Interventions for enhancing medication adherence
Abstract
Background
People who are prescribed self administered medications typically take only about half their prescribed doses. Efforts to assist patients with adherence to medications might improve the benefits of prescribed medications.
Objectives
The primary objective of this review is to assess the effects of interventions intended to enhance patient adherence to prescribed medications for medical conditions, on both medication adherence and clinical outcomes.
Search methods
We updated searches of The Cochrane Library, including CENTRAL (via http://onlinelibrary.wiley.com/cochranelibrary/search/), MEDLINE, EMBASE, PsycINFO (all via Ovid), CINAHL (via EBSCO), and Sociological Abstracts (via ProQuest) on 11 January 2013 with no language restriction. We also reviewed bibliographies in articles on patient adherence, and contacted authors of relevant original and review articles.
Selection criteria
We included unconfounded RCTs of interventions to improve adherence with prescribed medications, measuring both medication adherence and clinical 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 findings at earlier time points.
Data collection and analysis
Two review authors independently extracted all data and a third author resolved disagreements. The studies differed widely according to medical condition, patient population, intervention, measures of adherence, and clinical outcomes. Pooling results according to one of these characteristics still leaves highly heterogeneous groups, and we could not justify meta‐analysis. Instead, we conducted a qualitative analysis with a focus on the RCTs with the lowest risk of bias for study design and the primary clinical outcome.
Main results
The present update included 109 new RCTs published since the previous update in January 2007, bringing the total number of RCTs to 182; we found five RCTs from the previous update to be ineligible and excluded them. Studies were heterogeneous for patients, medical problems, treatment regimens, adherence interventions, and adherence and clinical outcome measurements, and most had high risk of bias. The main changes in comparison with the previous update include that we now: 1) report a lack of convincing evidence also specifically among the studies with the lowest risk of bias; 2) do not try to classify studies according to intervention type any more, due to the large heterogeneity; 3) make our database available for collaboration on sub‐analyses, in acknowledgement of the need to make collective advancement in this difficult field of research. Of all 182 RCTs, 17 had the lowest risk of bias for study design features and their primary clinical outcome, 11 from the present update and six from the previous update. The RCTs at lowest risk of bias generally involved complex interventions with multiple components, trying to overcome barriers to adherence by means of tailored ongoing support from allied health professionals such as pharmacists, who often delivered intense education, counseling (including motivational interviewing or cognitive behavioral therapy by professionals) or daily treatment support (or both), and sometimes additional support from family or peers. Only five of these RCTs reported improvements in both adherence and clinical outcomes, and no common intervention characteristics were apparent. Even the most effective interventions did not lead to large improvements in adherence or clinical outcomes.
Authors' conclusions
Across the body of evidence, effects were inconsistent from study to study, and only a minority of lowest risk of bias RCTs improved both adherence and clinical outcomes. Current methods of improving medication adherence for chronic health problems are mostly complex and not very effective, so that the full benefits of treatment cannot be realized. The research in this field needs advances, including improved design of feasible long‐term interventions, objective adherence measures, and sufficient study power to detect improvements in patient‐important clinical outcomes. By making our comprehensive database available for sharing we hope to contribute to achieving these advances.
PICOs
Plain language summary
Ways to help people follow prescribed medicines
Background
Patients who are prescribed medicines take only about half of their doses and many stop treatment entirely. Assisting patients to adhere better to medicines could improve their health, and many studies have tested ways to achieve this.
Question
We updated our review from 2007 to answer the question: What are the findings of high‐quality studies that tested ways to assist patients with adhering to their medicines?
Search strategy
We retrieved studies published until 11 January 2013. To find relevant studies we searched six online databases and references in other reviews, and we contacted authors of relevant studies and reviews.
Selection criteria
We selected studies reporting a randomized controlled trial (RCT) comparing a group receiving an intervention to improve medicine adherence with a group not receiving the intervention. We included trials if they measured both medicine adherence and a clinical outcome (e.g. blood pressure), with at least 80% of patients studied until the end.
Main results
The studies differed widely regarding included patients, treatments, adherence intervention types, medicine adherence measurement, and clinical outcomes. Therefore, we could not combine the results in statistical analysis to reach general conclusions, as it would be misleading to suggest that they are comparable. Instead, we provide the key features and findings of each study in tables, and we describe intervention effects in studies of the highest quality. The present update included 109 new studies, bringing the total number to 182. In the 17 studies of the highest quality, interventions were generally complex with several different ways to try to improve medicine adherence. These frequently included enhanced support from family, peers, or allied health professionals such as pharmacists, who often delivered education, counseling, or daily treatment support. Only five of these RCTs improved both medicine adherence and clinical outcomes, and no common characteristics for their success could be identified. Overall, even the most effective interventions did not lead to large improvements.
Authors' conclusions
Characteristics and effects of interventions to improve medicine adherence varied among studies. It is uncertain how medicine adherence can consistently be improved so that the full health benefits of medicines can be realized. We need more advanced methods for researching ways to improve medicine adherence, including better interventions, better ways of measuring adherence, and studies that include sufficient patients to draw conclusions on clinically important effects.
Authors' conclusions
Background
Description of the condition
Low patient adherence is a major barrier to realizing the benefits of medications that have been shown to do more good than harm in clinical trials. Such trials are typically done among patients who are volunteers, and who are followed closely to assure high adherence. Benefits are greatly reduced or nullified in usual clinical practice where adherence rates are low. Interventions to improve adherence have the potential to multiply benefits for patients, but at the time of our previous review, Haynes 2008, no method of helping patients to follow self administered long‐term treatments had been proven effective, actionable, and affordable in usual care settings.
Many patients stop taking their medication in the first months following initiation, often without informing their provider, with further attrition over time. In addition, many patients who continue their medication do not consistently take it as prescribed. As a result, adherence rates average around 50% and range from 0% to over 100%, and there is no evidence for substantial change in the past 50 years (Sackett 1979; Gialamas 2009; Naderi 2012).
Medication non‐adherence is often defined as taking less than 80% of prescribed doses, although it has to be noted that non‐adherence can also include taking too many doses, and it is associated with an increased risk for poor health, adverse clinical events, and mortality. Thus many people who could benefit from medications do not, and much of the public and private investment in health research and health care is undermined. To make matters worse, low adherence, even to placebo, is independently associated with an increased risk of death ('healthy adherer' effect) (Simpson 2006). Therefore, enhancing medication adherence is a priority and could improve patient outcomes, primarily through the effect of medications, but also possibly through the overall 'healthy adherer' effect.
Description of the intervention
Our most recent update (search until January 2007) of this Cochrane review included 78 randomized controlled trials (RCTs) that had ≥ 80% follow‐up and tested the effect of adherence interventions on both adherence and clinical outcomes (Haynes 2008). We believe it is essential to have measures of both adherence and clinical outcomes, as ethical standards for adherence research dictate that attempts to improve adherence should be judged by their clinical benefits (NHLBI 1982). Studies that measure only adherence cannot show that patients are better off as a result, and studies that measure only clinical outcomes cannot verify that effects on adherence were important to achieving these outcomes.
Further, we described findings across disease conditions, as the clinical condition is not a major determinant of medication adherence, with the exception of psychiatric disorders (Haynes 1979a). Do note that studies targeting adherence for medications to treat psychiatric disorders are included in our review.
Our 2008 update found, besides the expected variety in medical conditions and regimens, a large diversity and complexity of interventions and of measures for adherence and patient outcomes (Haynes 2008). Although some intervention types tended to improve adherence, no specific recommendations could be given, especially since high‐quality evidence for consistent effects on both adherence and patient outcomes was lacking.
Why it is important to do this review
With increasing numbers of efficacious self administered treatments being available, the need for effective interventions to improve adherence is ever more apparent. In recent years, research efforts to better understand the multifactorial barriers that influence patient adherence and to refine theoretical frameworks have been increasing. However, whether these efforts have led to the emergence of more effective interventions needs to be assessed by summarizing the high‐quality RCT evidence to date. Many systematic reviews have been published after our 2008 update, but all focused on a specific (demographic, disease, or medication) population, intervention, or on an even more specific combination of both. Generally, these reviews reported similar conclusions: some intervention components are potentially effective, but small sample sizes and suboptimal methodology often prevented strong conclusions; the variety of adherence measures limited study comparability; and most studies lacked a theoretical underpinning (van Dulmen 2007).
Considering the substantial efforts in adherence research since 2007, and inconclusive evidence from other recent systematic reviews, we have updated our comprehensive systematic review. Based on publication rates over time in the previous review update, we predicted that we would find at least 50 additional RCTs, and thereby potentially improve our confidence for specific conclusions and recommendations.
Objectives
The primary objective of this review is to assess the effects of interventions intended to enhance patient adherence to prescribed medications for medical conditions, on both medication adherence and clinical outcomes.
Methods
Criteria for considering studies for this review
Types of studies
This systematic review is an update of the review by Haynes et al (Haynes 2008), which searched for studies until February 2007. As of 24 November 2013, no other comprehensive adherence reviews were registered in the Cochrane Database or PROSPERO, the International Prospective Register of Systematic Reviews (http://www.crd.york.ac.uk/prospero/). We used a web‐based database management system, developed by the Health Information Research Unit at McMaster University, to facilitate screening, data extraction, adjudication of disagreements, author review and confirmation of data, production of data tables, and production of data files for future research use. This system has been successfully used in conducting and completing several large, complex systematic reviews (Haynes 2010).
Studies for this review were included if they were RCTs that provided unconfounded tests of interventions expected to affect adherence. A confounder is a characteristic that is extraneous to the primary question being addressed in the study, but which can influence the outcome and is unequally distributed between the groups being compared in the trial. For example, in one study (Colcher 1972), two groups received the same prescription for phenoxymethyl penicillin, but different instructions, providing an unconfounded comparison for the instructions, but a third group in the same trial received a different drug (penicillin G benzathine) by a different route (intramuscularly) with a different dose (1.2 million units) and schedule (one dose), making it impossible to separate out independent adherence effects of this regimen. Thus, only the unconfounded comparison of instructions for phenoxymethyl penicillin was included in the review.
Types of participants
Patients who were prescribed medication for a medical (including psychiatric) disorder, but not for addictions (as these adherence problems are typically of a different nature and much more severe).
Types of interventions
Interventions of any sort intended to affect adherence with prescribed, self administered medications.
Types of outcome measures
We included studies if they reported at least one medication adherence measure and at least one clinical outcome. Regarding follow‐up completion, studies needed to have at least 80% follow‐up at the end of the recommended treatment period for short‐term treatments, and at least 80% follow‐up during at least six months for long‐term treatments with initially positive results. For long‐term regimens, we included negative trials with less than six months follow‐up and at least 80% data completion on the grounds that initial failure is unlikely to be followed by success (Sackett 1979). The 80% data completion was required for both adherence and clinical outcomes, and for any outcome other than mortality, the denominator for determining data completion excluded those patients who died before the outcome assessment.
Search methods for identification of studies
We searched: The Cochrane Library including CENTRAL (via http://onlinelibrary.wiley.com/cochranelibrary/search/), MEDLINE, EMBASE, PsycINFO (all via Ovid), CINAHL (via EBSCO), and Sociological Abstracts (via ProQuest). We completed database searches for relevant articles on 11 January 2013, updating previous searches that were undertaken on: 1 September 1993; 12 December 1993; 1 June 1994; 30 June 1995; 28 February 1997; 31 July 1998; 15 August 2001; 30 September 2004; and 1 February 2007. We searched new publications since 1 January 2007, that is, having a one‐month overlap with the previous search. All databases were originally searched from their start date.
The search filters for each database, and from the current and previous update, are shown in Appendix 1. We checked articles cited in reviews and original studies of patient adherence. We contacted authors of included RCTs to identify additional studies.
We re‐assessed all RCTs included in the 2008 update for eligibility to carry over into the current update. Retrieved citations from the updated search entered a first screening stage. Based on the title and abstract, studies moved to the second screening stage if they met all five eligibility criteria or if there was uncertainty about their eligibility. In the second screening stage, assessment of the full text determined if studies were included in the review. At both screening stages, two independent review authors assessed eligibility, and an adjudicator resolved disagreements. We recorded reasons for excluding citations in the second screening stage. The PRISMA flow chart showing the results for selection of papers is provided in Figure 1.
Study flow diagram.
Data collection and analysis
We imported data from the 2008 review into the update database, and checked the data for accuracy. Extracted data included items as provided in the tables from the previous Cochrane review (Haynes 2008): the 'Characteristics of included studies' table (i.e. methods, participants, interventions, outcomes, additional notes pertaining to any one of the aforementioned items, detailed assessment of risk of bias), and the 'Adherence and outcome' table (i.e. clinical problem, intervention, control, effect on adherence outcome, effect on clinical outcome). We extracted the same items for new included studies. In addition, we extracted items from the Cochrane 'Risk of bias' tool for all included studies from the previous and current update (Higgins 2011). Two review authors independently extracted all new data, and an adjudicator resolved disagreements. We contacted primary or corresponding authors of all included RCTs to confirm extracted data and provide missing data.
We quantified review author agreement on study 'Risk of bias' criteria using the unweighted Cohen's kappa (k) coefficient (Fleiss 1981). We carried out all analyses using SPSS, version 20.0. When reporting results from individual studies, we cited the measures of association and P values reported in the studies. We interpreted P value < 0.05 as indicating statistical significance. Due to the extreme heterogeneity in clinical conditions, participant selection criteria, medical regimens, interventions, adherence measures, and clinical outcome measures, pooling results according to any of these characteristics would still leave highly heterogeneous groups. In support of this, we refer to the meta‐analysis reported by the Ascertaining Barriers for Compliance (ABC) project team, which exclusively focused on RCTs that measured adherence by means of electronic medication event monitoring systems (MEMS) and still found a very high heterogeneity of effects (I2 = 98.88%) (ABC Project Team 2012). Pooling of effects in our review was further undermined by the frequent use of complex interventions, which was already problematic for categorizing intervention types in the previous update. Studies also had very heterogeneous clinical outcomes; they also often lacked clearly defined primary outcomes. We could not justify even plotting intervention effects without pooling in meta‐analysis, as this would imply some degree of comparability among the studies. Rather, as a best case alternative, we conducted a narrative analysis of the studies with the lowest risk of bias, using the Cochrane 'Risk of bias' tool (Higgins 2011), for study design (random sequence generation and concealment of allocation), and for their primary clinical outcome (blinding of outcome assessor, as relevant for the outcome in question). We did not require low risk of bias for the primary adherence measure, as this would have resulted in discussion of very few studies, as most adherence measures have a high or uncertain risk of bias, notably because of lack of blinding.
We reported intervention effects in individual RCTs for all outcomes for a) adherence and b) clinical outcomes. We reported effects in the RCTs identified as low risk of bias as described by the authors, with a focus on the primary outcomes, and with comments on methodological issues that might have influenced results, such as absence of correction for multiple comparisons. We considered adherence and clinical outcomes to be the primary outcome if they were:
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indicated to be the primary outcome by the study author; OR
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used in the study power calculation; OR
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the first outcome described in the 'Results' section of the article.
Results
Description of studies
Results of the search
The new search identified 26,312 citations of which we assessed 1673 in full text. Of these, we included 109, based on a full‐text review in the second screening phase. The PRISMA flow chart shows the results for selection of papers and is provided in Figure 1.
Included studies
The previous update included 78 RCTs, of which 73 were carried over into the current update. We excluded five previously included RCTs: in the course of this review update, we identified that two did not address self administered medication (Canto De Cetina 2001; Ran 2003), one had less than 80% follow‐up (Van Servellen 2005), one reported no data for clinical outcome (van Es 2001), and one was confounded (Piette 2001). Therefore, we included a total of 182 RCTs in the current update. The overall number of RCT participants was 46,962. However, this overall number does not reflect the strength of the evidence base, considering that we could not meaningfully combine results of included studies. The newly added studies represent a growth in the knowledge base of 150% in the past six years, with more than twice the number of trials than we had predicted based on publication rates in the 2008 review.
Key features of all 182 RCTs are summarized in the table Characteristics of included studies. The most frequently targeted conditions in all RCTs were:
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HIV/AIDS (36);
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psychiatric disorders (29);
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chronic obstructive pulmonary disease (27);
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cardiovascular disease or cardiovascular risk (21);
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hypertension (17); and
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diabetes (16).
The remaining studies targeted:
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dyslipidemia (6);
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antibiotics (4);
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arthritis (3);
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complex chronic care (3);
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dyspepsia (3);
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glaucoma (2);
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oral anticoagulation (2);
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osteoporosis (2);
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tuberculosis (2);
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acne (1);
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cancer (1);
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hepatitis (1);
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iron supplementation during pregnancy (1);
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liver transplant (1);
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malaria (1);
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oral contraceptives (1);
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tonsillectomy/adenoidectomy (1); and
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ulcerative colitis (1).
Among the 109 new RCTs, 80 were from high‐income countries (44 from USA), 17 from middle‐income countries, five from low‐income countries, and seven from unknown geographic locations (World Bank classification, http://data.worldbank.org/about/country‐classifications/country‐and‐lending‐groups). In a majority of new RCTs (67) the adherence intervention targeted more than one medication, while 27 targeted one medication (the number of medications was unknown for the remaining 15 RCTs).
There were substantive differences across studies in settings, clinical disorders, treatment regimens, adherence interventions, adherence measures, and clinical outcome measures, so that there was insufficient common ground for quantifying differences between groups or estimating pooled effect sizes that would permit meaningful quantitative analysis of findings across studies. Instead, we indicated which differences were statistically significant for adherence or clinical outcomes between the groups compared in each RCT (see Analysis 1.1). Of note, some of the negative results were unconvincing because of low statistical power: 44 RCTs did not meet the minimal required sample size of 60 patients per treatment group to detect an absolute difference of 25% in adherence with 80% power (Haynes 2008).
Excluded studies
Of the 26,312 unique citations detected, we excluded 24,639 studies during the title and abstract screen (Figure 1). We excluded an additional 1,564 studies during the full‐text screen (Figure 1), of which 374 were excluded at the data extraction stage for the reasons indicated in Characteristics of excluded studies. There are also eight studies awaiting assessment, as noted in Characteristics of studies awaiting classification.
Risk of bias in included studies
Although all included studies were RCTs, their risk of bias varied considerably because of study design or conduct. Review author agreement was good for determining risk of bias for random sequence generation (kappa = 0.71; 95% confidence interval (CI) 0.61 to 0.80), moderate for the risk of bias for allocation concealment (kappa = 0.47; 95% CI 0.34 to 0.59), and fair for the risk of bias for blinding of the primary clinical outcome assessor (kappa = 0.32; 95% CI 0.16 to 0.45). A third adjudicator resolved differences in the duplicate independent assessments. Authors responded to our requests to review our extractions and provide additional information on 126 occasions out of 182 attempts (69%).
Allocation
The risk of bias for random sequence generation was low in 105 RCTs and unclear in 77 RCTs. For concealment of allocation, risk of bias was high in two RCTs, low in 58 RCTs, and unclear in 122 RCTs.
Blinding
Also taking into account the risk of bias for the primary clinical outcome, 17 RCTs had a low risk of bias for both study design (random sequence generation and concealment of allocation) and for the primary clinical outcome (blinding of the outcome assessor): six from the previous update (Haynes 1976; Walley 2001; Nazareth 2001; Stevens 2002; Laporte 2003; Weber 2004), and 11 from the current update (Wu 2006; Simoni 2007; Martins 2009; Simoni 2009; Lester 2010; Chung 2011; Farooq 2011; Morgado 2011; Ellis 2012; Gray 2012; Solomon 2012). Only four RCTs also had a low risk of bias for the primary adherence outcome, since most adherence measures had a high or uncertain risk of bias (Haynes 1976; Chung 2011; Gray 2012; Solomon 2012).
We chose to focus our narrative on the 17 RCTs with low risk of bias for study design and primary clinical outcome to provide insights from the highest‐quality evidence of adherence intervention. Details for all 182 RCTs are reported in the table Characteristics of included studies.
A summary of the risk of bias in all 182 studies is shown in Figure 2.
'Risk of bias' summary: review authors' judgments about each risk of bias item for each included study.
Effects of interventions
Intervention effects
The diversity and complexity of interventions precluded a taxonomy of simple labels that would accurately summarize efficacy per intervention type. We also avoided the classification in general themes and groups as done for the previous update, as this would be more cumbersome and less helpful with the current volume of included randomized controlled trials (RCTs). Detailed information regarding treatment arms and outcomes for all 182 RCTs is provided in both the Characteristics of included studies and the Analysis 1.1 tables. To provide a reasonable sampling of the details and diversity of included adherence intervention RCTs, we chose to provide a narrative focused strictly on the RCTs with the lowest risk of bias.
Summary of the RCTs with the lowest risk of bias
Of all included RCTs, 17 had a low risk of bias for both the study design (random sequence generation and concealment of allocation) and the primary clinical outcome (blinding of outcome assessor, as relevant for the outcome). Four of these trials also had low risk of bias for measuring adherence, so we discuss these first, with the most recently published studies first, then the remaining 13 studies, again, with newest studies first.
Gray 2012 randomized 127 patients with newly diagnosed ocular hypertension or open‐angle glaucoma to an individually tailored adherence intervention or care as usual. The intervention was delivered by a glaucoma trained nurse with an initial session to assess patient needs, beliefs, and potential solutions, and to devise a one‐year individualized care plan that involved education, training, liaising with and training for informal caregivers and professional health care providers, and planning approximately five face‐to‐face or phone follow‐up contacts with the nurse for reassessment. From 12 to 24 months follow‐up no intervention was provided and both groups had usual care. The intervention group had a higher proportion of patients with 100% refill adherence (70% versus 43%; P value = 0.002) as measured by low risk of bias practitioner and pharmacist report at 12 months. Intraocular pressure values and changes in management were recorded from routine medical care charts. The mean intraocular pressure, and fluctuations in ocular pressure and changes in management, were not different at 12 months. At 24 months, adherence was not measured. The mean intraocular pressure was almost identical in the two groups, but the fluctuation of intraocular pressure was higher and changes in management more frequent in the control group. It is possible that the differences at 24 months were found due to chance, especially as it is unlikely that a significant effect would be observed one year after stopping the intervention, while no effect was observed after one year of intensive intervention.
Solomon 2012 sent seven informational mailings addressing osteoporosis to 2097 low‐income older adults who were initiating osteoporosis medication, and randomized them to receive eight phone counseling sessions by health educators using motivational interviewing techniques to promote adherence, or the mailings alone. The phone counseling intervention did not significantly improve the primary outcome, adherence as measured by the median medication possession ratio using low risk of bias pharmacy claims data. Further, secondary outcomes including medication persistence, and proportions with self reported fractures or falls were not improved. The authors indicated that the 113‐day time lag between identifying persons initiating therapy in the database and making the first phone call in the intervention group was a missed opportunity, since many eligible or recruited persons had already stopped therapy before the first call.
Chung 2011 randomized 400 newly diagnosed HIV patients who were candidates for highly active antiretroviral therapy to one of four treatment groups in a 2 x 2 factorial design: 1) three adherence counseling sessions within one month of therapy initiation, or 2) a visual and audible alarm device, programmed by staff, to carry at all times during six months, or 3) both adherence counseling and the alarm device, or 4) neither counseling nor the alarm device (control). Counseling sessions, which followed a written standardized protocol and lasted between 30 and 45 minutes, had no significant effect on the proportion of participants who achieved adherence ≥ 80% or ≥ 95%, as determined using low risk of bias pill counts at pharmacy refill visits, but resulted in a lower hazard rate of viral failure. The authors hypothesized that the clinical benefit of counseling could relate to providing the sessions in advance of, and just after, therapy initiation. The alarm device did not improve the adherence or viral outcomes.
Haynes 1976 randomly allocated, through the minimization method, 38 patients who were both hypertensive and non‐adherent (less than 80% of prescribed pills) at the end of a six‐month trial to an intensive adherence intervention or control. The intervention included care provided at the work site, special pill containers, counseling, reminders, self monitoring of adherence and blood pressure, support groups, feedback and reinforcement for adequate adherence and blood pressure‐lowering, all administered with bi‐weekly contacts by a lay program co‐ordinator who was supported from study funds. At six months follow‐up, there was a significantly higher adherence in the intervention group, as measured by low risk of bias unobtrusive home pill count. The change in diastolic blood pressure after six months was not statistically significantly different between groups (difference in change 3.5 mm Hg; P value = 0.12), although the small sample size might have meant insufficient power to detect a clinically meaningful difference. The authors discussed the possibility that simply the increased attention for intervention patients could have contributed to the improved adherence, rather than the specific intervention components. It has to be noted that medical therapy for intervention patients was more often intensified at the end of the study, while the intervention co‐ordinator was not allowed to contact treating physicians.
Ellis 2012 tested whether an average of 5.6 months of multi‐systemic therapy (MST), a highly intensive, home‐based, tailored family intervention, improved treatment adherence and HbA1c levels compared with weekly phone support during 4.9 months, among 146 poorly controlled adolescent diabetics (mean HbA1c = 11.7%, where good control would be an A1c of 7% for most patients). In MST, therapists were expected to meet with families, their related contacts (e.g. extended family, physicians, and school personnel), or both, a minimum of two times per week at the beginning of treatment with an option for a reduced number of sessions at the end of treatment based on family progress toward treatment goals. Treatment was planned to last for approximately six months. All participants in the trial received standard medical care in addition to MST or telephone support. At seven and 12 months follow‐up, the intervention lowered HbA1c and improved adherence (Diabetes Management Scale) as reported by the parent, but not as reported by the adolescent. As the authors acknowledged, it has to be evaluated whether such an intensive intervention is cost‐effective, especially as the difference in improvements in HbA1c were relatively small (e.g. A1c ‐0.74%, 95% confidence interval (CI) ‐1.48% to ‐0.01%, at 12 months) in view of the poor control at baseline (A1c 11.7%).
