized programs to maximize adherence to antiretroviral therapy in the clinical setting.

Adult↗

Adherence to highly active antiretroviral therapy in the homeless population in San Francisco: a prospective study.

BACKGROUND: We examined adherence to highly active antiretroviral therapy (HAART) in the homeless population, a population thought to be at high risk for poor adherence to therapy and for development of drug-resistant strains of human immunodeficiency virus (HIV). METHODS: We performed a 12-month prospective study of 148 persons receiving HAART who were identified in a stratified screening of the homeless and marginally housed. We sampled in lunch lines, shelters, and hotels in 3 neighborhoods of San Francisco, California. We used pill counts at unannounced home visits as the primary measure of adherence. RESULTS: Of 148 individuals sampled, 46 (31%) discontinued HAART during the study. Average adherence in the group of those who discontinued HAART was 51%, and 9% of these subjects had undetectable virus loads (i.e., <400 copies/mL) at the last follow-up visit. Predictors of discontinuation of therapy were depressive symptoms, injection drug use, African American ethnicity, and early poor adherence. Of 148 subjects, 102 (69%) continued to receive HAART throughout the study period. Average adherence in the group of those who continued to receive HAART was 74%, and 55% of these subjects had undetectable virus loads at the last follow-up visit. Predictors of lower average adherence in this group were African American ethnicity and use of crack cocaine; men who had sex with men had higher adherence. CONCLUSIONS: One-third of homeless and marginally housed persons receiving HAART discontinued therapy during the follow-up period and would benefit from adherence interventions directed at sustaining therapy; two-thirds continued to receive therapy at adherence levels comparable to those found with other clinical populations.

Adult↗

Impact of an interdisciplinary strategy on antibiotic use: a prospective controlled study in three hospitals.

OBJECTIVES: Evaluation of the impact of the implementation of practice guidelines, with or without their reinforcement by a pharmacist, on the intra-hospital use of antibiotics. MATERIALS AND METHODS: The duration of antibiotic treatment, their cost, and the length of patient stay were compared in three secondary-care hospitals, before and after interventions that were designed to promote rational antibiotic use. After randomization, hospital A received no intervention (control), local practice guidelines were implemented in hospital B (low grade intervention), and these guidelines were reinforced by a clinical pharmacist in hospital C (high grade intervention). Adherence to the guidelines was measured in hospitals B and C. Multivariable statistical analyses were carried out to adjust for confounding factors. RESULTS: None of the outcomes measured in the 1200 included patients decreased between the two study periods in any hospital. Hospital A was significantly and independently associated with an increase in the duration of antibiotic treatments, the cost of antibiotics (acquisition and global costs), and the length of stay. Although these differences were not statistically significant, increases in hospital B were higher than in hospital C. Adherence to guidelines was significantly higher in hospital C. CONCLUSIONS: Even though interdisciplinary interventions aiming at rationalizing antibiotic use could not diminish the duration of treatments, their costs or the length of stay, they proved useful to control the progression of these parameters.

Anti-Bacterial Agents↗

Effect of psychological intervention on exercise adherence in type 2 diabetic subjects.

Previous research has pointed to the efficacy of physical activity in individuals suffering from type 2 diabetes mellitus (type 2 DM). However, as with other populations, adherence to exercise programs is often problematic. This study assessed the effectiveness of a combination of exercise and psychological interventions in type 2 diabetics in terms of disease management and exercise adherence. Forty newly diagnosed type 2 diabetic subjects (54 +/- 6.5 years) took part in the study. Subjects were allocated to an exercise-only intervention (EO) or a combined exercise and psychological adherence intervention (EP) group. Adherence to the program was also monitored at a 6-month follow-up. The results confirmed a significant improvement in physiological parameters (total mass, fat mass, grip strength, peak flow, flexibility, and VO2 max) after the 12-week program in both groups (P < 0.001). The EP group had significant changes in body fat, grip strength, and peak flow (P < 0.05) in comparison to the EO group. Components of the visual analog mood scale (VAMS) were positively influenced in both groups from the therapy program (P < 0.001). The directed psychological intervention had a significant influence on attendance to the 12-week program (P < 0.001). This also resulted in significantly better adherence 6 months later (P < 0.05). In conclusion, the results have demonstrated that psychological intervention is of paramount importance for ensuring high adherence rates during exercise therapy for type 2 diabetic subjects.