Farooq 2011 randomized 110 patients with schizophrenia or schizoaffective disorder to receive family supervised treatment (STOPS) or care as usual. In addition to usual care, participants in the STOPS arm each had a key care supervisor, defined as any family member living with the individual for at least six months and providing support for the treatment as identified by the participant. Education was provided to the key care supervisor about the nature of the illness, misconceptions about treatment, the relationship between supernatural and biological causes of illness (some people believing in supernatural causes might think they cannot do anything about the disease), and the importance of continuing the medication, as well as basic skills in how to administer and supervise the medication. It was emphasized that participants should not be antagonized and violence should never be used in case of refusal to accept the treatment. Steps involved in collecting medicine from the treatment center, storage at home, administering tablets and their ingestion by the participant and how to confirm this were demonstrated. Intervention participants also received free medicines while control group members were left to their own means to obtain their medications. The proportion of patients with perfect adherence, as measured by a five‐point self report scale supplemented by pill count data, was higher at three and 12 months in the intervention group, but not at six months. Supervised therapy also improved symptoms as measured by the Global Assessment of Functioning Scale and Positive And Negative Syndrome Scale. However, it was unclear to what extent free provision of medication in the intervention group for the study contributed to the effect, since control patients could only apply for free drugs through a regular care process (not for the study), if eligible.
Morgado 2011 randomized 197 patients with arterial hypertension, who had been on antihypertensive therapy for at least six months, to receive either counseling from a hospital pharmacist at a specialized outpatient clinic, or regular care at a traditional hospital clinic without a hospital pharmacist. Hospital pharmacists interviewed patients, assessed problems with blood pressure control, educated patients, advised physicians on medication changes, and provided intervention patients with written educational material. Patients in the intervention group were also encouraged to bring all empty blisters and boxes of antihypertensive medication to clinic visits for recycling and to verify compliance with therapy. The intervention improved the primary outcome of proportion of patients with blood pressure controlled to target, and reduced the proportion of patients with low medication adherence as measured by a five‐item questionnaire. The medical therapy advice from pharmacists to physicians might have contributed to the improved blood pressure control in addition to the improved adherence, although the authors report that there were no marked differences compared with the control group regarding therapy changes.
Lester 2010 randomized 538 patients newly initiating antiretroviral therapy, and who had access to a mobile phone and, if required, a partner able to read educational materials, to receive interactive short message service (SMS) or care as usual. Patients in the intervention group received a short education session on the intervention from clinicians, received an SMS every Monday asking "How are you?", and were required to respond within 48 hours to indicate that everything was fine or they had a problem. In case of no response within 48 hours or an indicated problem, the clinician called the patient. The intervention was based on existing mobile phone services and SMS messages were sent by available nurses or clinical officers; no personnel or SMS credits were provided specifically for the study. In the intention‐to‐treat analysis, the intervention improved the proportion of patients with self reported adherence greater than 95% as well as viral suppression (HIV‐1 RNA < 400 copies/ml). Of note, the intervention was reported to function well during a period of political turmoil and population displacement, directing patients to alternative health resources using interactive SMS.
Martins 2009 randomized 270 patients with pulmonary tuberculosis from urban community clinics in Timor‐Leste, which had a well‐functioning tuberculosis treatment program including direct observation of medication taking, to receive the intervention with supplementary food or nutritional advice only. Intervention patients were required to attend the clinic daily for routine tuberculosis treatment, and additionally were offered nutritious daily meals at the clinic during the first eight weeks with direct observation of consumption by clinic personnel, and received daily meal packages to take home during weeks 9 to 32. Control group patients were also required to attend the clinic daily for routine care, and additionally received advice regarding a nutritious diet, but did not receive food. The intervention did not improve the primary outcome of proportion of patients completing treatment (sputum clearance) or completion of eight months of treatment, nor did it improve medication adherence or clinical symptoms including cough. The significant weight gain in the intervention group could be beneficial for the tuberculosis patient group, but was not achieved through better medication adherence and therefore not pertinent to the research question of this review. Of note, a civil conflict arose during the last months of the study, which caused displacement of a large population and complicated adequate completion of the study.
Simoni 2009 randomized 226 HIV‐positive patients initiating or switching to a new antiretroviral medication in a factorial design to either peer support, pager messaging, both peer support and paper messaging, or care as usual only. Regarding peer support, clinic staff selected peer supporters who were also HIV patients on antiretroviral therapy, and had a high therapy adherence, regularly attended clinic visits, were socially skilled, and were able to participate in training and supervision. Peers were, as much as possible, matched to participants based on race/ethnicity, sex, and sexual orientation. During three months, aiming to use twice‐monthly group meetings and thrice‐weekly phone calls, peer supporters addressed barriers to medication adherence and potential solutions. Patients could choose to continue attending meetings and seeking assistance after three months. The three months pager intervention involved automated individually tailored interactive messaging, addressing medication adherence, education, entertainment, and adherence measurement. Messaging frequency could be tailored to the patient's preference with a minimum of three daily messages in the first two months, which was tapered in the third month. At three months, the only significant effect was for self reported adherence in the peer support group, compared with care as usual. No effects were found of either peer support or the pager intervention on self reported adherence, electronically monitored adherence, and viral load and CD4 count as reported in routine medical charts, at six and nine months. The one significant effect was likely a chance finding, considering the testing of multiple outcomes at different time points and the absence of confirmation by Medication Event Monitoring System (MEMS). The authors discussed that the lack of an effect could be related to the poor use of the intervention by participants, the high quality of usual care in this HIV‐specialized clinic, and the inclusion of all patients on therapy rather than those with adherence problems only.
Simoni 2007 randomized 136 HIV‐positive patients with prescribed antiretroviral therapy to receive a peer‐led social support intervention or standard care. The three months peer support intervention was of similar design to the intervention for Simoni 2009, with the difference that in the present study patients could not choose to continue attending meetings and seeking assistance after three months. The intervention did not improve adherence as measured by self report and MEMS, nor did it lower HIV‐1 RNA viral load values as routinely reported in medical charts, at three and six months follow‐up. The authors discussed the possibility that the lack of an effect could relate to the poor use of the intervention by participants due to multiple barriers—including poverty, substance abuse, and insufficient time to establish trust between patient and peer supporter—limiting consistent attendance at meetings and receiving phone calls for adherence.
Wu 2006 tested the effect on adherence and mortality of pharmacist phone counseling, addressing medication adherence, lifestyle, and the next follow‐up visit, versus usual care, among non‐adherent stable patients on five or more chronic medications. Of 442 randomized patients, 236 had become adherent since screening. Adherence was measured by pharmacists using a structured questionnaire in combination with medication dispensing information: taking 80% to 120% of prescribed pills was considered adherent. A proportion of all medications for which the patient was adherent was calculated, but it was unclear how this was used since the authors only distinguished adherent and non‐adherent. After receiving six to eight pharmacist calls during two years, the intervention group had fewer baseline non‐adherent patients who remained non‐adherent, and more baseline adherent patients who remained adherent. The phone counseling intervention also reduced the risk of all‐cause mortality from 18% to 11% (relative risk 0.59, 95% CI 0.35 to 0.97; P value = 0.039). Considering that mortality is hard to improve solely with an adherence intervention, and the confidence interval for the relative risk is wide, this result needs to be replicated.
Weber 2004 randomized 60 HIV patients, who were stable on a combination of at least three antiretroviral medications and had a viral load of less than 50 copies/ml, to a cognitive behavioral intervention or standard care. Patients in the intervention group were given contact information for a psychotherapist, and asked to schedule a first appointment. The psychotherapist and patient determined a visit schedule for the year, with a minimum of two sessions and maximum of 25 (median was 11). In addition, they would identify at least two treatment goals, of which medication adherence was one, which would be targeted with treatment based on cognitive behavioral therapy principles. The proportion of patients with adherence of 95% or greater as measured by MEMS, and self reported adherence as measured on a visual analog scale, was higher in the intervention group at 10 to 12 months, but the regression coefficients for change in MEMS adherence during the study were not different between intervention and control. Viral load and CD4 count were not different between groups, but the intervention group showed an improvement in mental state, as measured by a standardized questionnaire on experience and behavior. This study was designed as a feasibility study, with no reported sample size calculation, and it is unclear to what extent the study was powered to detect differences in clinical outcomes, or if significant effects would remain after correction for multiple comparisons.
Laporte 2003 randomized 86 patients who were hospitalized for a thromboembolic disease and needed oral anticoagulation for at least three months, to either intensive education or standard education on anticoagulation. Patients in the intervention group received visual educational material, daily visits from healthcare providers, and daily tests on their education for the duration of the hospitalization, all aimed at the importance of medication adherence and causes of anticoagulation instability. Control group patients received standard education without any of these features for the entire duration of hospitalization. Following discharge, no differences were found regarding correct bottle openings, timing of bottle openings or pill count, all measured using MEMS. In addition, no differences were found regarding the clinical effect of anticoagulants, e.g. proportion of values or the proportion of days the INR (international normalized ratio) values were within the therapeutic target range. The study used a factorial design and also randomized patients to anticoagulation with either warfarin or acenocoumarol, but these medication groups did not differ regarding adherence and no statistical interaction was found between the medication and educational interventions.
Stevens 2002 randomized 335 patients with dyspepsia and confirmed Helicobacter pylori infection, who were prescribed seven‐day treatment with omeprazole, bismuth subsalicylate, metronidazole, and tetracycline hydrochloride, to either an intensive pharmacist counseling intervention or regular pharmacist counseling. Intervention patients received a detailed 15‐minute pharmacist counseling session at the start of therapy, addressing side effects, the importance of completing therapy, potential barriers and coping strategies related to adherence, and encouragement to call the pharmacist in case of problems, as well as a standard phone call by the pharmacist after two to three days. Patients in the control group received a standard five‐minute pharmacist counseling session at therapy initiation, describing the proper protocol to take the medication and providing an opportunity to ask questions. Self reported medication adherence and Helicobacter pylori eradication rate, as measured by carbon14 urea breath test, were not different between the intervention and control groups at three months. The authors indicated that the lack of an effect could relate to enrolment of motivated patients who were doing well at baseline, the use of daily blister packs in all patients, which might have enhanced adherence, or spill‐over of the intervention to the control group due to the same pharmacists applying the two treatments, both of which included counseling.
Nazareth 2001 randomized 362 hospitalized patients over 75 years, who were taking more than four medications at discharge, to either an intensive or a standard pharmacist discharge plan. Patients in the intervention group received an assessment by a hospital pharmacist, who evaluated therapy appropriateness and the patient's ability to manage the medications, and educated patients on appropriate adherence and how to liaise with important healthcare providers. An individualized discharge plan was devised containing the patient's medications and required adherence support, and copies were given to the patient and an assigned community pharmacist, family physician and other involved providers. After 7 to 14 days the community pharmacist visited the patient at home to reassess therapy adherence and barriers, and intervene and schedule additional follow‐up visits as deemed appropriate. Control group patients received standard discharge procedures by a hospital pharmacist, including a letter to the family physician. No differences were found at three and six months for hospital readmission, death, outpatient clinic visits, and family physician visits, nor for self reported measures including general well‐being, satisfaction, adherence, medication knowledge, and medication hoarding. This study included old and high‐risk patients, of whom 11% had a Mini‐Mental State Examination score of 15 or less at baseline and 15% died during six months, leaving 74% of participants for interview on self reported measures at six months.
Walley 2001 tested the effect of direct observation of therapy, and randomized 497 new sputum‐positive tuberculosis patients to one of three arms: 1) direct observation by health workers six days per week during two months, 2) direct observation by family members, 3) self administered therapy, obtained by bi‐weekly visits to a health facility. At seven to eight months, both direct observation intervention groups had comparable rates to the control group for the outcomes of cure (sputum‐negative on two most recent occasions) and cure or treatment completion (no smear results on at least two occasions, but treatment completed). The authors indicated that the lack of an effect might be due to challenges such as the high rate of patients not being able to comply with direct observation of therapy by health workers, and the implementation of interventions for this study on top of a recently strengthened tuberculosis care system.
Discussion
Summary of main results
The current review updated our 2008 version, Haynes 2008, with 109 new RCTs, a substantially larger number than expected from previous publication rates. To our knowledge this is the only comprehensive (not restricted to specific settings, medications, or diseases) systematic review of interventions to improve medication adherence based on randomized controlled trials (RCTs) that assessed both adherence and clinical outcomes. Despite the more than two‐fold increase in the knowledge base, the interventions and findings of these RCTs only slightly alter the conclusions of the previous version of our review. Compared with the previous update, we now: 1) report a lack of convincing evidence among studies with the lowest risk of bias; 2) no longer try to classify studies according to intervention type; 3) make our database available for collaboration on sub‐analyses. The wide variety of settings, participants, intervention types, medications, adherence measures, and clinical outcomes precluded summarizing findings to reach reliable general conclusions. RCTs included in the current review reported effects that were inconsistent from study to study. A minority of lowest risk of bias RCTs reported improving both adherence and clinical outcome, but these typically had very complex interventions that would be difficult to implement in usual practice setting. Thus, as a qualitative generalization, methods of improving medication adherence for chronic health problems tested to date are mostly complex and not very effective, so that the full benefits of treatment cannot be realized. Therefore, the quest for effective and practical interventions to promote medication adherence and improve clinical outcomes must continue. In acknowledgement of the need for collective advancement, we make our database available for collaboration on sub‐analyses.
To the extent that they represent true innovation, the increase of trials is most encouraging. Even when outcomes were improved, however, the effects were generally small. Effects were seldom assessed on major clinical events such as death or hospitalization, and when done these were rarely significant, albeit possibly due to insufficient study power. The diversity, complexity, and uncertain effects of the interventions, as well as the often uncertain risk of bias for blinding treatment allocation and outcomes assessment, make generalizations about which interventions work and which do not problematic.
Quality of the evidence
Our narrative focused on the RCTs with the lowest risk of bias, to provide a reasonable sampling of the details and diversity of included trials. We identified only 17 studies as having a low risk of bias for study design and clinical outcome assessment. Their interventions were generally complex, trying to overcome multiple barriers to adherence by several means of tailored ongoing support. The lowest risk of bias RCTs primarily involved enhanced support from family, peers, or allied health professionals such as pharmacists, who often delivered intense education, counseling (including motivational interviewing or cognitive behavioral therapy by professionals), and/or daily treatment support. Of these RCTs, five improved both adherence and clinical outcomes, three improved only adherence outcomes, one improved only clinical outcomes, and eight did not improve adherence or clinical outcomes. This was a similar success rate to that found in the 21 newly included studies in the 2008 update (Haynes 2008). Whether these numbers reflect the actual proportion of studies that had an important effect is uncertain, and simple 'vote counting' is not informative because:
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a large variety of often complex interventions would be inappropriately treated as equal;
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many studies tested multiple outcomes without statistical correction, thereby increasing the risk of false positives findings;
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many studies were underpowered thereby potentially hiding a true effect;
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most outcomes were surrogate measures (e.g. blood pressure) rather than patient‐important outcomes.
No common intervention characteristics for success were apparent among these studies. Therefore, even in the studies with the strongest methodology, no consistent evidence exists that medication adherence can be improved within the resources usually available in clinical settings, and that this will predictably lead to important improvements in treatment outcomes. The results might have been different with more relaxed criteria for participant loss to follow‐up, but this would further muddy the water with even lower‐quality RCTs, and we prefer to stand by our criteria of at least 80% follow‐up in all treatment groups. In addition, most studies enrolled patients who were willing to participate, rather than those that had low adherence. This makes it harder to show an effect, as opposed to applying the intervention only to those in need of adherence support. Although we were not able to assess potential publication bias, as we did not pool results, we estimate that some publication bias is likely due to the widespread lack of power to pick up potentially meaningful effects. If so, our low estimate of the benefits of interventions to date would likely only be reinforced by unpublished studies.
Interventions
New developments
Since the last update, some new or little studied intervention types have been reported. Although the technologies have been around for a while, we were now able to include several RCTs testing the effect of mobile text messages (Simoni 2009; Hou 2010; Lester 2010; Boker 2012; Zolfaghari 2012), and remote internet‐based treatment support (Chan 2007; van der Meer 2009). Of the five RCTs testing the effect of mobile text messages, two were included in the lowest risk of bias group. Only Lester 2010 showed a significant effect, on antiretroviral therapy adherence and the clinical outcome of viral load in HIV patients. There may be potential to build on the opportunities provided by text messaging, including in low‐resource settings. Simoni 2009 also targeted HIV patients, but did not show an effect of pager messages on adherence or viral load. The remaining three RCTs testing mobile text messages for oral contraceptives, acne therapy, and diabetes were not included in the lowest risk of bias group, and none had an effect on both adherence and the clinical outcome (Hou 2010; Boker 2012; Zolfaghari 2012). Further, Chan 2007, a study not included in the lowest risk of bias group, tested internet‐based asthma telemonitoring for patients of 6 to 17 years, but found no effect on adherence or clinical outcomes. van der Meer 2009 tested internet‐based asthma self management plus education among adults, whereby communication could also be done using mobile text messaging if preferred, and found no improvement in medication adherence, only moderate improvements in asthma control and lung function, and no clinically significant improvements in asthma‐related quality of life and exacerbations. Further, no other RCTs testing the effect of internet‐based disease telemonitoring made it through our selection process. Although both technologies have great potential to reach large population groups to improve adherence, further rigorous testing is necessary. Ongoing studies might strengthen the knowledge base and provide more details on how they could be better utilized. The present examples overall do not change our conclusion from the previous update that adherence research is lagging behind the rapid developments in technology, and that research methodology and evidence on their optimal use remain weak.
Allied healthcare providers such as nurses and pharmacists are increasingly delivering part of, or the entire intervention. In our previous update we advised further exploration of their role, and hypothesized that if their roles can be expanded to include counseling patients to enhance medication adherence, this may be feasible in practice. Considering that physicians have limited time, and sometimes skills, to counsel patients on medication adherence repeatedly, shifting these tasks to allied providers seems reasonable and potentially cost‐effective. Several complex interventions involving allied providers were effective, but since they were often only part of the intervention and delivered a variety of intervention enhancing services, their efficacy has to be determined for specific roles and tasks. In addition to the role of allied health professionals, several studies tested family/social interventions, lay health mentoring, or group meetings. It seems worthwhile to explore further involving non‐professional personnel, since the patient's social context is important to optimize chronic care, and might improve cost‐effectiveness.
As mentioned, complex interventions were often used in the new RCTs, typically involving intensive ongoing allied health care provider and social support, sometimes facilitating transitions in care. This seems logical considering that adherence is generally a complicated matter caused by multi‐factorial barriers (ABC Project Team 2012; Kardas 2013), but also raises three primary concerns:
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complex interventions are usually compared with care as usual, while it remains to be seen if they are more effective than a simple intervention;
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if effective, the entire complex intervention should be implementable in other settings, without requirement of excessive additional personnel and costs (implementation flexibility and external validity); and
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if the latter is not feasible, the effects of individual components should be teased out, such as by a factorial design, in order to be able to determine if all components were required or to select the most effective ones.
Related to complexity, many RCTs used personnel and resources supported by research funds. For example, pharmacists would be specifically allocated to the intervention and reimbursed accordingly, but outside this research setting they might not be able or willing to dedicate this time to the intervention. Even if a small effect on clinical outcomes was observed, it remains to be seen whether such interventions can be translated to other settings in a cost‐effective manner. Regarding this, few adequate full cost‐effectiveness evaluations of adherence RCTs are being published (Oberje 2013). These will be needed if clinically important effects are documented.
Process evaluation of an effective complex intervention can be very useful to hypothesize which components were most effective and to identify individual or contextual barriers and facilitators to adherence (Craig 2008). However, we believe that this eventually requires direct comparison in an RCT, compared with usual care or a simple intervention. Two RCTs in the lowest risk of bias group, Simoni 2009 and Chung 2011, applied two different adherence interventions in a factorial design. This design allows testing of the separate effects of multiple intervention components, while also observing their additive effect. This will better inform which components are independently effective, or whether an effect is due to the combination of two components that individually might not be (very) effective. It has to be noted that to be able to test several components and their interactions with sufficient power, the required sample size has to be increased accordingly (McAlister 2003).
Of note, the European Ascertaining Barriers for Compliance project published its final report in 2013 (Demonceau 2013), which also included a comprehensive systematic review including intervention RCTs assessing adherence outcome by means of electronically compiled measures. The authors used a taxonomy to label intervention components and tried to tease out the effect of each component, although they acknowledged that many interventions were complex, highly variable, and not easily summarized. Of the 65 included RCTs, 32 also assessed clinical outcome, with only four showing an effect on clinical outcome.
Promising interventions not included in our review
There are likely many potential areas for which interventions are either in development or lacked high‐quality RCT evidence with adherence and clinical outcomes at the time of our search. We will illustrate this with a selected example regarding cardiovascular prevention single‐pill combination therapies, also since a recent Cochrane systematic review by Ryan et al showed promise for simplified dosing (Ryan 2014). Several of these combination pills, containing multiple proven cardiovascular medications, have already been developed and tested versus the same medications as individual therapies (Working Group on the Summit of Combination Therapy). These pills simplify therapy to only one pill per day, where most cardiovascular patients currently have to take at least four to five separate pills daily. The RCTs testing combination pills typically assessed effects on therapy persistence (e.g. not explicitly discontinuing), rather than daily pill adherence while still on medications, in addition to intermediate clinical outcomes such as blood pressure. However, an RCT published after our search showed that self reported adherence as well as intermediate clinical outcomes (blood pressure, lipid levels) were somewhat improved with a cardiovascular combination pill (Thom 2013). That said, medication was provided free to the combination pill intervention group, while control group participants had to fend for themselves in acquiring their medications (almost half lacked insurance coverage), leaving uncertainty as to whether the improved adherence was due to simplified therapy or facilitated access to medication and cost‐lowering. This study would be a candidate to make it into our next update, but the provision of polypills free of charge constitutes a more complex intervention than the authors highlighted. As a related example, in our previous review we indicated that there is some evidence that a dose frequency of one to two times per day may be associated with better adherence than three to four times per day, and advised better exploration of this dose frequency. None of the new RCTs with the lowest risk of bias addressed this issue, and we would like to highlight this important issue.
Measuring adherence and clinical outcomes
To determine applicability to patient care, we only selected studies that measured both adherence and treatment outcome. This requirement has received the criticism that this resulted in a more negative message than some would like to see. It has been suggested that the findings would be more upbeat and positive if we included studies that measured only adherence. This criticism does not pertain to the purpose of this review, that is, to determine whether adherence interventions make a difference to clinical outcomes. It simply cannot be assumed that measures to increase adherence do more good than harm, even if they increase adherence. Nevertheless, we do agree that investigators who seek to advance the methods for enhancing adherence may find promising leads from studies that do not meet our criteria for measurement of both adherence and clinical outcomes.
Attempts to increase adherence can have adverse effects (loss of privacy and autonomy, increased adverse effects of treatments) (Simpson 2006), and so on. Few RCTs assessed such potential adverse effects. Further, many interventions with an effect on adherence and surrogate clinical outcomes measured relatively short‐term outcomes, typically at 6 to 12 months, which does not mean that their effect would be sustained or that they would lead to important clinical outcomes in the long run.
Adherence measures
A well‐known problem with adherence studies is the inability to measure adherence accurately and reliably, making it harder to pick up true differences, which could have contributed to the variable effects we observed among RCTs. Most studies used patient self report measures, which are known to overestimate adherence (Gordis 1979; Haynes 1980; Stephenson 1993); these studies are at especially high risk of bias when the patient is not blinded to the treatment allocation, which is usually the case. Some validated questionnaires are available, and should be used as much as possible if self report is chosen, but their accuracy and reliability are often limited and depend on the context they are used in.
Increasingly, studies are using Medication Event Monitoring System (MEMS) pill bottle caps. These caps contain a microchip that measures the date and time at which the bottles are opened, but do not register if the patient actually took the medication on those occasions. Although this method is more objective than self report, it could also function as an intervention (patients feel monitored) (Christensen 2009), and increase adherence in both groups, thus diminishing or concealing a true difference. It can also be 'gamed' by the patient who is aware of the MEMS function and wishes to keep non‐adherence private.
A potentially more objective measure that was used in some studies was pill count, which is especially appealing if it is done unannounced, at home, and in an unobtrusive way, in order to prevent patient awareness and anticipation of pill count. However, most pill counts are done on containers that the patient brings with them to a visit to a health professional, and in this circumstance counts can clearly be altered by the patient.
A method that was regularly used, and that probably has the highest likelihood of maintaining blinding of patients and providers, was the use of routine pharmacy refill records. Although this method depends on the assumption that the patient is actually consuming the medication, and the only one doing so, it better allows adequate blinding of outcome assessors. In our view, using more objective measures such as pharmacy records is a productive step forward in the field of adherence research, as it will lead to further valid and reliable results. With electronic records available in most pharmacies, this option is increasingly available, inexpensive, and acceptable, providing that patient consent is obtained.
It is important to note that our review may miss the most severe form of non‐adherence, among those who do not attend for needed care or enter trials. Patients dropping out of care are unlikely to be receiving any medication, and if those in care average about 50% adherence, keeping patients in care is arguably the most important adherence intervention at present. The same rationale can be used for keeping patients on medication, even if they do not attend clinic visits. Both assume, however, that for those who are prevented from dropping out or discontinuing medication, or who are returned to care or restart medication by intervention, adherence rates are sufficient to achieve clinically important benefits. This merits further testing.
Clinical outcomes
Consistent with the large variety in diseases and medications, many different clinical outcomes were reported. Most RCTs measured intermediate biological outcomes, such as blood pressure, serum cholesterol or HIV‐1 RNA, or patient‐reported outcomes such as quality of life, knowledge, beliefs, or attitudes. Very few studies examined major, patient‐important, clinical endpoints such as death or hospitalization. The latter have the lowest risk of bias, as they are obvious and can easily be verified. Intermediate biological outcomes also often have a low risk of bias, although this could be compromised if measurement methods differ among subjects, and outcome assessors are not blinded. For example, measuring blood pressure requires a protocol whereby a fixed number of measurements are taken according to a standardized process, and a provider who is aware of a participant being in the intervention group might (subconsciously or otherwise) alter this process or interpret readings differently. Self reported outcomes such as symptoms and quality of life are more prone to bias, even if using well‐validated general and disease‐specific tools to assess them. Finally, many studies reported self reported knowledge, beliefs, and attitudes, often in addition to more objective clinical outcomes. Although these types of outcomes can be used to further clarify mechanisms of effects, they are often not validated or inadequately validated, are prone to self report or observer bias, and their measurement varies with time and clinical care experiences which limits their reliability.
Study power
Many RCTs had inadequate power to detect a meaningful difference in adherence, and this did not seem to be improved among newly identified RCTs. As a general guide, studies with a single intervention group and control group would need to include at least 60 participants per group if they are to have at least 80% power to detect an absolute difference of 25% in the proportion of patients judged to have adequate adherence. According to this rule, the new RCTs were as likely to be underpowered (40% (44/109)) as RCTs in the previous update, and even among the 17 lowest risk of bias RCTs in the present update, four had insufficient power (Haynes 1976; Laporte 2003; Weber 2004; Farooq 2011). For example, in a study of 38 patients (Haynes 1976), there was a significant increase in adherence associated with the intervention and an interesting within‐group reduction of blood pressure within the intervention group. However, the difference between the intervention and control groups for blood pressure change was not statistically significant. Underpowered studies are more likely to miss a meaningful difference in adherence, even when improving adherence substantially, and showing an effect on clinical outcomes is likely even harder. This is especially true for major events. If RCTs with hundreds or thousands of participants are needed to show that the medication has an effect on major outcomes compared with usual care, it is unlikely that improving adherence among patients who are prescribed the medication will have a substantial effect on major outcomes in a small sample size.
Quality of reporting
Many articles did not provide sufficient detail to allow the risk of bias to be determined, or for the exact nature of what the study tested to be understood. In particular, details of the methods of random sequence generation, concealment of treatment allocation, and blinding of the outcome assessors as relevant for the outcomes were often not reported, and therefore we could not determine the risk of bias. As a consequence, it is possible that some of RCTs that we excluded from our narrative actually had a low risk of bias, but we were unable to determine this based on the manuscript, supplements, and (absence of) author response. The importance of adequate reporting is further illustrated by the initially included RCTs that were eventually discarded due to less than 80% follow‐up after repeated detailed review. The way these studies were reported was sometimes confusing for something as simple as follow‐up rate, and the full picture was only revealed after reading all the details, tables, figures, or supplements. Examples appear in the listing of studies excluded for cause in this review.
Treatment arms, both intervention and control, were also not always described in sufficient detail. For example, while the report might state clearly that patients received reminders, the method of administering the reminder program might not be described, or might be described in some part of the text other than the section on the intervention. Most studies paid research staff to administer interventions, raising issues in generalizability to usual practice settings. This also raised the issue of attribution in many studies: if the control group received 'usual care', there would be no 'attention control' in the study and any effects observed could be due to either the intervention proper or simply the non‐specific effects of increased attention paid to the intervention group. Furthermore, some studies reported that the patients in the control group received 'usual care', but did not describe what that encompassed. If the standard medical care is already performing relatively well, it will be harder to show an improvement with the intervention. Therefore, to understand the trial results better, it is recommended to provide sufficient details on the intervention design and delivery, the assumed change process the intervention aims to deliver, and the care process for the control group, whether this was an active control or usual care (Michie 2009).
Potential biases in the review process
Missed studies
Despite extensive searching, we may have missed some trials that met all of our criteria. The literature on patient adherence is not well indexed because the number of studies is quite small relative to the literature published on other topics, and because it is spread across traditional disease boundaries. We invite readers to send us any studies, published or unpublished, which may meet our criteria.
Study eligibility criteria and 'Risk of bias' assessment
We chose our eligibility criteria to summarize the current best evidence of unconfounded RCTs, with adequate follow‐up completion in all treatment groups, assessing the effect on both adherence and clinical outcome. With other eligibility criteria, such as allowing a larger loss to follow‐up or not requiring clinical outcome, the review results might have been different. In addition, in the absence of clear study details, we could have made judgment calls in our 'Risk of bias' assessment to avoid too many 'uncertain risk' assignments. This might have resulted in more studies being considered 'low risk', and therefore eligible for discussion in our main text. However, we anticipate that the quality of evidence in these trials would be even lower than the moderate study quality which was found in both the overall review and among the RCTs with the lowest risk of bias, and would lead us further from an accurate overview of the current best evidence in a field with a large number of small and low quality studies.
Other reviews
Our review is restricted to prescribed medications, excluding those prescribed for addiction, and to studies that assessed both adherence and treatment outcomes. There are many other systematic reviews of adherence interventions, too numerous to list, especially for specific clinical conditions, and also for non‐medication interventions (e.g. diet, exercise, addictions, and so on). We acknowledge that systematic reviews focusing on specific clinical conditions, medications, or intervention types might draw different conclusions. We chose to focus on all RCTs testing adherence interventions for any self administered therapy, to get a complete overview of the field and to account for the fact that adherence problems are often comparable for different medications. This resulted in the inclusion of a large variety of heterogeneous RCTs that could not reliably be pooled, but we encourage reviewers and researchers who find a signal for effective interventions for a specific condition or medication to share their findings with us and other reviewers. In addition, we invite reviewers interested in specific conditions, medications, or interventions to propose such a specific analysis in our comprehensive database.
Sharing of review data
As indicated, we did not feel it scientifically justified to summarize data across studies, but provided all the details on included RCTs in the tables, as well as a narrative of the RCTs with the lowest risk of bias. For this review we collected a wealth of information, and we invite readers to propose specific analyses of interest. Access to our database for additional analyses will be considered, based on requests to the corresponding author. Please e‐mail your analysis proposal to [email protected].
'Risk of bias' summary: review authors' judgments about each risk of bias item for each included study.
| Study | Clinical problem | Intervention | Control | Effect on adherence (Yes means a statistically significant effect in favor of the intervention; No means no effect or a negative effect) | Effect on clinical outcome (Yes means a statistically significant effect in favor of the intervention; No means no effect or a negative effect) |
| Abrahams 2010 | Post‐exposure prophylaxis for HIV | TELEPHONE COUNSELING: Patients in the intervention group received standard care and telephone counseling sessions. The telephone counseling included 4 calls in the first week, 3 calls in the second and third week, and 2 calls in the last week, but more were made if necessary. The support included the application of basic counseling skills including listening and validating the traumatic events, encouraging participants to take their medication, to seek support from family and friends, to attend formal counseling services, to read the pamphlet, use the diary, and return to the clinic for follow‐up medication | STANDARD CARE: Standard care consisted of psychological containment, medical examination and collection of forensic evidence; HIV testing with pre‐ and post‐test counseling; providing emergency contraception, treatment of sexually transmitted infections and PEP for HIV. Follow‐up was arranged to collect further HIV PEP medication. All patients had an interactive information session to explain the content of the pamphlet, answer questions and demonstrate initiation of the use of the medication diary. The pamphlet contained specific information about taking PEP after a sexual assault; a diary for the 28‐day period on which pill taking was to be marked and contact information on support services. No further contact was made with participants in the control group until the final interview, but they continued to receive standard care from the service | No for improving adherence to prophylactic HIV treatment | No for depressive symptoms |
| Ahmadipour 2010 | Type 2 diabetes | DIARY CHECKLIST: The intervention group was asked to complete a diary checklist about how they took their drugs during the study period.The duration was 12 weeks | COLLECTION OF MEDICATION SHELLS: The control group patients were asked to collect the shells of oral hypoglycemic agents after taking in a pocket. Duration was 12 weeks. | Yes for improving medication adherence in patients with type 2 diabetes with a diary check list intervention | No for improvement in HbA1c levels |
| Al Mazroui 2009 | Type 2 diabetes mellitus | PHARMACIST CARE INTERVENTION: For all patients randomized to the intervention group, the research pharmacist had discussions with their physicians regarding drug therapy and, if necessary, treatment modification was recommended, e.g. more intensive management of hypertension or simplification of dosage regimens if deemed appropriate, taking account of the latest American Diabetes Association (ADA) recommendations. Patients who were randomized to the intervention group were educated on their illness and their medication in a structured fashion, including discussion on risk of diabetes complications, proper dosage, side effects and storage of medications, healthy lifestyle and management of diabetes mellitus signs and symptoms through self monitoring. A printed leaflet to assist with the education program was developed and the patient was given a copy to take home. Supplementary leaflets containing information about hypertension and hyperlipidemia were also given to the patients if they suffered from these conditions. The educational advice was reinforced when patients came to the hospital pharmacy to collect their prescribed medicines on their monthly schedule. In addition, behavioral modification aspects of the Pharmacist Care intervention involved advice on the following: self monitoring of glycemic control (patients were encouraged to monitor their blood glucose levels 3 times per day, to record these values and bring a record book to all subsequent appointments); physical exercise (this involved initiation of an exercise plan that could be incorporated into the patient’s daily schedule, after taking into consideration their level of fitness, e.g. 1‐hour walk daily; diet (the patient was assisted with the identification of dietary behavior that adversely influences blood glucose control, lipid levels, weight management, and of the times of day when the patient was most vulnerable to overeating, and given improved understanding of the relative effects of certain food choices on blood glucose control); medication adherence (patients were asked about any problems that they had encountered with regard to taking their medication and were offered education and practical help to encourage them to take the medicines prescribed for them by their physician); and smoking cessation (patients were encouraged to stop smoking by advising them about the danger of smoking to health, with emphasis on the increased dangers of smoking in diabetic patients) | USUAL CARE: Control group participants received normal care from medical and nursing staff. They did not receive any pharmacy clinical service but received advice on self monitoring their blood glucose by medical or nursing staff | Yes for improving adherence to medication at 12 months | Yes for BMI, blood glucose, HbA1c, blood pressure, cholesterol, quality of life, Framingham prediction scores, and British National Formulary risk prediction |
| Al‐Eidan 2002 | Helicobacter pylori | Intervention patients (n = 38) received their medicines via the hospital pharmacy and were counseled (and followed up) by a hospital pharmacist | Control patients (n = 38) were given a standard advice sheet and referred to their GP who prescribed the same therapy | Yes for improving compliance with a 1‐week course of triple therapy to eradicate H. pylori | Yes for improving clinical outcomes for the intervention group who had a significantly higher rate of H. pylori eradication |
| Amado 2011 | Hypertension | INTERVENTION (IG): Patients in the Intervention Group (IG) had 4 visits with specially trained nurses who used standardized guidelines and who had attended a 10‐hour workshop that focused on the antihypertensive medications. Each visit lasted for an average of 15 minutes. Information was personalized to the needs of the patient. Schedule sheets with the treatment plan were provided which contained information on the prescribed drugs and dosage schedule as well as basic advice on how to maximize the treatment schedule. The sheets were provided to reinforce the nurse's verbal instructions | CONTROL GROUP (CG): Control patients received usual clinic care without any standardized intervention | Yes for Haynes‐Sackett test; no for Morisky‐Green test, self declared 3‐month adherence, and pill count | No for systolic and diastolic blood pressure, hypertension control, BMI, and number of antihypertensive drugs taken |
| Anderson 2010 | Schizophrenia | ADHERENCE TREATMENT: The intervention was 'Adherence Therapy' a manualized, patient‐centric approach that seeks to address a broad range of factors known to affect adherence. This individual therapy focuses on the needs, concerns, fears, values, goals, and experiences of the individual with the aim of encouraging people to take their medications. It was delivered by 4 therapists with Master's degree in social work. There were 8 one to one sessions of between 20 to 60 minutes, over 8 weeks. Follow‐up was conducted after the completion of the therapy. All intervention patients also received treatment as usual | TREATMENT AS USUAL: TAU included day treatment, case management, employment placement, medication monitoring, and individual counseling. During the trial, AT participants did not see their own therapist for therapy sessions, but continued their other treatment activities | No for improving adherence to antipsychotic medication in schizophrenia patients receiving adherence therapy and treatment as usual at 8 weeks | No for improving the PANSS positive, negative and general scores in schizophrenia patients receiving adherence therapy and treatment as usual at 8 weeks |
| Andrade 2005 | HIV | Disease Management Assistant System (DMAS) device, programmed with verbal reminder messages and dosing times for medications in the highly active antiretroviral treatment (HAART) regimen with monthly adherence counseling and feedback (see Control; n = 29) | Monthly adherence counseling (education about barriers to adherence, hazards of non‐adherence, their prescribed HAART regimen) and adherence feedback (n = 29) | No for all adherence outcomes | No for CD4+ cell count. Yes for plasma HIV RNA (significant for 2 of 4 measures) |
| Ansah 2001 | Malaria | The use of pre‐packed chloroquine tablets (n = 155) | The use of chloroquine syrup (n = 144) | Yes. The tablet form of medicine resulted in higher adherence rates, but it is not established whether this is due to the formulation or the lack of provision of a standard measuring device | No, there was no difference in the clinical outcomes |
| Antonicelli 2008 | Congestive heart failure | HOME TELEMONITORING: Patients were in a 12‐month follow‐up period. Patients (or one of their relatives) were contacted by telephone at least once a week by the CHF team to obtain information on symptoms and adherence to prescribed treatment, as well as blood pressure, heart rate, bodyweight and 24‐hour urine output data for the previous day. A weekly ECG transmission was also required. Evaluation of these parameters was followed by reassessment of the therapeutic regimen and modification whenever needed. In addition, clinic visits were arranged as required on the basis of the data provided by telemonitoring or telephone interviews. Decisions on hospital re‐admission during follow‐up in both groups were made after consultation with a CHF team member | STANDARD CARE: Patients (or one of their relatives) in the control group were contacted monthly for 12 months of follow‐up by telephone to obtain data on new hospital admissions, cardiovascular complications and death. These patients were also routinely seen in the CHF outpatient clinic every 4 months, with additional visits being arranged whenever changes in clinical status made this necessary | Yes for improving adherence to beta‐blockers, HMG‐CoA reductase inhibitors and aldosterone receptor agonists at 12 months in elderly patients with CHF | Yes for composite endpoint of mortality and hospital readmission, hospital readmission (alone) and heart rate reduction. No for left ventricular ejection fraction change and mortality (alone) |
| Apter 2011 | Asthma | PROBLEM‐SOLVING INTERVENTION: Participants met with a research co‐ordinator for 4 sessions of a problem‐solving (PS)intervention. PS comprised 4 30‐minute sessions. The individualized intervention involved 4 interactive steps, usually 1 per research session. For the 158 participants who reported missing doses of inhaled corticosteroids (ICS), the goal was to improve adherence. For the 7 participants who declared adherence to the prescribed regimen, the goal was to maintain adherence. The first PS step consisted of defining the problem: improving or preserving adherence to ICS use within the patient's unique context and orientation. Problem orientation facilitated the adoption of a rational, positive, and constructive appraisal of how to achieve adherence, with non‐adherence being presented as a problem to be solved. PS was presented as a means of coping with problems more generally and modifying attitudes or beliefs that inhibit or interfere with attempts to solve problems. It was a motivational technique to help the participant view the occurrence of problems as inevitable, normal, and solvable. This first step involved breaking problems into small achievable pieces. The second step was brainstorming for alternative solutions. The third step was choosing the best solution by weighing the consequences, both desirable and undesirable, of each candidate solution. Between the third and 4th meetings, the solution was tried. For the 4th step, the chosen solution was evaluated and revised. As part of this intervention, downloaded data from monitored ICSs were shared with the participant in a nonjudgmental fashion at each visit. At these sessions, subjects followed the same PS steps for addressing an additional problem of their own choosing, such as increasing physical activity. The problems were sometimes interrelated; for example, a father wants to play sports with his child, and improving asthma management makes this easier | ASTHMA EDUCATION: Patients attended 4 30‐minute sessions, conducted by a research co‐ordinator. Each session was about an asthma education (AE) topic unrelated to self management, adherence, or inhaled corticosteroid (ICS) therapy. The topics covered, 1 at each session, were the following: (1) the proper technique for using an albuterol rescue metered‐dose inhaler and a dry powder inhaler or spacer, depending on the patient's medications; (2) the use of peak flow meters; (3) common asthma triggers; and (4) the pathophysiology of asthma. These sessions did not involve discussion of problem‐solving or adherence, only didactic presentation of health information | No for improvement in medication adherence | No for improving asthma control, spirometry, emergency department visits and hospitalizations, and asthma‐related quality of life |
| Bailey 1990 | Asthma | Pamphlet, workbook, counseling, phone follow‐up, support group, and reinforcement of adherence (n = 132) | Instructional pamphlet alone (n = 135) | Yes | Yes |
| Bailey 1999 | Asthma | 2 intervention groups: 1) Asthma Self Management Program (n = 78) ‐ a skill‐oriented self help workbook, which patients were counseled about in a one‐on‐one session and during 2 asthma support group meetings. Patients were also given peak flow meters and trained to use them for early detection of impending asthma attacks. They also received 2 telephone calls and a follow‐up letter at 1, 2, and 4 weeks, after the counseling session. 2) Core‐Elements Program (n = 76) ‐ a revised, shortened workbook that was reviewed in a 15 to 20 minutes one‐to‐one counseling session. Patients were trained to use inhalers and peak flow meters. They also received a follow‐up telephone counseling session a week later and a follow‐up letter 2 weeks later | Usual education from their physician, as well as a standardized set of pamphlets containing information about asthma. No steps were taken to ensure that patients read the pamphlets (n = 78) | No (medication adherence and inhaler use) | No for all clinical outcomes (asthma symptoms, respiratory illness, functional impairment, use of health services |
| Baird 1984 | Hypertension | Once daily metoprolol (n = 196) | Twice daily metoprolol (n = 193) | Yes | No |
| Beaucage 2006 | Acute infections | Pharmacist telephone follow‐up intervention (PTFI; n = 126) | Usual pharmacist intervention (UPI; n = 129) | No | No for all clinical outcomes |
| Becker 1986 | Hypertension | Special "reminder" pill packaging (n = 86) | Separate vials for each medication (n = 85) | No | No |
| Berrien 2004 | HIV | The intervention in intervention group (n = 20) consisted of 8 structured home visits over a 3‐month period by the same home care experienced registered nurse. The visits were designed to improve knowledge and understanding of HIV infection, to identify and resolve real and potential barriers to medication adherence, and ultimately to improve adherence. Spanish‐speaking case managers, incentives, notebooks with stickers and pill‐swallowing training were also part of the home visit training sessions | In the clinic setting for control group (n = 17), the physician, nurse and social worker provided standard medication adherence education at clinic appointments generally scheduled at 3‐month intervals. Phone follow‐ups and a single home visit were planned if the staff felt they were needed. Visual aids for remembering medications, medication boxes, beepers, and general technical and emotional support were regularly offered. The clinic nurse contacted the family by telephone when the patient was starting a new medication, was having difficulty with adherence, or needed clarification and support. A single home visit was planned when and if the clinic staff believed medication adherence was poor despite the implementation of the above listed techniques | Yes for pharmacy report of refill frequency; no for self reported | No |
| Boker 2012 | Mild to moderate acne | TEXT MESSAGE REMINDERS: 20 patients were then randomized to receive daily, customized text‐message reminders at a predetermined time. The website LetterMeLater.com was used to create an automated and customized electronic reminder schedule for each patient in this group at their baseline visit. Individual texting schedules were chosen based on each patient's preference and the anticipated time of each medication use. Once the schedule was created, patients in the reminder group received a customized text message twice daily (morning and evening), reminding them to apply the Duac (Stiefel Laboratories) or Differin (Galderma) gels, respectively. The content of each text message was identical for each patient and varied only by including the recipient's first name at the start of the message. Patients in the reminder group were asked to text back a reply if and when each application was completed in an attempt to compare actual adherence (measured by MEMS caps opening/closing events) and self reported adherence. All medication tubes and their corresponding MEMS caps were clearly labeled to avoid mix‐ups | USUAL CARE: Control group patients received usual care and were not provided with text message reminders. | No for improving adherence to acne medication with daily, customized text messages | No for improvement in acne severity or quality of life with text messages |
| Bond 2007 | Coronary heart disease | MEDICINE MANAGEMENT SERVICE (MEDMAN): The intervention was a comprehensive, community pharmacy‐led medicines management called MEDMAN. This intervention comprised of an initial consultation with a community pharmacist to review the appropriateness of therapy, compliance, lifestyle, social and support issues. Further consultations were provided according to pharmacist‐determined patient need. Recommendations were recorded on a referral form which was sent to the GP, who returned annotated copies to the pharmacists. The intervention lasted 12 months | STANDARD CARE: Control group patients not provided with MEDMAN intervention. Follow‐up data were collected at 12 months by audit clerks and postal questionnaire as at baseline. Intervention patients were also asked about their experience of the medicine management service | No for improving medication compliance in patients with coronary heart disease with a medicines management service | No statistically significant differences were found for any of the (adjusted) main outcome measures between the 2 groups at follow‐up |
| Bonner 2009 | Asthma | INDIVIDUALIZED ASTHMA MANAGEMENT INTERVENTION: Families in the intervention group received asthma education by a trained Family Co‐ordinator who also provided individualized support in helping caregivers monitor their children's asthma using diaries. The Family Co‐ordinator helped caregivers interpret the diaries and communicate the contents to their doctors. 3 group education workshops were held at 1‐month intervals that followed the asthma self regulation model. Families were trained to use the diaries and peak flow meters. Family Co‐ordinators regularly called families to discuss their diary records. The second workshop used patients' diary records as illustrations of the relative effectiveness of controller medicines over rescue/quick‐relief drugs in preventing asthma symptoms over time. Participants reviewed their own records of medicines and symptoms. The third workshop described asthma management as a two‐pronged effort of pharmacotherapy and trigger control. Between the 1st and 2nd workshops, the Family Co‐ordinator prepared families for their doctor visit. The Family Co‐ordinator accompanied families to the doctor visit where he intervened if the family failed to communicate a thorough asthma history. The children in the intervention group were tested for allergies by an attending allergist at the hospital if they had not recently been tested by their own physician. Family Co‐ordinator conducted a home environment assessment and suggested strategies for reducing asthma triggers | USUAL CARE: Control patients (n = 63) received usual medical care at private or hospital‐affiliated community pediatric practice | Yes for family adherence to asthma medicines according to the frequency and dosage as prescribed on the labels and yes for prophylactic use of bronchodilators | Yes for improvements in self efficacy for management of asthma, phase of asthma regulation and symptom persistence |
| Brown 1997a | Hyperlipidemia and coronary artery disease | Controlled release niacin twice daily (n = 31) | Regular niacin 4 times a day (n = 31) | Yes | Yes |
| Brus 1998 | Rheumatoid arthritis (RA) | 6 patient education meetings. The education program focused on compliance with sulphasalazine therapy, physical exercises, endurance activities (walking, swimming, bicycling), advice on energy conservation, and joint protection. 4 (2‐hour) meetings were offered during the first months. Reinforcement meetings were given after 4 and 8 months. The program was implemented in groups and partners were invited to attend the meetings | The control group received a brochure on RA, as provided by the Dutch League against Rheumatism. This brochure gives comprehensive information on medication, physical and occupational therapy (n = 31) | No | No |
| Bruzzese 2011 | Moderate to severe persistent asthma | ASTHMA SELF MANAGEMENT FOR ADOLESCENTS (ASMA): Students in the ASMA group receive an 8‐week intensive program. The intervention consists of 3 45‐ to 60‐minute group sessions, and individual tailored coaching sessions held at least once per week for 5 weeks. Sessions are delivered by trained health educators during the school day. In addition to teaching asthma management skills and ways to cope with asthma, the health educators encourage students to see their medical provider for a clinical evaluation and treatment. The individual sessions reinforce the educational messages taught in the group, help students identify and overcome barriers to managing their asthma, and coach students regarding their medical visits. The health educator offers to accompany the student to the medical visit to provide moral support, coaching, or advocacy when coaching fails. Medical providers received a presentation by experts in person or by telephone about a recommended change in therapy. The medical providers were first mailed a packet containing: a letter informing them that one of their patients was in the study and would be referred to him/her for a clinical evaluation; a blank asthma checklist the students complete throughout the intervention and bring to the visit with the provider; and a blank asthma action plan the provider is asked to complete. Within 2 weeks, a pediatric pulmonologist or adolescent medicine specialist called the students' medical providers to discuss the concepts presented in the program and to answer any questions regarding NHLBI Institute criteria for treating asthma | WAIT LIST CONTROL: The control group were kept on wait list until the completion of 12‐month interviews and then received the ASMA intervention | Yes for improving adherence in adolescents with asthma at 6 months; No for improving adherence in adolescents at 12 months | Yes for reducing night‐time awakenings in previous 2 weeks, and school absence in previous 2 weeks. No for reducing symptom days in prior 2 weeks. No for improving QOL at 6 months. Yes for QOL improvement at 12 months. Yes for reduction in urgent medical care use |
| Burgess 2007 | Asthma | FUNHALER: Patients received a Funhaler for their daily asthma medication. The Funhaler is a small volume spacer that incorporates an incentive toy (spinning disk and whistle) that is driven by the child's expired breath | CONTROL SPACER: Patients received a standard spacer for administering asthma medication | No for improving adherence to medication at 3 months in asthma patients | No for exacerbations of asthma. No for reducing the frequency of wheeze or cough at 3 months |
| Chamorro 2011 | Hypertension, dyslipidemia, cardiovascular disease, type 2 diabetes and coronary heart disease | PHARMACOTHERAPY FOLLOW‐UP: The intervention consisted in follow‐up of the patients by the pharmacist. He gave written and oral information about cardiovascular prevention and adherence to the patients in the first interview. The pharmacist adopted a pharmacotherapy follow‐up program, for 4 visits over 16 to 18 weeks. The final assessment was at 32 weeks | EDUCATION: This procedure consisted of health education, written and oral material all given in 1 session at enrollment | No for adherence at 8 months | No for all clinical health outcomes |