Affect↗

Cost-effectiveness of an intervention to improve adherence to antiretroviral therapy in HIV-infected patients.

Adherence to antiretroviral medications has been shown to be an important factor in predicting viral suppression and clinical outcomes. The objective of this analysis was to assess the cost-effectiveness of a nursing intervention on antiretroviral adherence using data from a randomized controlled clinical trial as input to a computer-based simulation model of HIV disease. For a cohort of HIV-infected patients similar to those in the clinical trial (mean initial CD4 count of 319 cells/mm), implementing the nursing intervention in addition to standard care yielded a 63% increase in virologic suppression at 48 weeks. This produced increases in expected survival (from 94.5 to 100.9 quality-adjusted life months) and estimated discounted direct lifetime medical costs ($253,800 to $261,300). The incremental cost-effectiveness ratio for the intervention was $14,100 per quality-adjusted life year gained compared with standard care. Adherence interventions with modest effectiveness are likely to provide long-term survival benefit to patients and to be cost-effective compared with other uses of HIV care funds.

Adult↗

Abnormal cervical screen follow-up among low-income Latinas: Project SAFe.

BACKGROUND: Cervical cancer incidence and mortality rates are dramatically higher among low-income women than in the general population, in part due to poor adherence to recommended diagnostic follow-up after an index Pap test. This report describes a pilot study of the Screening Adherence Follow-Up Program (SAFe), an individualized, structured case management program designed to assess for and intervene in response to a variety of potential personal and systems barriers to follow-up adherence. Interventions included health education, counseling, and systems navigation. METHODS: A clinical decision-making algorithm was used to determine service intensity and level of intervention. Services were provided to 196 low-income women, predominantly Latinas, who had either a low-grade or high-grade squamous intraepithelial lesion (LGSIL or HGSIL) abnormal Pap result. Adherence rates to at least one follow-up appointment after enrollment and baseline intervention were 83% following LGSIL and 93% for HGSIL. RESULTS: Over 1 year post-enrollment, 41% of women with LGSIL were fully adherent, with 42% partially adherent; 61% of women with HGSIL were fully adherent, with 32% partially adherent. In a comparison group of 369 nonenrollees (women who refused participation or could not be located for consent), adherence rates were 58% for LGSIL and 67% for HGSIL. A survey among a random sample of women served indicated that 93% were "mostly" or "very" satisfied, overall, with SAFe services. CONCLUSIONS: The intervention team--a peer counselor and a master's degreed social worker--addressed multiple psychosocial and systems navigation problems to reduce potential barriers to adherence, including knowledge, attitudinal, psychosocial, psychological distress, systems communication, and resource access problems. SAFe appears highly acceptable to women and may significantly enhance medical care management following an abnormal cervical screen for a carefully targeted group of women at risk for suboptimal follow-up adherence.

Adult↗

Improving adherence to antiretroviral therapy.

Antiretroviral therapy (ART) has transformed HIV infection into a treatable, chronic condition. However, the need to continue treatment for decades rather than years, calls for a long-term perspective of ART. Adherence to the regimen is essential for successful treatment and sustained viral control. Studies have indicated that at least 95% adherence to ART regimens is optimal. It has been demonstrated that a 10% higher level of adherence results in a 21% reduction in disease progression. The various factors affecting success of ART are social aspects like motivation to begin therapy, ability to adhere to therapy, lifestyle pattern, financial support, family support, pros and cons of starting therapy and pharmacological aspects like tolerability of the regimen, availability of the drugs. Also, the regimen's pill burden, dosing frequency, food requirements, convenience, toxicity and drug interaction profile compared with other regimens are to be considered before starting ART. The lack of trust between clinician and patient, active drug and alcohol use, active mental illness (e.g. depression), lack of patient education and inability of patients to identify their medications, lack of reliable access to primary medical care or medication are considered to be predictors of inadequate adherence. Interventions at various levels, viz. patient level, medication level, healthcare level and community level, boost adherence and overall outcome of ART.

Anti-Retroviral Agents↗