| Chan 2007 | Persistent asthma | INTERNET‐BASED HOME MONITORING AND EDUCATION: Both groups had 6 visits scheduled at 0, 2, 6, 12, 26, and 52 weeks, with the study pediatrician and 1 of the 4 assigned nurse case managers or the pediatric clinical pharmacist case manager. The intervention group received 3 in‐person visits, at 0, 26, and 52 weeks, and the rest as virtual visits. Virtual visits included asthma education, a video recording of peak flow meter and inhaler use forwarded to the website, daily asthma diaries, and communication with the case manager electronically via the website. Patients were provided a home computer system, camera, and Internet access. On‐site in‐home instruction was provided by technical experts on equipment use and website capabilities and use. Each patient received the same models of computer and computer equipment, as well as broadband Internet access. Patients and their parents were taught how to use the equipment and how to record and to submit videos by using a computer‐mounted digital video camera, to capture the patient's peak flow meter and inhaler technique. A detailed asthma symptom diary and quality of life survey were included on the website. Patients and families were instructed regarding the submission of daily symptom diary entries. Videos were recorded and loaded on the site for the case manager, who scored them with standardized checklists and provided instruction through e‐mail back to the patient/family. Videos were sent 2 times per week for 6 weeks and then once‐weekly thereafter. Moreover, patients received the following same service as the control group: they were contacted (by e‐mail) by the case manager 2 times per week for 6 weeks and once per week thereafter, to review the asthma action and home management plans, to assess the symptom diary, to remind the patient to perform and to record peak flow measurements daily in the diary, to remind the patient to complete symptom diary information every day, to answer questions, and to intervene if needed. All patients were able to contact the case manager 24 hours per day, 7 days per week | OFFICE‐BASED VISITS: Patients were treated with an ambulatory asthma clinical pathway, with 6 visits scheduled 0, 2, 6, 12, 26, and 52 weeks after enrollment. At each visit, patients and their parents received in‐depth asthma education from the case manager, with specific subjects being determined by an asthma educational pathway. Office‐based group patients received all of their information in person at the pediatric clinic. Patients were able to contact their case manager by telephone | No for improving asthma controller medication adherence with internet‐based patient education and home monitoring for children with asthma | No for rescue medication use or emergency visits, symptoms, asthma knowledge and inhaler technique |
| Chaplin 1998 | Schizophrenia | Individual semi‐structured educational sessions discussing the benefits and adverse effects of antipsychotic drugs, including tardive dyskinesia (n = 28) | Usual care (n = 28) | No | No |
| Charles 2007 | Asthma | AUDIOVISUAL REMINDER: The intervention was an audiovisual reminder attached to the inhaler. When the alarm was switched on, it generated a single beep, which sounded once every 30 seconds for 60 minutes after the predesignated time, which was programmed into the device. The alarm stopped if the MDI was actuated or after 60 minutes if not taken. The device was programmed to emit the alarm at predetermined times twice a day. The AVRF also had a colored light, which was green before MDI use, changing to red once the MDI was taken. This function served to remind patients whether they had taken the MDI as scheduled. Follow‐up period was 12 weeks | SMART INHALER: Control participants received the same Smartinhaler as intervention participants, but it did not have the audiovisual reminder device | Yes for improving adherence to inhalers in adults and adolescents with asthma with an audiovisual reminder | No for improving clinical outcomes with an audiovisual timer device for inhalers in asthmatic adults and adolescents |
| Choudhry 2011 | Myocardial infarction or coronary artery disease | FULL PRESCRIPTION COVERAGE: The intervention involved changing the pharmacy benefits of the intervention group patients so that they had no cost sharing for any brand or generic statin, beta‐blocker, ACE inhibitor or ARB for every prescription after randomization | USUAL PRESCRIPTION COVERAGE: Control patients received usual prescription‐drug coverage | Yes for improving adherence to prevention medications after MI by providing full coverage pharmacy plans | Yes for reduction in health expenditure and improving rates of first major vascular events |
| Chung 2011 | HIV | COUNSELING: In the adherence counseling intervention, trained counselors administered 2 counseling sessions to participants prior to HAART initiation and a third session 1 month after HAART initiation. Counseling sessions around HAART initiation were based on a model of successful antiretroviral adherence promotion at a large University of Washington‐affiliated HIV treatment program in Seattle, Washington. All counseling sessions followed a written standardized protocol and lasted between 30 and 45 minutes. In the first session, counselors explored personal barriers to good adherence and taught participants about HIV, the virus that causes AIDS, antiretroviral medications, and the risks of treatment failure due to poor adherence. The second session occurred on a separate day and involved a review of a participant's understanding and readiness to begin antiretroviral medications. The third session allowed the counselor to examine practical and personal issues that the participant may have encountered on HAART. The adherence counseling intervention had been previously used and adapted at the same site in Kenya for over 2 years and was delivered in English and Kiswahili | USUAL CARE: "At HAART initiation, the study pharmacist explained the side effects of medications and problems associated with poor adherence in a 15‐min session prior to dispensing drugs. All participants, including those in the control arm, received this educational message. Participants randomized to the control group did not receive adherence counseling or an alarm device." (pg 2‐3) | Yes for improving adherence to medication at 1 month in the counseling group; No for improving adherence to medication at 18 months in counseling group; No for improving adherence to HAART in alarm group at any time point | Yes for reducing viral failure in counseling group. No for improving mortality and CD4 cell count in counseling group. No for reducing viral failure, CD4 cell count and mortality in alarm group |
| Colcher 1972 | Strep throat | Special counseling and written instructions on need to take all pills (n = 100) | Usual care (n = 100) | Yes | Yes |
| Collier 2005 | HIV | Serial, scripted, and supportive telephone calls from a nurse plus usual adherence support (same as control group; n = 142) | Usual support measures including in‐person counseling by a nurse at start of therapy and discretionary phone calls (n = 140) | No | No |
| Cooper 2010 | HIV | ONCE NIGHTLY REGIMEN: Patients in the once nightly regimen group received 1 x didanosine (DDI) enteric‐coated (EC) capsule 400 mg (250 mg if weight less than 60 kg), 2 x lamivudine (3TC) 150 mg tablet, 1 x efavirenz (Sustiva) 600 mg tablet each evening | TWICE DAILY REGIMEN: Patients in the control group received Combivir (zidovudine 300 mg + 3TC 150 mg): 1 tablet twice daily, 1 x efavirenz 600 mg tablet taken nightly | Yes for improving adherence with HAART with once nightly dosing versus twice daily dosing | Yes for viral load undetectable; No for HAART beliefs and intrusiveness |
| Costa 2008 | Acute myocardial infarction | TRANSDISCIPLINARY APPROACH: The transdisciplinary intervention consisted of clinical follow‐up, smoking cessation assistance, dietary advice and life style modification advice. The intervention was delivered by a team consisting of an endocrinologist, a cardiologist, a nurse and a dietician. There were 2 follow‐up assessment ‐ at 60 to 90 days after MI and 120 to 180 days after MI. In diabetic patients, capillary glycemia was measured (Advantage reagent strips, Roche, Indianapolis, IN, USA), lower limbs were examined, and adherence to prescribed oral antidiabetic agents and insulin was reviewed. Those patients who were still smoking were advised to stop smoking by the nurse and also by the cardiologist. No oral medication was prescribed in this regard since these drugs are not routinely provided by the Public Health System in Brazil. After the above‐described procedures, the dietitian evaluated body weight and performed a nutritional review. This review was followed by reinforcement of healthy nutritional habits, which included information on the characteristics and amount of healthy meals according to each case and also lifestyle modification reinforcement. The management plan was formulated as an individualized therapeutic alliance among the patient and family, the physician, and other members of the health care team. Finally, patients were evaluated by the cardiologist, who completed the visit with the specific medical history, physical examination and specific complementary tests. Drug prescription by the cardiologist followed the AHA guidelines for both groups (statins, antiplatelet therapy, beta‐blockers and angiotensin‐converting enzyme inhibitors). Diabetic patients were evaluated by an endocrinologist. Drug prescription by the endocrinologist followed the American Diabetes Association (ADA) guidelines for both groups | CONVENTIONAL CARE: Conventional care group received regular care. Before discharge, they were visited by a dietitian who prescribed a post‐discharge diet plan after nutritional evaluation. Then they were referred to the conventional outpatient clinic for heart care, where the patients were seen only by the appointed cardiologist. Cardiologists kept a routine schedule with the patients and were seen for no more than 15 minutes. Then these participants were asked to be present at the clinic 180 days after AMI to perform a clinical examination and to obtain blood samples | No for improving adherence to medication in patients after myocardial infarction | No for improvement in clinical improvement index; No for reduction in rate of hospitalization and deaths; Yes for increasing compliance with diet; Yes for improving compliance with visits |
| Cote 1997 | Asthma | Extensive asthma education program plus written self managed action plan based on peak expiratory flow (PEF) (n = 50) or based on asthma symptom monitoring (n = 45) | Basic information provided plus verbal action plan could be given by physician (n = 54) | No for each intervention | No for each intervention |
| Cote 2001 | Asthma | Patients in Group Limited Education (LE) (n = 30) were given a self action plan that was explained by the on call physician. The action plan used "traffic lights" (green, yellow, red) to describe specific states of asthma control based on peak expiratory flow and symptoms and actions that the patient should take for each state. Subjects were all instructed by a respiratory therapist or study nurse in the proper use of an inhaler. In addition to what patients in Group LE received, the patients in Group Structured Education (SE n = 33) participated in a structured asthma educational program based on the PRECEDE model of health education within 2 weeks after their randomization | The patients in Group C (control, n = 35) received the usual treatment given for an acute asthma exacerbation | No | No |
| Coull 2004 | Ischemic heart disease | Intervention consisted of participation in a mentor‐led group (n = 165), through attending monthly 2‐hour long meetings in community facilities over a 1‐year period. There was an average of 10 patients per group, each led by 2 mentors. The core activities covered in the program were lifestyle risk factors of smoking, diet and exercise; blood pressure and cholesterol; understanding of and ability to cope with IHD; and drug concordance. Each mentored group was also encouraged to develop its own agenda. Input was provided from a pharmacist, cardiac rehabilitation specialist nurse, dietician, welfare benefits advisor and Recreation Services. Volunteer lay health mentors, aged 54 to 74 recruited from the local community led the groups | Both intervention and control groups (n = 154) continued to receive standard care | Yes | No |
| Dejesus 2009 | HIV/AIDS | SINGLE TABLET REGIMEN (EFV/FTC/TDF): Intervention group patients were prescribed a single‐tablet regimen consisting of efavirenz/ emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) | ART: Control group patients were prescribed regular multi‐drug ART | No for change in adherence to medication in EFV/FTC/TDF arm and SBR arm at 48 weeks | No for improving QOL; Yes for improving preference of medication and ease of the regimen; Yes for HIV symptom index |
| DiIorio 2008 | HIV | MOTIVATIONAL INTERVIEWING: Intervention group receives usual adherence education and motivational interview. Participants received 5 individual MI counseling sessions with a study nurse counselor over a 3‐month period. The goal of these sessions was to help participants gain an understanding of their medication‐taking behaviors and the actions necessary to successfully maintain a high level of adherence. The counselor used a MI script to guide the interaction with the participants. During the session participants were encouraged to identify and discuss barriers to adherence, to express and resolve ambivalence about taking medications, and to support motivation to attain or maintain adherence. After each medication was discussed and an action plan developed, the counselor ended each session by summarizing the discussion and the action plan agreed upon by the participant and counselor. Session 1 was completed in‐person for all participants. Telephone sessions (for sessions 2 though 5) were conducted as needed for participants who were unable to meet the counselor in the clinic. Participants were paid USD 10 for completing the first MI session and USD 5 for each of the remaining 4 sessions. Participants in the intervention group also received a copy of the Get Busy Living video, a journal and a calendar | CONTROL: Participants randomized to the control group received the usual adherence education provided at the clinic. 3 nurse educators employed at the HIV clinic provided comprehensive adherence education to patients who are initiating or changing ART. They use a variety of teaching methods that were tailored for each individual based on factors such as education level, culture, type of regimen and time schedule. Patients were referred to the Get Busy Living staff when the nurse educators cleared them to begin taking their medications. Participants could continue to meet with the nurse educators for adherence assistance as needed after the initial education sessions | Yes for the per cent of prescribed doses taken on schedule; No for the per cent of doses taken | No for viral load and CD4 count |
| Druss 2010 | Serious mental illness | HEALTH AND RECOVERY PROGRAM (HARP): Participants in the intervention group attended up to 6 group sessions led by mental health peer specialists. Sessions covered the following topics related to chronic disease self management: 1. Overview of self management 2. Exercise and physical activity 3. Pain and fatigue management 4. Healthy eating on a limited budget 5. Medication management and 6. Finding and working with a regular doctor. During the sessions, peer educators modeled appropriate behaviors and responses, and participation from each group member helped model behavior and improve motivation for other members. Attendees are taught to develop short‐term "action plans" for choosing domains of health behavior change. This process involves identifying a problem that is of particular concern, listing ideas for solving the problem, and then developing a plan outlining specific, short‐term goals for improvement. 2 certified mental health peer specialists participated in a community‐based, 5‐day CDSMP master training course to become master trainers in the CDSMP program. Subsequently, they received 3 additional days of training from the team's principal investigator and health educator in the Health and Recovery Peer (HARP) program | USUAL CARE: Subjects assigned to usual care continued to receive all medical, mental health, and peer‐based services that they were otherwise receiving prior to entry into the study | No for improving adherence to medication in patients with severe mental illness at 6 months | Yes for improving patient activation and primary care medical services use at 6 months. No for improving physical activity, physical health‐related quality of life, and mental health‐related quality of life at 6 months |
| Duncan 2012 | HIV | MINDFULNESS‐BASED STRESS REDUCTION: MBSR aims to teach participants to respond to stressful situations ''mindfully'' ‐ a state in which one focuses on the present moment, accepting and acknowledging it without getting caught up in thoughts that are about the situation or emotional reactions. This enables people to respond to the situation by making conscious choices to respond instead of reacting automatically. The MBSR program consists of the following elements: (1) individual pre‐program intake interviews performed by the course instructor with each participant, lasting 30 minutes; (2) 8 weekly classes of 2.5 to 3 hours; (3) an all‐day silent retreat during the 6th week of the program; and (4) daily home assignments including a minimum of 45 minutes per day of formal mindfulness practice and 5 to 15 minutes of informal practice, 6 days per week for the entire duration of the course. The total in‐class contact is approximately 30 hours, and the total home assignments are a minimum of 42 to 48 hours. In addition, one to 2 additional individual interview sessions may be provided, at instructor discretion, to individual participants during the course. In addition to teaching mindfulness practices, the course includes didactic presentations that include information on stress physiology and stress reactivity. The course also addresses the effects of perception, appraisal, and attitude on health habits and behavior and on interpersonal communication | STANDARD CARE: Control group received standard care and went through the same assessment procedure as the intervention group | No for improving medication adherence in HIV patients with Mindfulness Based Stress reduction Therapy at 3 or 6 months | Yes for reducing frequency of symptoms attributable to ARTs at 3 and 6 months and distress associated with those symptoms at 3 months. No for reduction in perceived stress, depression, and positive and negative affect, at 3 and 6 months |
| Dusing 2009 | Hypertension | MULTIFACTORIAL INTERVENTION: The set of supportive measures provided for selected centers and all patients recruited in these centers is listed below. It was up to the patients to select the tools they would like to use on an individual basis. For the patient: (a) 24‐hour timer: the timer can be set to an individual time and provides an acoustic signal every 24 hours at this point of time. (b) Set of 10 reminding stickers to be positioned at prominent places at home (e.g. refrigerator and bathroom mirror). (c) Information brochure for patients with hypertension published by the German Hypertension Society. (d) Information letter for the patient. (e) Information letter the patient can give to next of kin to receive support or his therapy (e.g. spouse reminding of drug intake). (f) Home BP measurement device. (g) Booklet to document home BP measurements | STANDARD CARE: At the baseline visit, all eligible patients were started on study treatment with valsartan 160 mg daily for 4 weeks. Patients with controlled BP were continued on treatment with valsartan 160 mg. Patients not achieving BP values less than 140/90 mmHg by week 4 were then up‐titrated to valsartan 160 mg and HCTZ 12.5 mg as a fixed‐dose combination. Follow‐up visits were scheduled after 2 (third visit), 4 (4th visit), 8 (fifth visit), 14 (6th visit), 24 weeks (7th visit), and at the end of the observation period at 34 weeks (8h visit). Dispensing of the study drugs was as follows. At baseline, patients received MEMS bottles containing 48 tablets of 160 mg valsartan. At 4th and 5th visits, that is, after 4 and 8 weeks, patients received further MEMS bottles containing 48 tablets of either 160 mg valsartan or 160 mg valsartan and 12.5 mg of HCTZ depending on their BP. At 6th and 7th visits, that is, after 14 and 24 weeks of treatment, patients received MEMS bottles containing 76 tablets. Patients were instructed to take their medication per mouth with water in the morning between 0700 and 1100 hours, regardless of meals. No supportive measures were given to patients | No for improving adherence outcome in patients with essential hypertension with the use of supportive measures | No for reduction in BP |
| El Miedany 2011 | Rheumatoid arthritis | VISUAL FEEDBACK: The active group consisted of a visual feedback facility (visualization of computer charts showing the disease progression) that was added to their management protocol. Visual feedback is a relatively new tool that enables the patient to visualize as well as monitor a real‐time change of their disease activity parameters as well as the patient's reported outcome measures. Integrating electronic data recording in the standard rheumatology clinical practice facilitated the introduction of visual feedback into the standard rheumatology practice. During their visit, the patients were given the chance to view the progression of their disease on the computer, discuss the changes in their disease activity parameters, comorbidity risks, functional disability, and quality of life. The patients were assessed at 3‐month intervals for another 6 months (unless they sustained a flare up of their condition, at which time they would be reviewed earlier). Before every assessment in the clinic, every patient completed the multidimensional patient reported outcome measures questionnaire | ROUTINE MANAGEMENT: Control group patients continued their routine standard management and assessment every 3 months. All the patient's disease activity parameters, patient‐reported outcome measures (PROMs), medications, scores of falls, and cardiovascular risks were recorded and discussed verbally with the patient. Each patient was allowed to view his former completed forms and compare between his/her current scores in comparison to the earlier records | Yes for adherence to medication | Yes for improving pain score, patient global assessment, functional disability, quality of life, and disease activity score |
| Ellis 2005 | Adolescents with type 1 diabetes | Standard medical care plus Multisystematic Therapy (MST), an intensive, family‐centered, community‐based psychotherapy treatment with tailored treatment goals and interventions for each family to best treat the adherence problem. MST interventions targeted adherence‐related problems within the family system, peer network, and the broader community systems within which the family was embedded (n = 64) | Standard medical care at a hospital‐based endocrine clinic where adolescents were cared for consisted of quarterly medical visits with a multidisciplinary medical team composed of an endocrinologist, nurse, dietician, social worker, and psychologist (n = 63) | No | No for all clinical outcomes |
| Ellis 2012 | Type 1 or 2 diabetes | MULTISYSTEMIC THERAPY: Patients in the MST group received both standard medical care and treatment sessions by 5 masters‐level therapists trained to have sufficient knowledge regarding diabetes to enable them to conduct diabetes adherence interventions with families. Treatment included 1‐hour family treatment sessions, skills practice (e.g. spending 15 minutes in home to observe a caregiver implementing a reward or consequence as part of a behavior plan), attending school meetings to provide information to staff regarding diabetes care (e.g. 1‐2 hour staff training), and attending clinic visits with families (2 hours or more) | TELEPHONE SUPPORT: Control patients (telephone support) received an initial home visit where the program was explained to the adolescent and primary caregiver by either a master level therapists or doctoral students in clinical psychology or social work. Weekly phone calls (approximately 30 minutes each) focused on emotional support for diabetes care using client‐centered, nondirective counseling, assessing adherence to diabetes for the previous week, reviewing readings in the blood glucose meter, and helping the adolescent identify solutions to any barriers in their diabetes care. Non‐diabetes‐related problems such as peer, school, or family relationship problems were also addressed during the call if desired by the adolescent. Telephone support therapists completed the same formal diabetes education training completed by MST therapists | Yes for parent‐reported adherence at 7 and 12 months; No for youth‐reported adherence at 7 and 12 months | Yes for reduction in HB1Ac |
| Evans 2010 | Coronary artery disease risk/cardiovascular risk | PHARMACIST FOLLOW‐UP: The pharmacist established goals for the patient. Goals were documented in the patient records. When any of the risk factors were uncontrolled, the pharmacist alerted the patient by telephone and mail, and the physician was notified through the patient's medical record and face to face (when possible). Patients received continuous follow‐up by the pharmacist at a minimum of every 8 weeks by telephone, mail, electronic mail, or face to face appointments. Mailed letters were reserved for patients who were successfully controlled or had been recently contacted. Information delivered during follow‐up was patient‐specific and did not require that a standard content be covered. Reasons for follow‐up included 1) To communicate relevant laboratory results, including proximity to individual targets; 2)To monitor clinical status within 7 to 10 days after the initiation or change of a drug; 3) To monitor clinical status within 7 to 10 days after experiencing an adverse event 4) To ensure that the patient was able to procure necessary follow‐up appointments 5) To provide patients with clinical goal reminders, disease‐specific information, or timely topics using periodic mailers. Emphasis was placed on conducting short follow‐up contacts that reminded and reinforced the importance of drug adherence and clinical targets. All patients were followed for a minimum of 6 months | SINGLE‐CONTACT GROUP: Patients met at the beginning of the study with the study pharmacist, and received a booklet about cardiovascular disease. After that meeting they received usual care and had no more contact with the study pharmacist | No for improving adherence to statin therapy | No for improving Framingham risk score (FRS), blood pressure, lipid profile (total cholesterol, HDL and triglycerides) and hemoglobin A1C value |
| Falces 2008 | Heart failure | EDUCATIONAL INTERVENTION: A research team pharmacist carried out the intervention. It consisted of an interview at hospital release followed by telephone reinforcement. The intervention focused on information about the disorder, diet education, and information about the medication. Simple language adapted to the cultural needs of the patient was used. This was backed up by audiovisual and written material. Phone calls took place during the first 6 months and for 2 months following. Patient questions or issues we also discussed. Patients were also given a contact phone number which they could call if they had doubts about their treatment or illness | CONTROL GROUP: Visits were done at 6 and 12 months. A cardiologist provided treatment as usual and a pharmacist did a pill count | Yes for adherence to medication at 6 months; No for adherence to medication at 12 months | Yes for hospital readmission, number of readmissions and days in hospital at 6 months. Yes for number of hospital readmissons at 12 months. No for QoL and mortality at 6 and 12 months |
| Farber 2004 | Asthma | Subjects in the intervention group (n = 28) received basic asthma education; instructions on use of a metered‐dose inhaler with holding chamber; a written asthma self management plan illustrated by zones colored green, yellow, and red; a sample age‐appropriate holding chamber; and prescriptions for medication needed to implement the plan. This medication included an inhaled corticosteroid drug for everyday use and a quick‐acting bronchodilator for use as needed. The importance of seeking urgent medical care in the red zone was emphasized. 3 brief follow‐up phone calls were placed to patients in the intervention group at 1 to 2 weeks, 4 to 6 weeks and 3 months after enrollment | The control group (n = 28) received routine care | Yes (based on dispensing) | No |
| Farooq 2011 | Schizophrenia | STOPS: Participants in the STOPS arm received usual care plus specific education given to a key care supervisor about the illness and the importance of adherence; medications were provided 1 month at a time free of charge | TAU: Psychiatrists provided treatment as they would normally deliver in routine out‐patient settings. These included prescribing evidence‐based pharmacological treatments, out‐patient attendance in the psychiatry department as deemed appropriate by the consultant and brief counseling about the treatment and outcome. Participants who could not afford to buy medication had the option to seek free drug treatment from the social welfare department of the hospital | Yes for improving adherence to antipsychotic drugs at the end of 1 year | Yes for PANSS total scores, positive symptoms, and GAF scores |
| Fisher 2011 | HIV | LIFEWINDOWS: The intervention was computer‐based, interactive ARV adherence promotion called LifeWindows developed based on the Information‐Motivation‐Behavioral skills (IMB) model. The nature of this intervention is to identify and address, through interventions, an individual's deficits in adherence‐related information, motivation, and behavioral skills. The intervention activities consisted of 20 different interactive activities that would be selected by the participants according to their goals. Patients on average spent 26 minutes to complete the full intervention with an average of 8 min dedicated to adherence intervention modules. Participants received USD 20 for completion of each session. Participants completed 1 session per month over 18 months | STANDARD OF CARE: Control patients received standard of care at the clinic they attended. Average total time spent to complete the full control session was 14 min. Participants received USD 20 for completion of the session per month over 18 months | Yes for increasing adherence to ARV in on protocol patients at the end of 18 months; No for increasing adherence to ARV in intent to treat at the end of 18 months | No for improving viral load at 18 months of intervention |
| Fortney 2007 | Depression | TELEMEDICINE‐ENHANCED ANTIDEPRESSANT MANAGEMENT (TEAM): Patients at intervention sites received a stepped‐care model of depression treatment for up to 12 months. Treatment intensity was increased for patients failing to respond to lower levels of care by involving a greater number of intervention personnel with increasing mental health expertise. The intervention involved 5 types of providers: (1) PCPs located at CBOCs; 2) consult telepsychiatrists located at parent VAMCs; (3) an off‐site depression nurse care manager (RN); (4) an off‐site clinical pharmacist (PharmD); and 5) an off‐site supervising psychiatrist. The consult‐telepsychiatrist accepted consultations or referrals from PCPs. The supervising psychiatrist provided clinical supervision to the care manager and clinical pharmacist via weekly face‐to‐face meetings. Patients and providers could choose either watchful waiting or antidepressant treatment (Step 1). Nurse care manager encounters were conducted via telephone and were scripted to enhance standardization and reproducibility. During the initial care management encounter, patients were: (1) administered the PHQ9 symptom monitoring tool; (2) educated and activated using a semi‐structured script4; and 3) assessed for treatment barriers using semi‐structured scripts for endorsed barriers. Follow‐up encounters to monitor symptoms, medication adherence, and side effects were scheduled every 2 weeks during acute treatment and every 4 weeks during watchful waiting or continuation treatment. Non‐adherent patients or those experiencing severe side effects were administered semi‐structured scripts.3 A trial was considered to have failed in the acute phase if the patient: (1) was non‐adherent to the medication, (2) experienced severe side effects, (3) experienced 5‐point increase in their PHQ9 score, or (4) did not respond (50% decrease in PHQ9 score) after 8 weeks of antidepressant therapy. All feedback was provided to PCPs using the electronic medical record. Progress notes reporting failed trials requested an electronic co‐signature from the PCP. If the patient did not respond to the initial antidepressant, the pharmacist conducted a medication history and provided pharmacotherapy recommendations to PCPs via an electronic progress note (Step 2). The pharmacist also provided non‐scripted medication management over the phone to patients experiencing severe side effects or problems with non‐adherence. If the patient did not respond to 2 antidepressants trials, the protocol was to recommend a telepsychiatry consultation followed by additional treatment recommendations to the PCP (Step 3) | USUAL CARE: Control groups received usual care. Usual care patients like the intervention group were provided with provider education and patient education. Also, the screening results were entered into the electronic medical record | Yes for improving adherence to antidepressant medication in depressed patients at 6 and 12 months | Yes for increased response and no for remittance in the intervention group at 6 months. Yes for improving odds of remittance and no for response in intervention group at 12 months. Yes for improving satisfaction in intervention group at 12 months. No for improving physical health score at 6 and 12 months. Yes for improving mental health score at 12 months and not at 6 months |
| Friedman 1996 | Hypertension | Telephone‐linked computer system (TLC) ‐ an interactive computer‐based telecommunications system that converses with patients in their homes between office visits to their physicians (n = 156) | Regular medical care (n = 145) | Yes | Yes |
| Gallefoss 1999 | Asthma or chronic obstructive pulmonary disease (COPD) | An educational intervention consisting of a specially constructed patient brochure, 2 2‐hour group sessions (separate groups for asthmatics and patients with COPD) concentrating on pathophysiology, anti‐obstructive medication, symptom awareness, treatment plans, and physiotherapy. One or 2 40‐minute individual sessions were supplied by both a nurse and a physiotherapist. At the final teaching the patients received an individual treatment plan on the basis of the acquired personal information and 2 weeks of peak flow monitoring (n = 39 asthmatics, n = 32 COPD patients) | Usual care from GP (n = 39 asthmatics, n = 32 COPD patients) | No | No |
| Gamble 2011 | Asthma | INTERVENTION: The intervention was individualized, provided psycho‐education and was led by an experienced registered nurse with basic level psychotherapy training for 12 months to improve adherence to medication. In addition to standard asthma care, intervention group subjects were offered up to 8 months of individual visits within a 12‐week period. Although the proposed intervention was unique in its design, to increase the internal validity of the study, the Compliance Therapy Model was used to provide the underpinning theoretical framework. This model encompassed the Transtheoretical Model of Change, Motivational Interviewing and Cognitive Behavioral Therapy principles, providing a flexible short‐term intervention using patient's individual reasons for non‐adherence as a guide to plan intervention content. The model used a non‐confrontational technique which elicited self motivation and provided a process to resolve ambivalence towards medication taking | STANDARD ASTHMA CARE: All participants received standard asthma care at the difficult asthma service but the control group did not receive any further intervention. Subsequent follow‐up visits for the control group was conducted at 6 months and 12 months post‐recruitment | Yes for percentage of prescriptions filled. Yes for number of participants in intervention group filling prescriptions | Yes for reducing the daily prescribed dose of maintenance prednisolone. No for improving hospital admissions, FEV % predicted, quality of life, asthma control score, anxiety, and depression |
| Gani 2001 | Seasonal rhinitis and asthma | B group (n = 35) with drug therapy plus training on the use of nasal spray, and C group (n = 36) the same as B plus a lesson on rhinitis and asthma | A group (n = 30) with drug therapy alone | Yes for A versus B + C | Yes: between group A and group C in respiratory symptoms. Yes, in the use of inhaled albuterol (Fisher test) among the groups was observed (A versus B plus C: P value = 0.005; A versus C: P value = 0.005) |
| Gensichen 2009 | Major depression | CASE MANAGEMENT: The intervention was in accordance with Chronic Care Model, which emphasizes proactive support for the patient by the entire practice team. 1 healthcare assistant from each practice assigned to the intervention group in 2 workshops (an 11‐hour and a 6‐hour workshop). This interactive training included information on depression, communication skills, telephone monitoring, and behavioral activation for the patient. The healthcare assistants contacted their patients by telephone twice a week in the first month and then once a month for the following 11 months. They monitored depression symptoms and adherence to medication by using the Depression Monitoring Context List. Healthcare assistants also encouraged patients to follow self management activities, such as medication adherence and activation for pleasant or social activities. The assistants provided this information to the family physician in a structured report that stratified the urgency of the contact by a robot scheme. Family physicians in both the intervention and control groups received training on evidence‐based depression treatment guidelines | USUAL CARE: Patients in the control group were given usual care | Yes for improving adherence to medication at 12 months | Yes for reducing depression symptoms score and increased response and remission in intervention group at 12 months. No for quality of life scores and number of family physician or mental health specialist contacts at 12 months |
| Ginde 2003 | Macrolide antibiotic treatment | Patients in the ED group (n = 38) were provided a full course of azithromycin (6 x 250 mg) at no charge and given instructions on the proper dose and frequency before discharge from the ED | Patients in the pharmacy group (n = 36) received a written prescription for a full course of azithromycin before discharge from the ED | No | No. The prescription filling rate for the control group is based on the assumption that control patients used a participating pharmacy 8 blocks away that provided the drugs free of charge ‐ patients were apparently not asked if they filled their prescription elsewhere. The "course completed" rate is based on self report on a telephone call ‐ no indication that interviewers were blinded to group; nor was the exact question given (if there was one). Technically, this study qualified for the review, but the reliability and credibility of the measures are suspect. At least the question of the control group's filling of prescriptions could have been cleared up. The intervention is also impractical in any setting where giving drugs out for free is not possible |
| Girvin 1999 | Hypertension | Enalapril 20 mg once daily (n = 27). Cross‐over study, with 4‐week study periods | Enalapril 10 mg twice daily (n = 27). Cross‐over study | Yes | No |
| Gould 2009 | Acute cardiac event | DISCHARGE NURSING INTERVENTION (DNI): The discharge nursing intervention consisted of written discharge materials and telephone follow‐up by an expert cardiovascular nurse. Expert nurses were defined as those having advanced education and clinical expertise in the care and management of this population. Delivery of the intervention was time‐sensitive. The intervention was offered at discharge and continued within 24 hours of discharge. DNI group received a packet containing group instructions, medication review materials, a medication pocket card, suggested Internet sites, copies of the interview tools, and the Revised Illness Perception Questionnaire (IPQ‐R) instrument | USUAL CARE: Control group patients received routine discharge materials and usual care. Subjects in the control group received an envelope containing group instructions, copies of interview tools, and the IPQ‐R | No for improving adherence to medication in early discharge interventional cardiology patients | No for use of urgent care |
| Gray 2012 | Ocular hypertension (OHT), open‐angle glaucoma (OAG) | INDIVIDUALIZED PATIENT CARE: Patients in the individualized care group received standard care plus an individualized care plan implemented by a glaucoma trained nurse. This included a 45‐minute assessment of health care needs and beliefs with supplied booklets and drop diaries, a 20‐minute educational session, and a 10‐minute training session on instilling eye drops. A 1‐year follow‐up care plan was designed and implemented according to healthcare needs, based on education and support, which was tailored to gaps in glaucoma knowledge, pre‐existing beliefs, and ability to manage an eye drop regimen. Patients were given the nurse's contact telephone for advice or assistance between consultation. Follow‐up involved ongoing training and support by both face‐to‐face and telephone consultations. This incorporated a review of drop diaries in the initial weeks of therapy (these were continued if found beneficial as a reminder tool), reminders to collect and use drops, and repetition of information as required. Needs were reassessed and the level of support adjusted accordingly at the end of each consultation. The intervention nurse was the same throughout, and the intervention was guided by prescriptive documentation | STANDARD CARE: Standard of care is not definitively described. Education, advice, and support varies from clinic to clinic within Manchester Royal Eye Hospital but is limited for many patients. No further contact after initial consultation | Yes for improving refill adherence at 12 months. Yes for improving self reported adherence at 12 month follow‐up | No for mean IOP, IOP fluctuation, and clinical management at 12 months and mean IOP at 24 months; Yes for IOP fluctuations and clinical management at 24 months |
| Hamann 2007 | Schizophrenia or schizophreniform disorder | SHARED DECISION‐MAKING (SDM): The intervention was designed to inform patients about their treatment options and to prepare them for a planning talk with their physicians. A printed 16‐page booklet covering the pros and cons of oral versus depot formulation, first‐ versus second‐generation antipsychotics, psychoeducation, and type of socio‐therapeutic intervention was presented to the patients through the head nurse of the ward as soon as the psychiatrist in charge considered them able to cooperate. Trained nurses assisted the patient to work through the booklet. Within the decision aid, patients were asked to write down their experiences with previous antipsychotic medication and to indicate their preferences regarding the different options on each topic. Nurses were advised to answer any questions of the patients and to encourage them to state any point of view contrary to that of the doctor. They were also instructed to postpone the participation of patients in the study if serious thought disturbances or delusional misinterpretations were detected while working through the booklet. The average time for working through the booklet was 30 to 60 minutes. Patients met their physicians within 24 hours after having worked through the decision aid with their nurse. The aim of these meetings, "planning talks", was to reach an agreement between patient and psychiatrist on the further treatment according to the preferences indicated by the patient in the booklet. Like nurses, physicians were also trained about the SDM and required communication skills | USUAL CARE: "Patients in the control group were treated "as usual", thus they did not receive the decision aid and there was no arrangement for an extra planning talk" | No for improving adherence to antipsychotic medication at 6 and 18 months | No for reducing rehospitalizations within 6 and 18 months after discharge. No for improving CGI and GAF scores at 18 months |
| Haynes 1976 | Hypertension | Tailoring, self monitoring of pills and blood pressure, rewards for higher adherence and lower blood pressure (n = 20) | Usual care (n = 18) | Yes | No |
| Hederos 2005 | Children with asthma | Group meetings (weekly x 3, then 6 months later, 1.5 hours each) for parents of children with asthma held by a multidisciplinary team (pediatrician, nurse, psychologist) + usual care and basic education (see Control group strategy; n = 32) | Family received education about asthma at the first visit to the clinic. They received a written treatment plan that tailored the lowest effective dose. Treatment was stopped if the child had no asthma for 6 months (n = 28) | Yes for parents and doctors estimated adherence on a visual analogue scale (VAS), for poor adherence and for greater than or equal to 100% adherence. No for estimated adherence tracked from diaries, for good adherence, and for verified adherence from measured doses | No for all clinical outcomes |
| Heisler 2010 | Diabetes | RECIPROCAL PEER SUPPORT: After the baseline assessment, patients in the RPS group attended a 3‐hour group session facilitated by a care manager and a research associate. In the first half of the session, patients' laboratory and blood pressure results were reviewed and action planning was introduced. In the 2nd half, patients received brief training in basic peer communication skills and were paired with another age matched patient in their cohort. Peer partners were encouraged to call each other at least once a week using an interactive, voice‐response–facilitated telephone platform that recorded call initiation, frequency, and duration; enabled partners to contact each other without exchanging telephone numbers and to set periods during which calls could be blocked; and generated automated reminders every 7 days if no peer calls were attempted. During a reminder call, patients could be transferred automatically to their peer partner's number. The system also allowed patients to leave voice messages for research staff or care managers. At the end of the initial session, patients were given a DVD that demonstrated peer communication skills and a diabetes self management workbook that they could use to help guide their peer telephone calls. Patients were also offered 3 optional 1.5‐hour group sessions at months 1, 3, and 6. These were completely patient‐driven sessions at which patients were encouraged to share concerns, questions, strategies, and progress on their action plans. Sessions were facilitated by a care manager and a research associate. Research associates were present to help maintain intervention fidelity by encouraging nondirective facilitation of group discussions and to complete a checklist of key areas covered and communication skills used in each session | NURSE CARE MANAGEMENT: At baseline and 6‐month follow‐up, all study patients had their HbA1c level and blood pressure checked and were informed of the results and the most recent cholesterol values were in their medical record. Patients in the NCM group then attended a 1.5‐hour session, led by a care manager, to review their laboratory and blood pressure results, ask questions, and receive information on VA care management services. They were provided their assigned care manager's contact information and encouraged to schedule follow‐up telephone calls or face‐to‐face visits with that care manager. Each patient was also provided with diabetes self management educational materials. Patients in the NCM group thus received enhanced usual care, because even though they would all be eligible for nurse care manager support at the study sites, many patients are not aware of and do not avail themselves of this service unless referred by their physician | No for improving adherence to medication at 6 months | Yes for reducing the mean HbA1c level and increasing social support score at 6 months. No for reducing blood pressure and diabetes‐related emotional distress at 6 months |
| Henry 1999 | H. Pylori infection | 10 days of omeprazole 20 mg twice daily, amoxicillin 500 mg 3 times a day and metronidazole 400 mg 3 times a day, verbal advice on medication use and its possible side effects in an initial 20‐minute consultation. Patients also received medication in dose‐dispensing units, an information sheet on H. Pylori treatment, and a medication chart. Compliance in intervention group patients was also encouraged by a phone call 2 days after the start of therapy (n = 60) | 10 days of omeprazole 20 mg twice daily, amoxicillin 500 mg 3 times a day and metronidazole 400 mg 3 times a day, verbal advice on medication use and its possible side effects in an initial 20‐minute consultation (n = 59) | No | No |
| Hill 2001 | Rheumatoid arthritis | The intervention group (n = 51) received 7 x 30 minute one to one sessions of patient education | The control group (n = 49) received standard management | Yes for improving adherence to D‐penicillamine (DPA) for rheumatoid arthritis | No for improving clinical outcomes of plasma viscosity, c‐reactive protein, articular index, morning stiffness and pain score |
| Holland 2007 | Heart failure | HEARTMED PHARMACIST INTERVENTION: The pharmacist arranged a home visit, within 2 weeks of hospital discharge, at a time when they could meet the patient and any carer(s). Where appropriate, pharmacists educated the patient/carer about heart failure and their drugs and gave basic exercise, dietary, and smoking cessation advice. They also encouraged completion of simple sign and symptom monitoring diary cards (including monitoring body weight), removed discontinued drugs (with the patient's consent), fed back recommendations to the general practitioner, and fed back to the local pharmacist any need for a drug adherence aid (for example, a Medidos or Dosett container). We provided all pharmacists with a detailed manual describing the expected components of their visit and asked them to deliver education in line with advice given in the British Heart Foundation's booklet Living with Heart Failure, which they left with patients after the first visit. Pharmacists completed a standardized visit form during each visit. 1 follow‐up visit occurred at 6 to 8 weeks after discharge to review progress and reinforce original advice. We also recorded a selection of pharmacists' visits to investigate the intervention's delivery and the pharmacists' communication skills | USUAL CARE: The nature of the intervention meant that no clear "placebo" could be provided. Participants were told after randomization which group they were in. Those in the control group received usual care | No for improving medication adherence | No for improving quality of life and reducing ED visits and admissions |
| Holstad 2011 | HIV | KHARMA INTERVENTION: The KHARMA intervention consisted of 8 group sessions using motivational interviewing delivered in a group format. It was designed to empower women to make decisions and develop strategies about taking ART as prescribed and consistently using risk reduction behaviors, such as condom use and to overcome resistance/ambivalence to both. The sessions lasted about 1.5 to 2 hours, and were led by trained MI nurses. The first and last session focused on both adherence and risk behavior, 3 sessions were devoted to adherence only and 3 to risk reduction behaviors only, including a session on disclosure which is important to risk reduction as well as adherence. Each session included a discussion of goals and goal setting related to the topic. MI techniques were incorporated into every session. In keeping with the autonomy support spirit of MI, participants as a group chose which topic they wanted to address first. The majority of groups (n = 14) chose medication adherence as the first topic | HEALTH PROMOTION PROGRAM: The control group sessions were equivalent in length and time to the MI group and were led by trained nurses and a health educator. This group used health education techniques of lecture/discussion/educational games and focused on nutrition, exercise, stress recognition, and women's health issues tailored to the HIV‐positive woman. Participants received a manual containing content and supplementary materials for each session. Adherence and RRB were not addressed in the HPP and facilitators were instructed to redirect the group if these issues came up | No for improved adherence to ART | Yes for CD4 counts at 9 months. No for all other outcomes |
| Hou 2010 | oral contraceptive use | TEXT MESSAGING: Participants received daily text‐message reminders. During the 3‐month study period, each participant assigned the intervention received a daily text message, "Please remember to take your birth control pill," sent at a designated time chosen by the participant. | USUAL CARE: Patients in the control group received usual care and were not offered additional medication reminders. | No for improving adherence to oral contraceptives. | No for pregnancy at 3 months. |
| Howe 2005 | Children with type 1 diabetes | 2 intervention groups, standard care (see Control) plus: 1) Education (ED) ‐ One‐time session by the study co‐ordinator that aimed to provide families with basic diabetes management skills (n = 21). 2) Education and telephone case management group (ED and TCM) ‐TCM consisted of standardized telephone calls which reviewed blood sugars, safety issues, problem‐solving skills, diet and meal planning, and changing insulin dose, as well as parenting and behavior management skills with parents as needed (n = 26) | Standard care (SC) from a nurse practitioner and endocrinologist (n = 28) | Yes for the adherence questionnaire (ADH), in comparison between the ED and TCM group versus the SC group | No for both intervention groups |
| Howland 1990 | Acute infections | Warnings about potential adverse effects of drugs (n = 50) | No warnings about adverse effects of drugs (n = 48) | No | No |
| Huguelet 2011 | Schizophrenia or other non‐affective psychoses | RELIGIOUS AND SPIRITUAL ASSESSMENT: The intervention was delivered by psychiatrists who were trained by the researchers. Psychiatrist attended a 90‐minute training session during which they were informed about the rationale for taking into account the spiritual dimension in the treatment of patients with schizophrenia and how to conduct a spiritual assessment. They were made aware of how their own religious and spiritual experiences could influence their identity and world view, as well as how their attitudes toward such experiences might introduce biases into clinical assessment and treatment. Finally, psychiatrists were reminded to show respect for patients with different religious and spiritual backgrounds. Psychiatrists used a semi‐structured interview guided by the following topics: religious and spiritual history, effects of illness on spirituality or religiousness, current spiritual or religious beliefs and practices, subjective importance of religion in general, subjective importance of religion in coping with the illness, synergy of religion with psychiatric care. After each assessment the psychiatrist met with 2 of the authors, a psychiatrist and a psychologist of religion. In these sessions the individual patient was discussed for 10 to 40 minutes, depending on the clinical context. The participating psychiatrist reported the outcome of his or her spiritual assessment and was given guidance and advice, similar to clinical coaching; when needed, a more thorough discussion from a psychotherapeutic perspective was undertaken | USUAL CARE: "For the control group, psychiatrists were instructed to avoid speaking about religious issues during the 3‐month follow‐up period unless patients spontaneously brought up the subject." (pg 81) | No for improving medication adherence | No for improving positive and negative syndrome scale, global assessment of functioning, WHO quality of life instrument, recovery assessment scale, and social functioning questionnaire. Yes for improving the willingness to ask for help at 3 months follow‐up |
| Janson 2009 | Moderate‐to‐severe persistent asthma | SELF MANAGEMENT EDUCATIONAL INTERVENTION: Participants in the individualized self management group received both the self monitoring of the control group plus an individualized self management component. Self management sessions were held by a certified asthma educator and respiratory therapist. The sessions consisted of asthma facts and medication actions and individualized components such as verbal and graphic interpretation of spirometric results, peak flow trends, metered dose inhaler technique error, and skin allergen results (with strategies to control specific personal environmental exposures). The peak flow monitor was modified for the intervention group to use a traffic light analogy and correlated to a simple written action plan | SELF‐MONITORING ALONE: Control patients attended the same number of visits as intervention patients, but control visits were only for data collection. During each phase of the trial, all participants measured morning peak flow with an electronic peak flowmeter (Airwatch; iMetrikus, Carlsbad, Calif) and also recorded their daily values in a diary. All participants were told that higher peak flow numbers meant their airways were more open and lower numbers meant their airways were more closed. An electronic medication monitor, which concealed readings from the subject (Doser CT; MediTrack, Hudson, Mass), was placed on each ICS inhaler. Participants also monitored daily symptoms, night‐time awakenings, and tabulated ICS and inhaled b‐agonist (IBA) use in the diary. Data from the electronic monitors and diary pages were collected at each study visit | Yes for maintaining > 60% adherence during the intervention period; No for mean adherence, mean change in adherence, and for maintaining > 60% adherence at the end of the study | Yes for night‐time awakenings during the study period, beta‐agonist use during the intervention period, and mean neutrophil count over the study period. No for FEV1, morning peak flow, perceived asthma control, quality of life, symptom score, ECP, symptom‐free days, night‐time awakenings during the intervention, beta‐agonist use over the entire study period, neutrophil counts during the intervention, and eosinophils and tryptase counts |
| Jarab 2012 a | Type 2 diabetes | PHARMACIST INTERVENTION: Patients in the pharmacist intervention group received structured patient education and discussion about type 2 diabetes, risks and complications from diabetes, the prescribed drug therapy, proper dosage, side effects, and the importance of medication adherence. The pharmacist also emphasized lifestyle management (changing unhealthy dietary habits that affect blood glucose, blood pressure and lipid levels; regular physical activity; and monitoring and record blood glucose levels). Smokers were referred to a hospital‐run smoking cessation program. A special booklet on diabetes and lifestyle changes was given to each patient. 8 weekly telephone calls were made by the pharmacist to discuss and review prescribed therapy, emphasize the importance of adherence, and to answer patient questions or address concerns. Each call average 20 minutes | USUAL CARE: Control patients (n = 85) received usual care by medical and nursing staff (patient assessment; 3‐ or 6‐month blood glucose and blood pressure measurements; advice on self monitoring blood glucose, and nutrition counseling) | Yes for improving medication adherence at 6 months | Yes for A1c values, systolic and diastolic blood pressure, and LDL‐C levels; No for HDL‐C levels and BMI |
| Jarab 2012 b | Chronic obstructive pulmonary disease | PHARMACIST INTERVENTION: Intervention participants received structured education about chronic obstructive pulmonary disease (COPD) and management of its symptoms from a clinical pharmacist in a separate room at the outpatient clinic. The pharmacist also completed a medication table designed specifically to discuss types, indications, doses, frequency of administration, and possible side effects for each prescribed medication. The importance of simple exercises symptoms control and the technique for expectoration were discussed with the intervention patients. A booklet on these techniques was prepared to assist in the education session and the patients were given a copy to take home with them. The clinical pharmacist used the motivational interviewing technique with the aim of improving adherence to the prescribed treatment. Patients who still smoked were referred to a special smoking cessation program within the hospital | TREATMENT AS USUAL: Controls did not receive pharmacists care | Yes for improving adherence to medication at 6 months | No for change in forced expiratory volume in 1 second (FEV1) and BMI at 6 months. No for difference in health‐related quality of life and emergency department visit for acute exacerbation of COPD at 6 months. Yes for reducing hospital admissions for acute exacerbation of COPD at 6 months |
| Jiang 2007 | Coronary heart disease (angina pectoris or myocardial infarction) | CARDIAC REHABILITATION PROGRAM: Patients in the intervention group received a 12‐week, hospital‐initiated, home‐based multifaceted cardiac rehabilitation intervention led by a nurse. Phase I of the intervention involved in‐hospital individual and family education about CHD and self management principles, medication management, angina prevention and management, physical exercise, dietary management, smoking cessation, and family support. All sessions employed principles of adult learning and were short to facilitate time for discussion. All participants received a self help practical workbook. In Phase II of the intervention provided home‐based supervision, coaching and support by a experienced cardiac nurse over 12 weeks using home visits and telephone calls that included goal setting, practice, monitoring, problem‐solving and reinforcement, with iteration of this process to ensure the achievement of mutually set behavioral goals on a daily basis and used a log record for goal‐directed self reporting, self monitoring and self reinforcement of daily rehabilitative behaviors and mobilization of the family to join the behavioral change and provide appropriate support | ROUTINE CARE: Control patients received conventional care and were not offered any additional interventions | Yes for improving adherence to medication at 3 months. No for improving adherence to medication at 6 months | Yes for reducing serum lipids (TG, TC, LDL ‐ except for HDL) and systolic and diastolic BP at 3 months. No for body weight at any point and blood pressure at 6 months |
| Johnson 1978 | Hypertension | (a) Self monitoring of blood pressure at home (n = 34); (b) Monthly home visits by a research assistant (n = 33); (c) Both a and b (n = 35) | Neither intervention (n = 34) | No for each intervention | No for each intervention |
| Johnson 2011 | HIV/AIDS | BALANCE PROJECT EXPERIMENTAL INTERVENTION: The intervention was 5 60‐minute individual counseling sessions with each session designed around topics relevant to ART side effects coping. Intervention sessions followed a standard structure and set of activities, but were individually tailored to participants' specific life contexts, stressors, and goals. Participants received USD 30 at the 3‐month assessment if they completed all 5 sessions prior to that assessment interview. The intervention was delivered between months 3 and 6 of the study | USUAL CARE: Control group participants received treatment as usual and received no active psychosocial interventions prior to the final trial assessment interview | Yes for improving adherence to ART medication at 15 months | No for change in SECope Positive Emotion Focused Coping, Taking Side Effect Medications, and Non‐Adherence subscales |
| Kalichman 2011 | HIV | INTEGRATED INTERVENTION: Intervention was an integrated risk reduction and adherence intervention based on the conflict theory of decision‐making. It consisted of a 45‐minute one to one orientation and goal setting with 1 of the group facilitators before 5 120‐minute group sessions and a 60‐minute post group one to one counseling session, conducted by facilitators/interventionists. Assessment was done at baseline, 3, 6, and 9‐month intervals for a total of 12 months of follow‐up | ATTENTION CONTROL CONDITION: Comparison intervention group received 45‐minute one‐on‐one orientation (with 1 facilitator), 120‐minute 5 group sessions (with male‐female facilitator pairs containing 8 to 10 participants of mixed gender and sexual orientation) and a 60‐minute one‐on‐one post‐group counseling session. The first group session focused on building group cohesion and discussed how to access quality health information. The remaining 4 group sessions covered detecting early warning signs of cancer, breast and testicular self examination, nutrition decision‐making, healthy food selection, planning exercise, and relaxation. The final individual counseling session set personalized health improvement goals | Yes improved adherence to ART over 12 months | Yes for sexual risk behavior and STI. Yes for adherence and prevention strategies and risk compensation beliefs. No for viral load |
| Kato 2008 | Cancer | CANCER TARGETED VIDEO GAME: The intervention participants were given a mini‐computer containing commercial game plus the intervention game, which was a video PC game called Re‐Mission47. In this game, players control a nanobot, "Roxxi", in 3‐dimensional environments within the bodies of young patients with cancers that commonly are diagnosed in AYA. Game content was engineered to address behavioral issues that were identified in literature reviews and preproduction targeting studies as critical for optimal AYA patient participation in cancer treatment. Video‐game play includes destroying cancer cells and managing common treatment‐related adverse effects such as bacterial infections, nausea, and constipation by using chemotherapy, antibiotics, antiemetics, and a stool softener as ammunition. To win, players control the nanobot, Roxxi, to ensure strategically that virtual patients engage in positive self care behaviors, such as taking oral chemotherapy to fight cancer cells, taking antibiotics to fight infection, taking stool softeners to prevent bowel perforations, practicing good mouth care to combat mucositis, using relaxation techniques to reduce stress, and eating food to gain energy. Neither the nanobot nor any of the virtual patients "die" in the game. If players "fail" at any point in the game, then the nanobot powers down and players are given the opportunity to try the mission again. Players had to complete missions successfully before moving on to the next level. Participants were instructed to play for at least 1 hour per week during the 3‐month period | COMMERCIAL VIDEO GAME: The control patients were provided a commercial video game ‐ A PC version of Indiana Jones and the Emperor's Tomb served as the control game because the play structure and controller interface closely resembled that of Re‐Mission | No for self reported adherence. Yes for improving adherence to chemotherapy as evidence by 6MMP concentration alone or combined 6MMP and 6 TG concentrations | Yes for improving cancer knowledge and self efficacy; No for improving QOL, stress and control |
| Katon 2001 | Depression | Patient education, 2 visits with a depression specialist, telephone monitoring and follow‐up (n = 194) | Usual care (n = 192) | Yes | Yes for SCL‐20 scores and depressive symptoms. No for episodes of relapse/recurrence |
| Kemp 1996 | Acute psychosis | 4 to 6 sessions of compliance therapy that focused on illness, conceptualization of the problem, symptoms, side effects of treatment, and the stigma of drug treatment (n = 25) | 4 to 6 session non‐specific counseling (n = 22) | Yes | Yes for global functioning assessment. Yes for full version of the brief psychiatric rating scale. No for the abridged version of the brief psychiatric rating scale. No for dose of antipsychotic drug |
| Kemp 1998 | Psychotic disorders | 4 to 6 sessions of compliance therapy that focused on illness, conceptualization of the problem, symptoms, side effects of treatment, and the stigma of drug treatment (n = 39) | 4 to 6 session non‐specific counseling (n = 35) | Yes, at 12 months. | No, at 12 months, for the 7‐item version of the Brief Psychiatric Rating Scale. Yes, at 12 months, for the Global Assessment of Function. Yes, at 6 months, for the Schedule for Assessment of Insight |
| Khdour 2009 | Chronic obstructive pulmonary disease | PHARMACIST INTERVENTION: The intervention was individualized and tailored for each patient by the clinical pharmacist based on disease knowledge, smoking status, medication adherence, self efficacy in managing breathing difficulty, and exercise and diet habits. Intervention patients were educated individually by the clinical pharmacist (in a structured fashion) on COPD, their prescribed medication, the importance of adherence, inhaler technique (written information was provided) and the management of COPD symptoms. The clinical pharmacist ensured that the patient knew the indications and doses of each medicine, and was able and willing to use the inhaler devices prescribed. The clinical pharmacist also discussed with the intervention patients the importance of simple exercises that patients can do at home (e.g. upper and lower limb exercises and relaxation techniques), symptom control (pursed lip technique) and the technique for expectoration (huff and puff technique). The pharmacist demonstrated these techniques and then asked the patients to carry out the techniques to ensure that they fully understood how to perform them. A booklet on these techniques was prepared to assist in the education session and the patients were given a copy to take home with them. Advice, using the motivational interviewing technique, was provided to the patients who still smoked and referral to a special smoking cessation program run within the hospital was made. A customized action plan for acute exacerbations, including advice to GPs to provide a prescription for an antibiotic (amoxicillin/clavulanic acid) and an oral corticosteroid to be initiated promptly by patients for exacerbations,was developed for each patient. The clinical pharmacist through motivational interviewing attempted to increase the intervention patients' self efficacy to manage or avoid breathing difficulty while participating in certain activities. The interventions were tailored according to the preliminary assessment, i.e. checklists of patients' needs were prepared by the research pharmacist and forwarded to the clinical pharmacist to discuss with the patients. The initial intervention lasted for approximately 1 hour for non‐smoker patients and slightly longer for patients who currently smoked. At each outpatient clinic visit (every 6 months arranged by the hospital consultant), intervention group patients received reinforcement of the education on COPD and its treatment from the clinical pharmacist. In addition, follow‐up telephone calls by the clinical pharmacist to reinforce the education and motivate the patients to achieve their goals were made at 3 and 9 months, i.e. between outpatient clinic appointments | USUAL CARE: Control patients received usual hospital outpatient care from medical and nursing staff | Yes for improving adherence to medication at 6 and 12 months | Yes for reducing the number of exacerbations of COPD and hospitalizations at 12 months. Yes for improving symptoms and impact but no for improving activity at 6 and 12 months. No for change in forced expiratory volume in 1 second and body mass index at 12 months |
| Kimmel 2012 | No specific clinical problems; patients just needed to be on warfarin | LOTTERY‐BASED INCENTIVES: Patients in the intervention group were offered financial incentives to remain adherent. All patients were provided with an Informedix Med‐eMonitor System, which has a display screen and separate medication compartments in which to place their warfarin. The monitor connects to an analog telephone line. They were enrolled in a daily lottery in a daily lottery, administered via the Med‐eMonitor, with an expected daily value of USD 3, or (2) no lottery intervention. participants had a 1 in 5 chance of a USD 10 reward and 1 in 100 chance of a USD 100 reward each day if they opened the monitor's pill compartment and confirmed that they took their warfarin as prescribed that day. If patients were told to not take warfarin on a particular day, they would only be eligible for the lottery if they did not take a pill that day | CONTROL: Patients in the control arm were set up with the Med‐eMonitor in order to measure medication adherence. Participants were also seen by their anticoagulation clinic practitioner as they normally would and by the study staff at baseline, 2 weeks, 3 months, and 6 months | No for improving overall adherence. No for improving adherence in a priori group with INR above target range | No for overall anticoagulation control. Yes for anticoagulation control in subjects below target range and no for subjects above target range |
| Klein 2009 | Rejection episodes in liver transplanted patients | PHARMACEUTICAL CARE: In addition to routine clinical care, patients in the intervention group received pharmaceutical care services provided by a dedicated hospital pharmacist. The pharmaceutical care program usually started about 1 week before discharge from the transplant surgery unit. The hospital pharmacist met with the patient 3 to 4 times and educated him on different issues regarding immunosuppressive medication, for example, action of the drugs, side effects, interactions, vital signs, laboratory data, and discharge medication. On discharge, the hospital pharmacist handed out and explained written information, including a discharge medication plan, information regarding the immunosuppressive therapy, and a diary for documenting vital signs and laboratory data. During the first year after transplantation, the patient met the pharmacist at least once per quarter year and at maximum once per month. During these meetings the pharmacist discussed with the patient changes in medication, laboratory values, and drug‐related problems. Preferably, family members were involved. In addition, the hospital pharmacist reviewed the patients' drug therapy, to minimize drug‐related problems, and simplify drug regimens | CONTROL: Patients in the control group did not receive pharmaceutical care but they received routine clinical care. from the same hospital pharmacist as the intervention group | Yes for adherence | No for rejection episodes |
| Knobel 1999 | HIV | Zidovudine + lamivudine + indinavir PLUS individualized counselling/assessments which consisted of adaptation of treatment to the patient's lifestyle and detailed information about highly active antiretroviral therapy (n = 60) | Zidovudine+ lamivudine + indinavir plus conventional care (n = 120) | Yes | Yes for reduction of viral load. No for detectable viral load. |
| Kunutsor 2011 | HIV | TREATMENT SUPPORTER INITIATIVE: Patients in the TS arm received both the TS intervention and the standard adherence intervention package. Elements of the standard intervention package consisted of self monitoring of medication taking using adherence diaries; regular individual and group education by peer‐workers using patient education leaflets and tabletop flip‐charts; and late attendee tracing. The treatment supporters were usually family members—usually a partner, mother, daughter, sister, brother, friend, or neighbor/friend—who were chosen by the patient with the assistance of the health workers, had accepted the patient's HIV status and were confidantes. These individuals were committed to support the patient with ART for a long time, had gained the patient's trust over time, and commanded respect. Patients were asked to bring their chosen treatment supporter to the ART clinic for the health worker to explain about ART, adherence and treatment support. This includes commitment, confidentiality, knowledge on HIV and ART related needs, and perhaps emergency resource needs such as money, help with household, and children. Treatment supporters were educated with the following WHO Integrated Management of Adolescent and Adult Illness (IMAI) educational materials: Patient Education Flipchart, Patient Education Cards, and Caregiver Booklets. They were also educated on how to remind the patient to take their medicine, be present at the follow‐up appointments, remember all important test results and clinic history over time, and to accompany patient to support group meetings if possible. Treatment supporter meetings were also held at the clinic every 2 or more weeks to deal with issues of burn out, patient non‐adherence and other barriers to treatment and adherence | STANDARD ADHERENCE INTERVENTION: Patients randomized to the control arm did not have a treatment supporter but otherwise received the same standard adherence intervention package including the ongoing existing health education and adherence counseling support that all patients received during routine monthly clinic visits. These existing interventions are typical for HIV/ AIDS treatment programs in Uganda and the rest of sub‐Saharan Africa | No for mean adherence. Yes for proportion of patients who were at least 95% adherent | No for clinical attendance. No for number of deaths |
| Lai 2011 | Post‐menopausal osteoporosis | PHARMACIST COUNSELING: The intervention was enhanced pharmacist care. Patients were followed over a 12‐month period that included 4 visits. All participants were given a 3‐month supply of their drugs at each visit, and instructed on how to take their medications. Intervention participants received an explanation on osteoporosis, risk factors, lifestyle modifications, goals of osteoporosis therapy, side effects and the importance of medication adherence. Verbal counseling was reinforced with an osteoporosis booklet. The pharmacist also reviewed participant's medications and conducted monthly follow‐up via telephone calls for the first 6 months, then every 3 months until month 12 | USUAL CARE: Participants were dispensed 3 months' supply of bisphosphonate and instructed on how to take their medications. Received no counseling | Yes for improving adherence based on pill counts at 6 months. Yes for improving adherence based on self recording at 6 and 12 months. No for all other adherence outcomes | No for bone turnover markers at 3 and 6 months |
| Laporte 2003 | Compliance and stability of international normalized ratio (INR) of 2 oral anticoagulants with different half‐lives | The standard education group received the minimum information consistent with ethical oral anticoagulant therapy (OAT) with no particular emphasis on the necessity of strict compliance. Patients in the intensive education group received information about the causes of anticoagulation instability and the importance of strict adherence. The intensive education group were provided information through visual material, were visited daily by nurses and physicians to repeat some items, and were tested daily about their education. The education, either standard or intensive, was given until hospital discharge | A 2 by 2 factorial design with patients randomly allocated to warfarin (long half‐life, n = 43) or acenocoumarol (short‐half life, n = 43) and to either intensive education (n = 43) or standard education (n = 43) | No | No |
| Larrey 2011 | Genotype 1 hepatitis C | NURSE EDUCATION: The nurse used a standardized questionnaire to evaluate the patient's understanding of the disease and the side effects of treatment. The nurse responded to any questions and informed the patient as thoroughly as possible with the means at his/her disposal, including by using explanatory texts and drawings. The nurse's goal during the consultation was to improve adherence. The following points were systematically covered: a) evaluation of the reasons for any eventual change in adherence; b) improvement of the quality of the patient‐medical team relationship; c) explanation of para‐clinical tests on therapeutic follow‐up and discussion of the positive aspects of the results; d) facilitation of the quality of the patient's relationship with his/her family and/or professional milieu; e) increasing if necessary social service support for the patient. This consultation with the nurse took place in a standardized fashion, which was set out in a document to guide the consultation. All the nurses involved in these consultations had received prior training in the field of viral hepatitis and its treatment, and on the details of this study. The consultation lasted between 30 and 45 minutes. At the end of the consultation, the nurse filled out a standardized questionnaire build for this study and comprising 34 items in 8 groups The patient could call the nurse free‐of‐charge if necessary outside the standard consultation dates | USUAL CARE: The control group received conventional clinical follow‐up. These patients did not receive consultation from the nurses | No for improving adherence | Yes for improving virological response |
| Lee 2006 | Hypertension and hyperlipidemia | Comprehensive pharmacy care program consisting of 3 elements (n = 83): individualized medication education; medications dispensed using blister packs; follow‐ups every 2 months by clinical pharmacists | Usual care (n = 76); followed a 6‐month comprehensive care period; patients were then given a 90‐day supply of their medications with one repeat) | Yes | Yes for systolic blood pressure. No for diastolic blood pressure and LDL‐C |
| Lester 2010 | HIV | SMS GROUP: All intervention group participants were given brief training about the use of SMS intervention by the study clinicians. On Monday morning of each week, the site nurse or clinical officer sent a text message via SMS to patients in the intervention group to inquire about their status and thus to remind them about the availability of phone‐based support. Regular, structured mobile phone communication between healthcare workers and patients could improve patient outcomes by both reminding patients to take their ART and by providing support to the patients. Patients in the intervention group were instructed to respond within 48 hours that either they were doing well or that they had a problem. The clinician then called patients who said they had a problem or who failed to respond within 2 days. Participants were instructed that healthcare workers were available to respond during clinic hours only | USUAL CARE: Control group is standard care. Standard care at Kijaiado study site included providing 1 counseling session at ART initiation and at the 2 Nairobi sites included providing 2 counseling sessions before and 1 session 1 month after ART initiation. Disclosure of HIV status, pairing up with a treatment adherence partner, and participation in support groups was encouraged but not insisted upon. Additional brief counseling was provided at each site during dispensation of the drugs in the clinic or pharmacy. Patients did not receive weekly SMS | Yes for improving adherence to ART medication at 6 and 12 months | Yes for viral loads at 12 months |
| Levy 2000 | Acute asthma | 1‐hour structured asthma consultation with study nurse 2 weeks after entry into study, followed by 2 or more 30‐minute consultations at 6‐weekly intervals (n = 103) | Usual care (n = 108) | Yes for use of inhaled topical steroids and rescue medication for severe attacks. Not statistically significant for use of inhaled topical steroids and rescue medication for mild attacks | Yes |
| Maitland 2008 | HIV/AIDS | ONCE DAILY DOSING (QD): Patients were switched to a fixed‐dose combination tablet of ABC and 3TC dosed once a day. All other antiretroviral agent(s) in the patient's regimen were dosed once a day from or before screening | USUAL DOSING (TWICE A DAY): Patients remained on ABC and 3TC twice a day. All other antiretroviral agent(s) in the patient's regimen were dosed once a day from or before screening | Yes for adherence at 4 weeks | No for viral load at 4 weeks. No for HAD at 4 weeks |
| Margolius 2012 | Hypertension | HOME TITRATION GROUP: Clinicians of patients in the home titration arm completed an algorithm of antihypertensive medication adjustments. Health coaches made weekly telephone calls to participants in both study arms to discuss overall well‐being, adherence to action plans, and blood pressure values. Patients in the home titration arm who reported blood pressure greater than 140 mm Hg systolic or greater than 90 mm Hg diastolic and excellent medication adherence could choose to increase their antihypertensive medication regimen according to the algorithm without a clinician appointment. In those cases, health coaches notified a physician investigator to fax the prescription to the pharmacy. Clinicians were notified of medication changes by e‐mail, and health coaches entered the change in the electronic health record. The duration of the intervention was 6 months | NO HOME TITRATION: Home monitoring and health coaching alone (no home titration arm), included health coaches made weekly telephone calls to participants in both study arms to discuss overall well‐being, adherence to action plans, and blood pressure values. The duration of the intervention was 6 months | No for adherence at 6 months | No for blood pressure at 6 months. No for change in number of primary care office visits |
| Marquez Contreras 2004 | Hypercholesterolemia | The intervention group (IG) of 63 patients received the standard care given to control group, and in addition received a telephone call at 7 to 10 days, 2 months, and 4 months. The goal of the intervention was to establish the level of compliance, categorize this as adequate or inadequate, and make recommendations based on that. Level of compliance was determined by comparing the number of pills consumed to the number that should have been consumed (calculated using self reported information about the number of pills remaining, number of pills dispensed, and fill date of the prescription). Compliance was defined as taking 80% to 110% of the pills that should have been taken thus far. Compliant patients were congratulated and encouraged to continue their good level of compliance as it would lower their risk of heart disease. Non‐compliant patients were notified their behavior was considered non‐compliant and encouraged to better comply with therapy as it would lower their risk of heart disease | The control group (CG) of 63 patients, who received the doctor's normal treatment, which included oral information about hypercholesterolemia, advice about its control, brochures about dietary recommendations, 3 month‐long prescriptions for a cholesterol‐lowering medication, and titration of that medication if indicated at 3 months | Yes | Yes for the 6‐month decrease in total cholesterol and LDL‐C was significantly different between IG and CG (Table 3). No for the 6‐month decrease in triglycerides and HDL‐C |
| Marquez Contreras 2005 | Hypertension | 2 intervention groups (both receiving routine primary care plus 1 of): 1) Telephone intervention (TIG; n = 216) ‐ Patients received 3 telephone calls (15 days, 2 months, 4 months) by nurse to reinforce compliance and remind them of scheduled visits. The nurse gave feedback about compliance based on patient self report of pills consumed. 2) Mail intervention (MIG; n = 212) ‐ Patients received 3 mailed communications (15 days, 7 weeks, 15 weeks) to promote compliance through education in hypertension, medication compliance, and reminders of scheduled visits | Routine primary care for hypertension (n = 212) | Yes for pill count in both intervention groups in comparison to the control group | Yes for blood pressure control in both the TIG and the MIG in comparison to the control group. Yes for both SBP and DBP at 6 months for both the TIG and the MIG when compared to the control group. Yes for both SBP and DBP reduction from baseline to 6 months in the TIG in comparison to the control group |
| Marquez Contreras 2006 | Hypertension | Usual care plus OMRON automatic monitor for home blood pressure monitoring (HBPM), a card to record pressures, with an instruction book and phone call to go over instructions (n = 100) | Usual care in a primary care setting at 40 sites (n = 100) | Yes | No for all clinical outcomes except the change in diastolic blood pressure from baseline to 6 months between groups |
| Marquez Contreras 2007 | Hypercholesterolemia | CALENDAR REMINDER: The patients in the intervention group were mailed a calendar as a reminder of medication taking. The calendar is double sided. On one side, there is a calendar where the patient can make with an x the days of the months when they should be taking their medication. On the other side, there is information about the next visits, treatment recommendations and a place to insert lipid analysis info | USUAL TREATMENT: Patients received treatment as usual as provided by a family physician | Yes for adherence to lipid medication | Yes for cholesterol count at 24 weeks. Yes for triglyceride count at 24 weeks. No for HDL‐C count at 24 weeks; Yes for LDL‐C count at 24 weeks |
| Martins 2009 | Tuberculosis | FOOD INCENTIVE: The intervention was a food incentive program in which the intervention group patients were provided with midday meals every time they attended the clinic. Patients were to report to the clinic 5 or 6 mornings a week to receive directly observed treatment in the intensive phase and fortnightly in the continuation phase | NUTRITIONAL ADVICE: Control participants received usual care. They were also given nutritional advice (verbal and written) about the types of locally available food that would constitute a balanced diet and would be likely to assist cure of tuberculosis | No for improvement of adherence in patients receiving directly observed treatment for TB with food incentives | No for completion of treatment. No for symptoms. No for cough clearance. Yes for weight gain |
| Matsumura 2012 | Hypertension | COMBINATION PILL: The intervention was a combination pill instead of multiple pills. Patients assigned to the intervention group received a combination pill (losartan 50 mg/hydrochlorothiazide 12.5 mg). Follow‐up was done at 1, 3, and 6 months | MULTIPLE PILLS: Control patients were provided with an angiotensin receptor blocker and a diuretic. Follow‐up was done at 1, 3, and 6 months. Adherence outcomes and blood pressure were measured at the 1, 3, and 6‐month appointments; patient outcomes at before and 6 months after randomization | No for improving adherence to medication at 1, 3, and 6 months in patients with hypertension | No for improving blood pressure at 1, 3, and 6 months in patients with hypertension. No for difference in adverse events and blood variables (hematocrit, serum creatinine, serum sodium, serum potassium and serum uric acid) observed in 2 groups |
| Mehuys 2011 | Type 2 diabetes | COMMUNITY PHARMACIST INTERVENTION: Patients in the intervention group received pharmacist‐led, individual education about type 2 diabetes and its complications, education about the correct use of oral hypoglycemic agents, facilitation of medication adherence, healthy lifestyle education (diet, physical exercise, and smoking cessation), and reminders about annual eye and foot examinations. These elements were implemented at the first visit and at each prescription‐refill visit of the patient during the 6‐month intervention period | USUAL PHARMACIST CARE: Patients in the control group received usual pharmacist care | No for adherence to oral hyperglycemics with high refill rates and self reported adherence in both groups | Yes for reduction in HbA1c. No for FPG. Yes for FPG and HbA1c in high risk group (FPG > 10.7) |
| Merinder 1999 | Schizophrenia | 8‐session psychoeducational program for schizophrenic patients and their relatives, conducted using a mainly didactic interactive method (n = 23) | Usual treatment provided in community psychiatry (n = 23) | No | Yes for knowledge of schizophrenia and for VSSS subscore satisfaction with relatives' involvement. There was also a trend towards reduced BPRS score in intervention group (P value = 0.07). No for time to relapse or insight into psychosis or psychosocial function (GAF) |
| Morgado 2011 | Essential hypertension | PHARMACIST INTERVENTION PROGRAM: In sessions at baseline (30 minutes) and 3 and 6 months follow‐up (20 minutes) the clinical pharmacist thoroughly interviewed the patient to identify problems with medication adherence, provided patient education and counseling, and provided advice to physicians regarding pharmaceutical care. Pharmacists could schedule additional visits as needed, and patients were encouraged to bring all empty medication blisters and boxes to visits | USUAL CARE: Control group patients received usual care through the hospital clinic. Pharmacists were not involved in their care | Yes for improving adherence to antihypertensive medication at 9 months | Yes for patient knowledge of target BP values. Yes for proportion of patients achieving BP control. Yes for reduction in baseline SBP and DBP |
| Morice 2001 | Asthma | Subsequent visits from the asthma nurse until discharge from hospital (n = 35) | 'Routine care' from medical and nursing staff but no further intervention from the asthma nurse (n = 30) | No (on the contrary, medication compliance of beta‐agonist inhaler in intervention group was lower than in control group) | No for the total occasions of GP call‐out and re‐admission. Yes for patients percentage of claiming to have a writing management plan and self management |
| Moshkovska 2011 | Ulcerative colitis | PERCEPTUAL (MOTIVATIONAL) INTERVENTIONS: Participants who were assigned to the intervention group attended a one‐on‐one education and motivation session conducted by the researcher. First, this session aimed to identify perceptual and practical barriers to 5‐ASA medication adherence and, second, to motivate, convince, and educate. The session was designed as a structured dialog allowing the patient to comment and ask questions. Educational topics included ulcerative colitis, 5‐ASA medication, and adherence. Participants were also encouraged to identify practical barriers to 5‐ASA medication use, as well as perceived barriers to adherence. Strategies for overcoming these barriers were also discussed. Sessions lasted for 20 to 30 minutes and were intended to deliver individualized support to each patient. At the end of the session patients were offered an educational leaflet to take away. Patients had the option of being accompanied to these educational sessions by a relative or friend and any accompanying person was also offered a leaflet specifically written for relatives and friends. During the session patients were offered a free choice of up to 3 practical adherence enhancing interventions; simplifying of dosing regime, medication reminder charts, visual medication reminders for refrigerators and bedside cabinets, daily electronic pill box organizers with alarms, weekly electronic pill box organizers, weekly non‐electronic pill box organizers, mobile telephone alarm set‐up, taking into consideration that practical problems and adherence may change over time. Participants had the option of changing these interventions at any time during the study and at weeks 4 and 24 they were formally asked whether they wished to change the interventions. 1 brief follow‐up telephone call was made to patients in the intervention group at week 4. During the mid‐study visit a 10‐minute reinforcement session was held during which the importance of adherence to prescribed 5‐ASA medication was reiterated, beliefs regarding medicine‐taking were reassessed, and any practical problems were discussed. All intervention group patients were given a telephone number which enabled them to obtain advice at specified times or leave a message for a return call | USUAL CARE: Patients in the control group received standard prescribed care from their clinical team. The treatment regime for these patients was not changed in any way as a result of involvement in the study and no reminders or other additional adherence support was offered by the research team. Participants in the control group provided 3 urine samples at 0, 24, and 48 weeks and completed questionnaires during baseline and end‐of‐study visits. At the end of the study, control group participants were given the educational leaflets that intervention group participants received at the beginning of study. | Yes for improving adherence to 5‐ASA at 12 months to reduce the risk of disease flare‐ups. | No difference for disease flare‐ups at 12 months. |
| Mullan 2009 | type 2 diabetes mellitus | DIABETES MEDICATION CHOICE DECISION AID TOOL: The intervention was the use of a decision aid tool in one appointment with the patient. The tool is designed to enable clinicians to discuss with patients the potential advantages and disadvantages of adding an agent from 1 of the following antihyperglycemic classes to their regimen: metformin, insulin, thiazolidinediones, exenatide, and sulfonylureas. The tool consists of 6 cards that describe the possible effects of the medications on 6 outcomes: "Weight Change," "Low Blood Sugar," "Blood Sugar," "Daily Routine," "Daily Sugar Testing," and "Side Effects". After reviewing and discussing the cards that the patient and the clinician choose to discuss, they arrive at the medication that best matches the patient's circumstances and preferences. The patient receives a copy of the cards in the form of a take‐home pamphlet. | USUAL CARE: Participants in the usual care arm discussed anti‐hyperglycemic medication in the usual manner. In addition, patients received a professionally produced (by the Mayo Clinic Patient Education Center) 12‐page general pamphlet on oral anti‐hyperglycemic medications to take home | Yes for adherence judged by pharmacy records. Yes for self reported adherence | No for HbA1c levels |
| Muniz 2010 | Acute coronary syndrome | POST DISCHARGE EDUCATIONAL INTERVENTION: Intervention is an educational intervention consisting of a signed agreement between patient and physician on the objectives to be reached. The intervention includes a personalized interview at discharge with patient and nearest next‐of‐kin, in which physician and patient discuss and sign an agreement with the patient‐specific secondary prevention procedures and therapeutic aims. Both physician and patient keep a copy of the signed agreement. Written back‐up information (about heart attack, controlling cholesterol, body weight, and blood pressure, and effects of smoking), and a phone number as to where to call in case of questions were given. Intervention also included an interview with the patient 2 months after discharge in order to review the agreement, adapt treatment if needed, and reinforce the intervention. Informative materials are given once again.The visits took an average of 30 to 40 minutes each. | USUAL CARE: Control group participants received usual care. Follow‐up was at 6 months | Yes for significant difference between intervention and control groups at 6 month for improving adherence to statins. No for difference between intervention and control groups for medication adherence to aspirin, clopidogrel, beta‐blockers, ACE‐inhibitors, and Angiotensin receptor blocking agent Type II at 6 month | Yes for reduction in BMI. Yes for reduction in lipid level and waist circumference at 6 months in intervention group with an educational program at discharge following acute coronary episode. No for blood pressure control |
| Murray 2007 | Heart failure | PHARMACIST INTERVENTION: A pharmacist delivered the intervention by using a protocol that included a baseline medication history of all prescription and over‐the‐counter drugs and dietary supplements taken by patients, which patients brought with them to the baseline interview, and the results of an assessment of patient medication knowledge and skills. The pharmacist dispensed enough of the patient's medications to last approximately 2 months. The intervention lasted 9 months. When medications were dispensed, the pharmacist provided patient‐centered verbal instructions and written materials about the medications. Each medication category had an icon associated with it. The same icon appeared on the container label and lid and on the written patient instructions. The pharmacist monitored patients' medication use, health care encounters, body weight, and other relevant data by using a study database. Information about patients was communicated as needed to clinic nurses and primary care physicians by face‐to‐face visits, telephone, paging (physician only), and e‐mail (physician only). An interdisciplinary team of investigators trained the intervention pharmacist. The intervention pharmacist also studied guidelines for treating heart failure, key concepts in the pharmaceutical care of older adults, communication techniques, and the pharmacotherapy of the cardiovascular drugs for heart failure | USUAL CARE: Control groups received usual care. Usual care participants were aware of the purpose of the study. They received their prescription services from the same pharmacy as the intervention participants, but the pharmacists who attended the usual care participants were not trained by the interdisciplinary team | Yes for adherence based on MEMS and pharmacy refill records. No for self reported adherence | Yes for exacerbations. No for improving the quality of life in heart failure patients receiving pharmacy intervention at 6 and 12 months compared to usual care |
| Nazareth 2001 | Complex regimens in the elderly (aged 75 years and older on 4 or more medicines who had been discharged) | The hospital pharmacist developed discharge plans which gave details of medication and support required by the patient. A copy was given to the patient and to all relevant professionals and carers. This was followed by a domiciliary assessment by a community pharmacist. (n = 165) | In the control group, patients were discharged from hospital following standard procedures that included a discharge letter to the general practitioner listing current medications (n = 151) | No | No |
| Nguyen 2008 | Gastrointestinal irritability due to prenatal multivitamins | SMALL LOW IRON DOSE TABLET: Small low dose iron tablets were used as the intervention in this study. PregVit a prenatal multivitamin that contains 35 mg elemental iron, as ferrous fumarate was prescribed for intervention group patients. The multiple vitamins and minerals are formulated into 2 small tablets, and is taken as 2 tablets per day. After enrolment, subjects received a 1‐week follow‐up telephone call and then were interviewed by telephone on a monthly basis until the end of pregnancy. Each interview documented obstetrical and medical information, adherence based on pill intake recall, and any reported adverse events. The date(s) of discontinuation at any time(s) during study participation was documented as the date(s) reported by the subject during the monthly interview | SMALL 60 MG MULTIVITAMIN TABLET: A small‐sized high‐dose (60 mg) multivitamin administered once daily was used as the control in this study | No for improving adherence to multivitamin in pregnant women | No for reduced adverse effects in pregnant women |
| Nieuwkerk 2012 | Increased cardiovascular risk | EXTENDED CARE: Subjects in Extended Care (EC) received multifactorial risk‐factor counseling, in addition to Routine Care (RC). During the counseling the nurse practitioner explained the presence of unmodifiable risk factors, such as age, gender, and family history, and modifiable risk factors, such as lipid levels, diabetes mellitus, blood pressure, overweight, smoking habits, and physical activity. The study nurse was not blinded to the purpose of the study. The counseling focused on changing modifiable risk factors such as increasing medication adherence, reducing overweight, smoking cessation, and increasing physical activity. All obtained data were summarized in a personal risk‐factor passport: a graphical presentation of the patient's calculated 10‐year cardiovascular disease risk. It also showed the target risk that could be reached if all the patient's modifiable risk factors were optimally treated, as well as the standard age‐ and gender‐related risk. 10‐year risk and target risk were calculated using the Framingham risk score. The risk‐factor passport contained the most recent ultrasound image of the patient's carotid artery, as well as an example of a healthy and an unfavorable image of the carotid artery, which were both explained and discussed by the nurse practitioner. This risk‐factor passport was updated during each follow‐up visit | ROUTINE CARE: Routine care consisted of measuring body weight and blood pressure and performing a capillary lipid profile at each visit. Initially, all participants received atorvastatin 10 mg, unless baseline cholesterol levels were severe and more aggressive therapy was needed. Dose escalation during the study period was allowed if deemed appropriate by the treating physician | Yes for improving adherence to lipid‐lowering medication in patients with increased cardiovascular risk | Yes for lowering the low‐density lipoprotein cholesterol, improving intima‐media thickness and anxiety. No for improving body weight, body mass index, blood pressure, adverse events and quality of life |
| O'Donnell 2003 | Schizophrenia | The experimental group (n = 28) received 5 sessions of compliance therapy, each session lasting 30 to 60 minutes. The sessions covered a review of the patient's illness history, understanding of the illness and his or her ambivalence to treatment, maintenance medication and stigma. Compliance therapy is a cognitive behavior intervention with techniques adapted from motivational interviewing, other cognitive therapies and psychoeducation | The control group (n = 28) received non‐specific counseling comprising of 5 sessions lasting 30 to 60 minutes | No | No |
| Odegard 2005 | Poorly controlled type 2 diabetes, on oral medications | Usual care (see Control) plus: Pharmacist‐led intervention (n = 43): Pharmacist‐patient communication on diabetes progress; pharmacist‐provider communication on the subject's progress; medication‐related problems ‐ the pharmacists were not formally affiliated with the clinic | Usual care (primary care, university‐based, medical clinics) (n = 34) | No | No for all clinical outcomes |
| Ogedegbe 2012 | Hypertension | POSITIVE AFFECT INTERVENTION: Patients in the Positive Education (PE) control group received a culturally tailored educational workbook designed (1) to enhance patients' knowledge about hypertension, (2) to improve self management behaviors, and (3) to support goal‐setting. Patients randomized to the Positive Affect (PA) intervention group were given the same workbook as those in the PE group but with an additional chapter that addresses the benefits of positive moments in overcoming obstacles to medication adherence. Also, these patients received 2 forms of PA during bimonthly telephone calls. First, they were asked to identify small things in their lives that invoke positive feelings in them and were then instructed to incorporate these positive thoughts into their daily routine. The positive thoughts were further reinforced during subsequent bimonthly telephone calls. Second, the patients received unexpected small gifts mailed to them before each telephone call. This strategy was based on the potential of the receipt of unexpected gifts to induce positive feelings. For self affirmation induction, the patients were asked to remember their core values and proud moments in their lives whenever they encounter situations that make it difficult for them to take their medications | PATIENT EDUCATION: Patient Education (PE) control group received a culturally tailored educational workbook designed (1) to enhance patients' knowledge about hypertension, (2) to improve self management behaviors, and (3) to support goal‐setting. On receipt of the workbook, trained Research Assistants (RAs) reviewed each chapter with the patients and then asked them to sign a behavioral contract that asked them to make a commitment to taking their medications as prescribed. Subsequent to this session, each patient received bimonthly telephone calls, during which the RAs assessed the patient's behavioral contract and confidence to take their medications as prescribed. These assessments served as the basis for reviewing and counseling the patient on perceived barriers to medication adherence. The intervention lasted for 12 months | Yes for improving adherence to medication at 12 months | No for reducing systolic and diastolic blood pressure at 12 months |
| Okeke 2009 | Glaucoma | INTERVENTION: The intervention consisted of 4 components. (1) a 10‐minute educational video created through Alcon, Inc. marketing branch for the DA device, which stressed the importance of regular drop‐taking, its rationale and expected effects, alternatives to eyedrops, and methods to maximize co‐operation, such as linking drops to a daily activity, keeping a drop‐taking calendar diary, and using family members to help in reminding them; (2) a structured discussion with the study co‐ordinator to develop a strategy for improving adherence that included finding the best time of day to take the medication, distributing a blank calendar diary and going over details of how to keep it, and discussing individual patient barriers to taking the medication; (3) reminder telephone calls from the co‐ordinator, including administration of a questionnaire about drop‐taking behavior, difficulty with drops, side effects, and eliciting questions about therapy (this call was made once per week for the first follow‐up month and then every other week for the next 2 months); and (4) activation of the audible and visible alarms on the DA | USUAL CARE: Usual care group were told that it is important to take their eyedrops as prescribed but had no other intervention | Yes for improving eyedrop adherence at 6 months | No for lowering intraocular pressure between 3 and 6 months |
| Otsuki 2009 | Asthma | ASTHMA BASIC CARE (ABC): ABC intervention received 5 30‐ to 45‐minute home visits by trained asthma educators (AEs) 1, 2, 3, 4, and 8 weeks after randomization. The ABC intervention is a home‐based asthma education program with 5 core components: (1) review of the prescribed asthma regimen and training in medication, spacer, and peak flow technique; (2) development of an asthma action plan; (3) identification of barriers to accessing health care and problem‐solving to reduce barriers; (4) discussion of beliefs and concerns about asthma and medications; and (5) provision of written asthma education materials | USUAL CARE: Patients received an asthma education booklet and resource guide that provided information about low‐cost asthma care providers, social services, legal services, and other resources. Participants were encouraged to receive care from their primary care provider | Yes for pharmacy refills both AMF versus UC and Combined intervention group versus UC were significant but declined after active intervention was removed. No difference for ABC versus UC or AMF versus ABC. No for self report | Yes for reduction of ED visits between AMF and UC group. No for reduction in oral corticosteroids between AMF and UC groups. No for asthma symptom frequency and hospitalizations between AMF and UC group. No for reduction of ED visits between ABC and UC groups. Yes for improvement in asthma symptom frequency between ABC and UC groups. Yes for decrease in oral corticosteroid use between ABC and UC group. No for hospitalization rate between ABC and AMF groups. No for improvement in any clinical health outcome between AMF and ABC group. Yes for ED visit reduction and use of oral corticosteroids between combined intervention groups and UC group. No for asthma symptom frequency and hospitalization between combined intervention groups and UC |
| Parienti 2007 | HIV | ONCE A DAY DOSING: Patients were switched from 2 a day nevirapine to a 1 a day formula | TWICE A DAY DOSAGE: Control participants continued to take nevirapine twice a day | No for adherence rates. Yes for increased monthly days without dose. No for monthly drug holidays | No for viral control |
| Parsons 2007 | HIV | PROJECT PLUS INTERVENTION: Intervention was 8, 60‐minute individual sessions based on Information Motivation Behavioral Skills model delivered by delivered by master's degree–prepared counselors. 2 complementary techniques—motivational interviewing (MI) and cognitive‐behavioral skills training (CBST)—were integrated, allowing trained counselors to match targeted information and skill‐building techniques to the particulars of each client's motivation for change.The first session was delivered immediately on completion of the baseline assessment, thereby ensuring that each participant has a minimum dose of 1 session. Follow‐ups were conducted at 3 and 6 months | EDUCATION CONDITION: 8 education sessions of 60 minutes facilitated by a health educator was the intervention. Sessions were designed to be completed weekly, but participants had 12 weeks to complete all 8 sessions. The first session was delivered immediately on completion of the baseline assessment, thereby ensuring that each participant had a minimum dose of 1 session. The sessions were video taped to ensure that motivational interview or cognitive‐behavioral skills training was not used | Yes for improving percentage dose adherence and percentage day adherence at 3 months. No for improving percentage dose adherence and percentage day adherence at 6 months | Yes for reducing viral load and increasing CD4 count at 3 months. No for reducing viral load at 6 months and No for increasing CD4 count at 6 months |
| Pearson 2007 | HIV | PEER DELIVERED MODIFIED DIRECTLY OBSERVED THERAPY (MDOT): The participants in the MDot intervention group received both the standard of care and a 6‐week peer intervention to monitor their morning weekday dose. Peers also provided daily social support, information about the benefits and side effects of HAART, and help to address barriers to adherence. Peers were also a link between participants and other members of the HIV clinic team and the community | STANDARD CARE: Includes no‐cost medications, clinical and laboratory follow‐up, psychosocial adherence support by a trained social worker, and referral to community‐based peer support groups. Mandatory pre‐HAART counseling involves education about dosing, side effects, nutritional requirements, and the importance of adherence. Patients were encouraged to identify a treatment partner to help with adherence, provided with information on community‐based support groups and nutritional resources, and instructed to contact their medical provider, nurse, pharmacist, or peer if they have any difficulties or concerns about their medication regimen. Peers were HIV‐positive, chosen from among patients at the clinic and participants in community‐based groups through self nomination or nominations by clinic staff, and were paid a small stipend for their work. Patients met with the pharmacist and peer for pharmacy refills at week 2, 4, and 6 for the first 2 months and monthly thereafter | Yes for improving 7‐ and 30‐day adherence at 6‐ and 12‐month follow‐up | No for mean CD4 cell count at 6 and 12 months. No for mortality rate at 6 months |
| Perrin 2010 | Asthma | COMBINATION METERED DOSE INHALER (MDI): Subjects received the intervention treatment regimen for a duration of 24 weeks that involved 125 mg FP and 25 mg salmeterol in a combination Smartinhaler, 2 actuations twice daily. Participants were seen in the clinic on 5 occasions. At the first visit, subjects were randomized and issued the appropriate Smartinhalers, and inhaler technique was checked. Subjects were instructed to take 2 actuations of the study medications twice daily, resulting in a daily dose of 500 mg FP and 100 mg salmeterol with both regimens. Subjects were advised that the study was designed to compare the efficacy of the 2 regimens but were not informed that adherence would be monitored. They were told that the MDI casing looked different because it was possible to program it with a reminder alarm, but that this function would not be used in this study | SEPARATE METERED DOSE INHALER (MDI): Subjects received a treatment regimens for a duration of 24 weeks of 125 mg FP and 25 mg salmeterol in separate Smartinhalers, 2 actuations twice daily. Participants were seen in the clinic on 5 occasions. At the first visit, subjects were randomized and issued the appropriate Smartinhalers, and inhaler technique was checked. Subjects were instructed to take 2 actuations of the study medications twice daily, resulting in a daily dose of 500 mg FP and 100 mg salmeterol with both regimens. Subjects were advised that the study was designed to compare the efficacy of the 2 regimens but were not informed that adherence would be monitored | No for improving compliance during the final 6 weeks of the study, for the first 3 6‐week periods, percentages of days that subjects were adherent, or for the proportion of subjects who took > 50%, 80%, or 90% of their prescribed inhaler medication | No for Asthma Control Questionnaire score and lung function (FEV1) |
| Peterson 1984 | Epilepsy | Counseling, leaflet, self monitoring of pill‐taking and seizures, mailed reminders for appointments and missed drugs refills | Usual care | Yes | No |
| Peterson 2004 | Dyslipidemia | Patients in the intervention group (n = 45) were visited at home monthly by a pharmacist, who educated the patients on the goals of lipid‐lowering treatment and the importance of lifestyle issues in dyslipidemia and compliance with therapy, assessed patients for drug‐related problems, and measured total blood cholesterol levels using point‐of‐care testing | Patients in the control group (n = 49) received standard medical care. There was no further contact with patients in the control group after the initial collection of baseline data, until 6 months had lapsed. At that time, their final total blood cholesterol level was measured, and the current medication regimen and self reported compliance were recorded | No | No |
| Peveler 1999 | Depression | Treatment information leaflet (n = 53), drug counseling (n = 52) or both leaflet and counseling (n = 53) | Usual care (n = 55) | Yes for counseling (at 12 weeks). No for leaflet | No for counseling. No for leaflet |
| Phumipamorn 2008 | Diabetes | EXTRA PHARMACIST SERVICE: Patients received their usual scheduled care by a primary care physician every 4 to 8 weeks. At each visit, fasting blood glucose was checked by the laboratory. Blood pressure and weight were recorded by a qualified nurse. A research pharmacist checked the pill count. Each patient then met a physician who assessed the patient and issued a repeat or modified prescription which the dispensing pharmacist filled and they also gave general advice on the medication uses. This was done over the dispensary counter on a routine basis. In addition to the usual care, each patient of the study group had a scheduled meeting with the research pharmacist for 4 consecutive visits at 2‐month intervals. Each visit was on the same date as the physician's appointment and in addition, to avoid a missed appointment, a health personnel co‐ordinator attached to the primary health care centre in the area, where a patient was living, reminded the patients of the scheduled visit 3 days prior to each visit date. At each visit, the research pharmacist refilled prescriptions, discussed the uses of medication and checked the pill count. Education on diabetes which included appropriate lifestyles and correct diet was also provided apart from a companion diabetic pamphlet which covered the diabetic complications, the targets of treating diabetes, lifestyle change, and antidiabetic medications | USUAL CARE: The control group received their usual scheduled care by a primary care physician every 4 to 8 weeks. At each visit, fasting blood glucose was checked by the laboratory. Blood pressure and weight were recorded by a qualified nurse. A research pharmacist checked the pill count. Each patient then met a physician who assessed the patient and issued a repeat or modified prescription which the dispensing pharmacist filled and they also gave general advice on the medication uses. This was done over the dispensary counter on a routine basis | Yes for improving adherence to medication in Muslim diabetic patients | No for A1C. Yes for change in total cholesterol. No for changes in triglycerides. Yes for change in LDL. Yes for change in HDL. No for change in non HDL |
| Portsmouth 2005 | HIV | Participants were assigned to take Stavudine (d4T), which is a prolonged‐release once‐daily formulation of a thymidine‐based nucleoside reverse transcriptase inhibitor (NRTI). Both groups continued their other medications | Participants in the control group were assigned to continue the twice daily version of d4T (IR/3TC/EFV or Combivirs/EFV) as per their screening regimen | No for all adherence outcomes | No for all clinical outcomes |
| Powell 2010 | Heart failure | SELF MANAGEMENT PLUS EDUCATION: In the self management plus education treatment, patients received group base heart failure education plus counseling to help patients develop mastery in problem‐solving skills and in 5 self management skills. 18 2‐hour group meetings of approximately 10 patients were spread over the course of 1 year. At each meeting, education in the form of 18 heart failure tip sheets summarized basic elements of patient management. A problem‐solving format was used. Groups were led by health professionals | EDUCATION ONLY: Patients randomized to receive education received the same 18 Heart Failure Tip Sheets, on the same schedule as the self management group meetings but delivered by mail. To ensure receipt and check comprehension, a study co‐ordinator contacted the patient by telephone within 2 to 3 days of each mailing. If the tip sheet had not been read, the call was rescheduled. All questions about the tip sheets were answered. For concerns unrelated to the tip sheets, the patient was referred to his or her primary care clinician | No for adherence in patients with mild to moderate heart failure | No for reduction in death or heart failure hospitalization in patients with mild to moderate heart failure. Yes for decreased major depressive symptoms, restricting sodium intake with time (2 to 3 years). No for difference in NYHA class, 6‐minute walk, heart rate, respiratory rate, blood pressure, body mass index, quality of life, emotional support, or purpose in life |
| Powers 2011 | Coronary heart disease and stroke | PERSONALIZED RISK COMMUNICATION: Patients in the personalized risk communication arm received standard risk factor education (control) as well as personalized information based on their Framingham CHD and stroke risk score, presented verbally and in graphic form as vertical bar charts. Patients' average and optimal CHD and stroke risks based on published estimates for their 5‐year age group were also presented in graphical form alongside their estimated risk. To achieve optimal risk, patients were presented with potential strategies to improve their risk through risk factor modification such as medication and patient lifestyle factors. A copy of the patient's personal risk information was also provided to the primary care provider | STANDARD RISK FACTOR EDUCATION: Control patients received written patient education materials from the American Heart Association/American Stroke Association entitled "Are You at Risk of Heart Attack or Stroke?" which reviewed risk factors and how these factors can be improved but did not provide personalized estimates of individual risk. The research assistant verbally reviewed the information with all patients and answered any questions at the initial visit | No for improving medication adherence with personalized stroke risk communication in coronary heart disease patients | No for risk factor knowledge, beliefs and health behaviors, or estimated vascular risk |
| Pradier 2003 | HIV | Patients (n = 100) in the intervention group (IG) were offered 3 individual sessions by trained nurses. | No mention was made of the care that was provided for the control group (n = 102). | Yes | No. The clinical significance of these findings is unclear ‐ adherence rate was on self report in an unblinded trial, the mean HIV RNA was no different at 6 months for the 2 groups and no actual clinical outcomes were reported. |
| Purcell 2007 | HIV with injection drug use | PEER MENTORING INTERVENTION: The peer mentoring intervention sessions were delivered twice a week for 5 weeks and included 7 group sessions, 2 individual sessions, and 1 ''peer volunteer activity'' (PVA), during which participants went to a local service organization for 2 to 4 hours to observe, participate, and practice peer mentoring skills. The first session focused on setting group rules and the power of peer mentoring, 2 group sessions and 1 individual session focused on utilization of HIV primary care and adherence, and 3 group sessions and 1 individual session focused on sex and drug risk behaviors. Risk messages were communicated using posters and handouts with risk hierarchies that helped to form individualized risk plans discussed during the individual session focusing on sex and injection behaviors. The final group session focused on review and reinforcement of motivation and skills for behavior change and ended with a graduation ceremony. For both treatment groups, a resource table that provided information about local services available for medical care, support groups, drug treatment, and prevention resources such as pamphlets and male and female condoms was available during and after every session | VIDEO DISCUSSION INTERVENTION: Control participants had similar access to general information resources and risk reduction information and resources Intervention participants, and received equal attention during the study regarding groups sessions, but not the 2 individual sessions as for Intervention. Participants in the Control group took part in 8 group sessions over 5 weeks. For all but session 1, the Control sessions were led by the same 2 facilitators who led the Intervention sessions. Participants in the Control group watched documentary or self help videos focused on issues relevant to HIV‐positive intravenous drug users, followed by facilitated discussion. Topics directly related to the intervention outcomes were avoided or minimized. Community resources and risk reduction information and tools were available at every Control session | No for improving the proportion of patients adherent with HIV therapy after 12 months | No for reduction in hospital utilization, sexual risk behavior, and injection drug risk behavior with a peer mentoring intervention |
| Pyne 2011 | HIV with depression | HIV TRANSLATING INITIATIVES FOR DEPRESSION INTO EFFECTIVE SOLUTIONS (HITIDES): The purpose of the HITIDES intervention was to support HIV and mental health clinicians in delivering evidence‐based depression treatment. The HIV depression care team consisted of a registered nurse depression care manager, a clinical pharmacist, and a psychiatrist. This team was located offsite and convened once a week and as needed by telephone or in person. The depression care team communicated with treating clinicians via electronic medical record progress notes. The DCM communicated with patients via telephone. The HITIDES depression care team made treatment suggestions. Treatment decisions were made by the HIV or mental health clinicians at each site. The DCM delivered the following intervention components: participant education and activation, assessment of treatment barriers and possible resolutions, depression symptom and treatment monitoring, substance abuse monitoring, and instruction in self management. The DCM used prewritten scripts, which are standardized instruments that were supported by the Web‐based decision support system during these telephone encounters. The intervention used a stepped‐care model for depression treatment. At any time, HIV health care providers were free to refer participants directly to specialty mental health care. The DCM conducted telephone‐based monitoring every 2 weeks during acute treatment and every 4 weeks during watchful waiting or continuation treatment. The NetDSS system identified potential treatment non‐response as (1) antidepressant regimen adherence of less than 80% during the past 14 days, (2) counseling non‐adherence of less than 75% during the past month, (3) participant report of severe adverse effects during 2 consecutive DCM encounters, (4) participant report of a 5‐point increase in depression severity from the enrollment PHQ‐9 score based on 2 consecutive DCM encounters, or (5) lack of participant response during an 8‐week antidepressant or 12‐week counseling trial | USUAL CARE: Usual care depression treatment was provided by HIV or mental health clinicians without involvement of the HITIDES depression care team. Before starting the study, all HIV health care providers received 1 hour of HIV and depression training | No for improving adherence to antidepressant medication regime. No for improving adherence of HIV medications | No for reduction of depression severity score. No for improvement in health‐related quality of life. Yes for treatment response improvement at 6 months. Yes for intervention effect in remission rates at 6 months. No for treatment response at 12 months. No for remission rates at 12 months. Yes for depression free days |
| Rawlings 2003 | HIV | 4 modules of the Tools for Health and Empowerment HIV education intervention (EI) plus routine counseling (RC) | Routine counseling alone (RC) | No | No |
| Razali 2000 | Schizophrenia | Culturally modified family therapy (CMFT), which consists of a sociocultural approach of family education, drug intervention program and problem‐solving skills | Behavior Family Therapy (BFT) | Yes | No at 6 months. Yes at 12 months for all variables (exacerbation, GAF score, SBS score, rehospitalization, family burden) |
| Remien 2005 | HIV | Usual care (see Control) plus a 4‐session (45 to 60 minutes each, over 5 weeks), couple‐focused adherence intervention consisting of treatment and adherence education, identifying adherence barriers, developing communication and problem‐solving strategies, optimizing partner support, and building confidence for optimal adherence, with each partner receiving USD 20 for each session attended | Usual care from a multidisciplinary treatment team, including monthly visits with provider if nonadherent | No | No for all clinical outcomes |
| Rickles 2005 | Depression | Usual care (see Control) plus: Pharmacist‐guided education and monitoring (PGEM) ‐ to address concerns, educate, and help patients increase adherence to medication | Usual care ‐ no special counseling or monitoring of adherence | No for all adherence outcomes | No |
| Riesen 2008 | Primary hypercholesterolemia | 10 MG PLUS: Patients received a daily oral treatment with rosuvastatin and access to compliance enhancement tools (10 mg Plus group) for 24 weeks. Patients were assessed at week 4 and at week 12 to review fasting levels of TC, LDL‐C, HDL‐C, and triglycerides. For patients not achieving the 1998 European target for LDL‐C at week 12, the daily dose of rosuvastatin was increased to 20 mg for the remainder of the study. Patients in the 10 mg Plus group received a starter pack containing a videotape and educational leaflets concerning their condition. These patients also received newsletters at regular intervals and had access to both a telephone helpline and an Internet website, all designed to reinforce the initial message in the starter pack | 10 MG: Patients received a daily oral treatment with rosuvastatin alone (10 mg group) for 24 weeks. Patients were assessed at week 4 and at week 12 to review fasting levels of TC, LDL‐C, HDL‐C, and triglycerides. For patients not achieving the 1998 European target for LDL‐C at week 12 the daily dose of rosuvastatin was increased to 20 mg for the remainder of the study | No for improving adherence to rosuvastatin medication at 12 and 24 weeks | Yes for reducing low‐density lipoprotein cholesterol level at 24 weeks below 3.0 mm/mol (European 1998 goal) and not below 2.5 mm/mol (European 2003 goal). No for reducing total cholesterol and plasma lipid levels at 12 and 24 weeks. No for changes in heart rate, blood pressure, and body weight at 24 weeks |
| Rosen 2007 | HIV | CONTINGENCY MANAGEMENT: The intervention group participants were provided with 16 weeks of weekly CM‐based counseling followed by 16 additional weeks of data collection and adherence feedback to providers followed by 16 additional weeks of data collection and adherence feedback to providers. The CM intervention provided by bachelor's level staff involved review of data generated by electronic pill‐bottle caps that record bottle opening (MEMS) and brief substance abuse counseling. CM participants were reinforced for MEMS measured adherence with drawings from a bowl for prizes and bonus drawings for consecutive weeks of perfect adherence | SUPPORTIVE COUNSELING CONDITION: The supportive counseling condition was an attention control condition. Participants were encouraged to meet with counselors weekly. In these sessions, participants were asked about their adherence, and offered support for their efforts to improve adherence. However, the counselors did not review MEMS data with the participants or conduct urine toxicology testing. There was an initial review of self reported substance abuse and referral to available treatment. In addition, providers were sent monthly letters stating the participant's self reported adherence. The same staff members delivered both interventions | Yes for improving adherence to reinforced antiretroviral therapy during the intervention period (1 to 16 weeks) but no during the follow‐up period (17 to 32 weeks). No for improving adherence to non‐reinforced antiretroviral therapy during the intervention and follow‐up period | Yes for reducing viral load at 16 weeks but not at 32 weeks. No for reducing the viral load below 400 HIV‐RNA copies per milliliter at 16 and 32 weeks |
| Rubak 2011 | Type 2 diabetes | MOTIVATIONAL INTERVIEWING: The courses in "motivational interviewing" (MI) for the GPs in the intervention group were conducted by a trained teacher introducing a manual which together with "Motivational interviewing, preparing people to change addictive behaviour" constituted the theoretical part of the course curriculum. The intervention group was coached in the key points of MI. The training also included the use of specific skills, e.g. empowerment, ambivalence, the decisional balance schedule, the visual analogue scale, stage of change, and reflective listening, all of which are described in detail in the book MI. The intervention group courses consisted of a 1½ ‐day training sessions with a half‐day follow‐up twice during the first year. None of the GPs in I‐ and control group had previously participated in an MI course. All GPs in the I‐ and the control group participated in the same half‐day course on intensive treatment of type 2 diabetes. During these diabetes training sessions, it was stressed that GPs should act as counselors for the patients, allowing treatment decisions to be based on mutual understanding between the patient and the GP. In Denmark, GPs' consultation encounters average 15 minutes and the County Health Insurance has agreed to one longer preventive consultation encounter of 45 minutes per patient. In this study the County Health Insurance agreed to allow the GPs in the I‐ and control group to undertake 3 consultations of 45 minutes per patient, in which the intervention group could use MI | CONTROL: None of the GPs in the control group had previously participated in an MI course. All GPs in the control group participated in the same half‐day course on intensive treatment of type 2 diabetes. During these diabetes training sessions, it was stressed that GPs should act as counselors for the patients, allowing treatment decisions to be based on mutual understanding between the patient and the GP. In Denmark, GPs' consultation encounters average 15 minutes and the County Health Insurance has agreed to one longer preventive consultation encounter of 45 minutes per patient. In this study the County Health Insurance agreed to allow the GPs in the control group to undertake 3 consultations of 45 minutes per patient. | No for improved adherence to blood glucose‐lowering drugs, BP or lipid‐lowering drugs at 1 year in type 2 diabetes patients | Yes for improved blood pressure, blood lipid measurement, HbA1c, and BMI at 12 months in both controls and intervention groups. No for improvement in blood pressure, blood lipid measurement, HbA1c, and BMI in intervention group compared to control groups |
| Rudd 2004 | Hypertension | A nurse care manager conducted baseline counseling on the correct use of the automated blood pressure (BP) device, regular return of the automatically printed BP reports, tips for enhancing adherence, and recognition of drug side effects; the nurse phoned patients at 1 week, 1, 2, and 4 months. The nurse changed doses on own and called physician for medication changes (n = 74) | Usual care (n = 76) | Yes | Yes for changes in both systolic and diastolic blood pressure from baseline to 6 months between groups |
| Sabin 2010 | HIV/AIDS | COUNSELING BASED ON ELECTRONIC DRUG MONITORING DATA: When intervention participants came to the clinic monthly, a study member downloaded and reviewed the subject's previous month's electronic drug monitoring device (EDM) data. Each subject found to be less than 95% adherent according to the EDM data was 'flagged' for counseling with a clinic physician or nurse utilizing the EDM information immediately following regular clinic visit activities. The data were provided to both the subject and his/her clinician as a printout summarizing the percent of doses taken, the percent of doses taken on time, and a visual display of doses taken by time. This process of flagging and counseling was specific to each clinic visit. In each counseling session, the clinician reviewed the EDM printout with the subject, explored reasons for missed or off‐time doses, and inquired about problems or challenges the subject might be having. Beyond this, counseling sessions did not follow a script. This was designed to accommodate each clinician's counseling style, allow for an individually‐focused discussion of adherence behavior, and encourage each subject‐clinician pair to devise personalized strategies to improving adherence. In this regard, the EDM feedback provided data to inform and thereby enhance the counseling, but did not dictate precisely how the counseling should be performed. In the event that subjects did not immediately offer reasons for missed or off‐time doses, clinicians were advised to say: "Let's talk more about any problems that you had last month".' Most counseling sessions were completed within 10 to 15 minutes. The intervention period was 7 to 12 months | STANDARD CARE: Control group participants provided their electronic drug monitors (EDM) data at their monthly visits to the study team members and received standard care. Standard care in China included completing self reports of adherence and attending counseling session with clinician if self reported adherence indicated less than 95% adherence. In the counseling sessions with control subjects, which were guided by self reported adherence and clinicians inquired about recent problems that might have affected dose‐taking | Yes for improving adherence to ART at 12 months in the intervention group | No for improvement in markers of HIV progression with electronic drug monitoring based counseling in HIV positive patients in China |
| Sackett 1975 | Hypertension | (a) Care at work site by occupational health physicians (n = 37); (b) Detailed 'programmed' instructions about hypertension and adherence (n = 28); (c) Both a and b (n = 44) | Neither intervention (n = 25)* * numbers provided by author | No | No |
| Sadik 2005 | Heart failure | Usual care plus: Booklets and education on heart failure (HF) and training on a self monitoring program (daily weights and symptom diary, to share with physician and pharmacist; extra dose of diuretic if weight rose). Research pharmacist interacted with physicians to simplify drug regimens, with patients on follow‐up visits to clinic | Usual care in a medical or cardiology clinic | Yes | Yes for 2‐minute walk test, blood pressure and pulse, HF symptoms, forced vital capacity and both quality of life measures ‐ the MLHFQ and SF36 |
| Samet 2005 | HIV | Usual medical care plus nurse‐led intervention (60 minute session + 3 follow‐up visits) with 4 parts (n = 74): a) assessment of the alcohol and substance use b) a watch to time medications and improve adherence c) enhancement of perceived efficacy of medications d) individualized HIV counseling | Patients received regular medical care for HIV infection. This included verbal or written instructions about optimal medication strategies | No | Yes for CD4 count |
| Sarna 2008 | HIV | MODIFIED DIRECTLY OBSERVED THERAPY (M‐DOT): Patients in the intervention arm received M‐DOT services for the first 24 weeks of ART, in addition to standard care. Although consideration was given to provision of home‐based M‐DOT, formative research revealed that patients were concerned this would undermine their privacy and confidentiality. They also believed that clinic visits would provide beneficial access to health care workers, so M‐DOT services were provided during twice weekly clinic visits. To enhance convenience, participants could select 1 of 6 health centers for their M‐DOT visits. At each visit, participants met with M‐DOT observers (nurses) who observed ingestion of the patient's ART dose, inquired about difficulties encountered, and provided individualized adherence support. Used medication containers were also collected, pill counts recorded, and medication dispensed for the subsequent 3 or 4 days. During the monthly clinic visits, efforts were made to ensure that participants in the M‐DOT and control group received equal contact time with study staff to minimize the likelihood that any differences observed would be due to nonspecific effects of increased attention given to the intervention group. CHW traced M‐DOT participants who missed visits and brought medications to participants who were unable to visit the facility. After cessation of M‐DOT at week 24, patients had no further contact with M‐DOT observation centers. Like the control group, they collected monthly medication refills at recruitment clinics and received standard adherence support during weeks 25 to 72. No compensation was given for study participation, though travel costs were reimbursed for 21 M‐DOT participants with financial constraints (USD 0.65 per visit) | STANDARD CARE: As standard care, all participants attended 3 one‐on‐one adherence counseling sessions before initiating ART. In these, trained nurse counselors emphasized the importance of adherence; educated patients on the treatment regimen, dosing instructions, side effects, and dietary considerations; tailored the regimen to daily activities; and identified social issues like living conditions and family support. After ART initiation, patients visited treatment centers every 4 weeks for follow‐up. At the first 2 follow‐up visits, general adherence counseling was provided, as was discussion of specific emerging problems with side effects or medication intake; thereafter, counseling was tailored to individual needs. All patients were encouraged to bring a family member or friend to clinic visits and counseling sessions | Yes for 24‐week adherence. No for 48 and 72‐week adherence | No for suppression of viral load at 48 weeks. No for increase in CD4 cell count and immunological improvements. Yes for larger mean increase in BMI during the intervention period |
| Schaffer 2004 | Asthma | (a) Audiotape alone (n = 10); (b) National Heart Lung and Blood Institute (NHLBI) booklet alone (n = 12); (c) Audiotape plus NHLBI booklet (n = 11) | Standard provider education (control) (n = 13) | Yes for positive effect on adherence by pharmacy‐refill measure for booklet versus control, and for booklet + audiotape versus control, but not for audiotape versus control, at 6 months. No for self reported adherence | No |
| Schroeder 2005 | Hypertension | Usual care (see Control) plus nurse‐led adherence support sessions (20 minutes initially, 10 minutes 2 months later) with the following goals (n = 128): patients address problems with blood pressure lowering medication; explain diagnosis and the treatment process; address patient concerns with their medication and tailor strategies to resolve any problems | Usual care at their doctors' practices, other than blood pressure checks at similar intervals as the intervention group (n = 117) | No for all adherence outcomes | No for all clinical outcomes |
| Sherrard 2009 | Adverse events post‐cardiac surgery (coronary bypass grafts/valvular surgery) | INTERACTIVE VOICE RESPONSE (IVR): Patients in the IVR follow‐up group received automated telephone calls for 6 months, at 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, and 24 weeks after discharge. The telephone interview contained an algorithm of 11 questions addressing medication compliance, reporting of adverse events, providing information on common medications, and offering general medication safety tips. The intent of the IVR algorithm was to provide early identification of issues permitting timely intervention, provide a mechanism for tracking medication compliance, and provide medication information at the time deemed most valuable by the patient at his or her request and to provide longer‐term follow‐up as the patient transitioned from hospital to home. Patients were asked questions about medication compliance such as, "Did you fill the prescriptions given to you at discharge?" and were offered additional information on 8 common medications prescribed to cardiac surgical patients on discharge. The answers to the questions were captured in a database. Depending on the response, a colored flag appears in the database next to the question indicating no action is needed, the call was not answered, or alerting the nurse to intervene by calling the patient to provide education and counseling | USUAL CARE: Patients in the control group received the standard of care provided to all patients discharged from post‐cardiac surgery. This included receiving an IVR call on day 3 and 10 after discharge to screen common symptoms. This current surgical follow‐up algorithm does not contain questions or information on medications. They were contacted at 6 months to answer questions on medication compliance and outcomes | Yes for improving compliance at 6 months in IVR group compared to UC in post‐cardiac surgery patients | Yes for composite outcome. No for ER visits and hospitalizations |
| Simon 2011 | Depression | CARE MANAGEMENT: Intervention group received care management intervention in addition to usual care by the treating physician. The intervention was delivered online but the structure was similar to the telephone programs tested in earlier studies. After randomization, participants received a welcome letter describing the program and it contained general advice about the antidepressants medication and self care for depression. Monitoring contacts were scheduled 2, 6, and 10weeks later. At each monitoring contact, there was an outreach message from the nurse containing a link to an online assessment. The assessment included the PHQ depression questionnaire and questions regarding use of antidepressant medication, side effects, and reasons for medication discontinuation. Those not responding were sent up to 2 reminder messages. For each assessment completed, an algorithm generated a suggested response based on PHQ depression score, current antidepressant use, and side effects. The care manager could tailor this suggested response using information in the medical record or in messages since the last contact. The care manager communicated with the treating physician using an electronic messaging system within the electronic medical record. In consultation with the physician, the care manager might facilitate follow‐up visits, support changes in medication, or facilitate referral for specialty care (including urgent referrals in case of suicidal ideation or severe symptoms). Each of the 3 care management contacts included this cycle: outreach message from the care manager, patient completion of online assessment, structured response from the care manager, and follow‐up communication with the patient and physician as needed. The care manager's messages to patients included brief support but no formal psychotherapy. Patients were free to send additional messages or telephone the care manager if needed. The care manager was expected to make outreach telephone calls in case of suicidal ideation or other urgent clinical need. All outgoing messages were in English. The care manager in this trial was a registered nurse with added certification in psychiatry and 15 years of experience in mental health | USUAL CARE: Controls received usual care and did not receive any additional care other than what was normally available, which included follow‐up in primary care or specialty referral for psychotherapy or medication management. Online patient‐provider messaging was available to all patients in the usual care | Yes for increasing use of antidepressant over 90 days for patients with depressive disorder | Yes for improving SCL depressive scores and satisfaction with depression treatment. No for increased hospitalization or suicide attempts |
| Simoni 2007 | HIV/AIDS | PEER SUPPORT: Patients in the peer support group had 6 twice‐monthly meetings during the 3‐month peer support intervention where peers and participants met with other peers and participants to discuss shared experiences, barriers to HAART adherence, life issues, etc. The group meetings were facilitated by an RA but were predominately peer‐led. Between group meetings, peers were instructed to call each of their study participants 3 times weekly to provide more in‐depth one‐on‐one attention and feedback | STANDARD CARE: Standard of care (control) patients received no additional adherence assistance beyond the clinic's typical offerings (consultation with primary providers and social and mental health referrals when requested) | No for medication adherence by self report and EDM at 3 and 6 months | No for HIV‐1 RNA viral load and depressive symptomatology |
| Simoni 2009 | HIV/AIDS | PEER SUPPORT: The 3‐month peer support intervention consisted of 2 parts: (a) 6 twice monthly 1‐hour gatherings held at the clinic, consisting of all peers and actively enrolled participants in the peer support arm and (b) weekly phone calls from peers to participants. At the time of enrollment, participants were assigned to individual peers by study staff based on peer availability and presumed compatibility. In the group setting, participants had the opportunity to interact face‐to‐face with their assigned peer and meet the other peers and participants, with the goal of benefiting from the discussion of the shared experiences of the group. The meetings were designed to identify barriers to HAART adherence and generate problem‐solving strategies to overcome them. Other emerging themes included life issues that impact adherence, including HIV status disclosure, dating, substance use, and struggles with mental health issues. One of several research staff members coordinated the groups by making reminder phone calls, preparing the meeting room, and providing refreshments. With assistance from the peers, they facilitated the meetings by refocusing the discussion on adherence‐related topics when appropriate. Otherwise, they refrained from interfering with the group process and the exchange of support among peers and participants, resulting in predominantly peer led groups. Participants received a $15 incentive for attending each of the 6 sessions. All were welcomed to continue attending thereafter but were provided neither reminder phone calls nor monetary incentives for additional meetings. Between group meetings, peers were instructed to call each of their study participants weekly to provide more in‐depth one‐on‐one attention and feedback. Phone calls also were better suited for participants with confidentiality concerns and those who had difficulty traveling to the clinic or had scheduling conflicts with the set meeting times. Peers were instructed not to initiate contact with participants after the 3‐month intervention period, but they were allowed to respond to requests for contact from the participants at their own discretion 56 participants in Pager Messaging and Peer Support | USUAL CARE: Before initiation of HAART, all clinic patients who are naive patients or off HAART for more than 6 months are required to complete the HAART protocol, a clinic‐based program designed to provide education regarding HAART and adherence and to identify and correct adherence barriers before HAART initiation. The HAART protocol involves a series of 3 separate appointments with a pharmacist, nutritionist, and case manager after an initial meeting with a provider and before a final meeting when the provider decides whether to prescribe HAART. During these preliminary interviews, patients are given social and mental health referrals as appropriate, a daily medication schedule, and information on medication side effects and techniques to help manage them. All participants in each of the study's 4 arms participated in the HAART protocol if they had not received it in the last 6 months. There were no time or attention‐control activities | Yes for improving self reported adherence at 3 month in peer intervention. No for improving self reported adherence at 6 and 9 months. No for improving EDM adherence for peer intervention at 3, 6, or 9 months. No for improving self reported and EDM adherence at 3, 6, and 9 months in pager intervention | No for improvements in viral loads and CD4 cell counts at 3, 6, or 9 months in the peer intervention arm or pager intervention arm |
| Simoni 2011 | HIV/AIDS | ENHANCED INTERVENTION ARM: Patients assigned to the intervention arm could choose an alarm device, counseling or both. The alarm device was either a cell phone (if the patient so chose) or a small battery powered electronic alarm device. In either case, the project staff helped the patient set up the device of their choice. Counseling was delivered by a bachelor level nurse. In accordance with a manualized protocol, the counseling sessions involved a cognitive‐behavioral and problem‐solving approach to: (1) enhancing motivation for treatment continuation, (2) learning about antiretroviral medication and the prescribed regimen, (3) keeping appointments, (4) communicating with healthcare providers, (5) formulating a daily medication schedule, (6) storing medications, (7) setting reminder strategies, (8) coping with side effects, (9) securing family and social support, (10) handing adherence lapses, and (11) addressing additional barriers. Participants could also invite a treatment partner to attend the counseling sessions with them. A ''treatment partner'' was defined as someone to whom the participant had already disclosed their HIV status and who was available to assist the participant on a daily basis. Participants who opted to have counseling, either individually or with a treatment adherence partner, had 3 counseling sessions of up to 1 hour each with the study nurse. The first session occurred either at the enrollment interview or within the first 2 weeks of initiating ART; additional counseling sessions occurred at 5 and 9 weeks. If necessary, the later sessions were replaced with counseling provided over the telephone | MINIMAL INTERVENTION ARM: At the baseline appointment and before initiation of ART, all participants completed a 1‐hour interviewer‐administered paper‐and‐pencil baseline survey. They then participated in a 30‐minute educational session facilitated with a flip‐chart, which was designed to provide information regarding their treatment plans, likely side effects, and the importance of adherence. All patients also were given a daily medication schedule, a plastic pill box to organize daily doses, and a referral card to the hospital‐based peer support group. Participants assigned to the minimal intervention were to receive no further adherence‐promotion intervention beyond the usual care at the clinic, which involved monthly medication pick‐ups and any conversations patients initiated with their healthcare providers. All participants continued to receive medical care as usual at the clinic | Yes for improving self reported 7‐day adherence and dichotomous 30‐day adherence at 19 weeks. No for improving self reported or EDM based adherence at 7, 13, and 25 weeks | No for improvement in viral load and CD4 cell count at 13 and 25 weeks |
| Sirey 2010 | Major depression | TREATMENT INITIATION AND PARTICIPATION PROGRAM (TIP): The Treatment Initiation and Participation Program (TIP) included 3 30‐minute individual meetings between the TIP counselor and older adult patient during the first 6 weeks of pharmacotherapy, followed by 2 follow‐up telephone calls at 8 and 10 weeks after study entry. During these sessions the TIP counselor and older adult would review symptoms and antidepressant therapy regimen, and conduct a barriers assessment, define a personal goal that could be achieved with adherence, provide education about depression and antidepressant therapy, collaborate to address barriers to treatment participation, create an adherence strategy and facilitate and empower the older adult to talk directly with the PCP about the treatment. A "contact sheet" listed barriers in each domain and specific intervention techniques and served as the guide for sessions and a record of the interventions administered | TREATMENT AS USUAL (TAU): Patients in the control group continued with treatment as usual | Yes for improved self reported adherence to antidepressant medication throughout all time points | Yes for reduction in depressive symptoms |
| Solomon 2012 | Osteoporosis | TELEPHONE BASED COUNSELING: Subjects in both groups started receiving educational material regarding osteoporosis 30 days after randomization. In addition the intervention group subjects received motivational intervening based counseling administered by a health educator. 10 sessions were targeted per subject | CONTROL: Approximately 30 days after randomization, all subjects received mailings regarding osteoporosis. During the study, all subjects received 7 informational mailings covering topics such as exercise, fall prevention, and recommended calcium intake | No for medication adherence measured using MPR during 12 months | No for self reported falls. No for poor or fair general health |
| Sorensen 2007 | HIV | VOUCHER INTERVENTION: Patients in the voucher intervention group began with a 4 week baseline phase, where they received a MEMS monitor for one of their HAART medications. Patients met with a registered nurse or trained research assistant who provided medication coaching once during the baseline phase and then every 2 weeks throughout the study. Patients were provided with a hard copy of their MEMS data throughout the study. During baseline, patients met a research assistant twice weekly to provide the MEMS data. At the end of the baseline phase, patients in the voucher phase continued to meet twice weekly with a research assistant, for a total of 24 visits. When patients opened their medication caps as scheduled, they received vouchers that were exchangeable for goods and services for each correctly taken medication dose. The value of the voucher increased for each correctly taken dose in a row, but reset to the original value if a dose was missed. Patients could earn up to USD 1172.40 if they took all their medication correctly throughout the study | COMPARISON: Patients in the comparison group began with a 4‐week baseline phase, where they received a MEMS monitor for one of their HAART medications. Patients met with a registered nurse or trained research assistant who provided medication coaching once during the baseline phase and then every 2 weeks throughout the study. Patients were provided with a hard copy of their MEMS data throughout the study. During baseline, patients met a research assistant twice weekly to provide the MEMS data. During the intervention phase, comparison group participants continued to meet twice weekly with the research assistant, for a total of 24 visits, and received medication coaching every 2 weeks. As several of the initial comparison group participants expressed dissatisfaction with their treatment compared to the voucher group, a reward system was implemented for the comparison group. A fishbowl prize system was used to reinforce attendance at scheduled interviews. Patients could pick a number from the fishbowl which would give them either a small or large prize | Yes for improving adherence while intervention was active. No for maintaining that adherence during the follow‐up phase | No for all patient health indices |
| Staring 2010 | Psychotic disorders | TREATMENT ADHERENCE THERAPY: Initial sessions assess individual determinants of non‐adherence. According to the clusters of determinants detected, therapists fill out a decision form and chose from the 3 modules available for the subsequent patient appoints. Modules are motivational interviewing, medication optimization, and behavioral training. If more than one cluster of problems was present in an individual, the modules were completed in order. The duration and number of sessions varied per patient, in general taking no more than 6 months. Most of the therapists were psychiatric nurses who were not the patients own mental health professionals. All sessions were recorded and used in supervision | TREATMENT AS USUAL: Treatment as usual generally consisted of sessions with a psychiatric nurse and a psychiatrist when indicated. The sessions varied in frequency and duration, but mostly consisted of one or 2 sessions per month. The contents reflected overall problems the participant might encounter such as symptoms, social participation, work, daily activities, and medication issues. Some participants received psychoeducation individually or in group sessions. This was recorded | Yes for improving adherence to antipsychotic medications in the intervention group at the end of intervention and at 6‐month follow‐up | No for decrease in hospital admissions and improvement in symptoms and quality of life for participants in TAT group compared to controls at 6‐month follow‐up |
| Stevens 2002 | Helicobacter pylori | A longer adherence counseling session and a follow‐up phone call from the pharmacist during drug treatment (n = 163). All subjects were given the same 7‐day course of omeprazole, bismuth subsalicylate, metronidazole, and tetracycline hydrochloride (OBMT) | A standard antibiotic regimen and randomly assigned to receive usual care counseling from a pharmacist (n = 162). All subjects were given the same 7‐day course of omeprazole, bismuth subsalicylate, metronidazole, and tetracycline hydrochloride (OBMT) | No | No. (The big problems with this study are that a) both groups got blister packs with daily doses clearly marked; b) both groups got counseling, although this was longer and more detailed for the IC than CG; c) self report was used for measuring adherence (insensitive). All these factors would bias towards no difference) |
| Strang 1981 | Schizophrenia | Family therapy (n = 17) | Individual supportive therapy (n = 15) | Yes | Yes |
| Taiwo 2010 | HIV | TREATMENT PARTNER INTERVENTION: In addition to standard care, patients randomized to the treatment partner intervention (TPA) arm chose a treatment partner who was aware of the patient's HIV infection and resided in the same house or in close proximity. Treatment partners attended one adherence education session similar to that for study participants. They were asked to observe the ingestion of HIV drugs at least once daily, assist with the reporting and management of adverse effects, and remind participants of drug pickup. No compensation was provided for participation, but treatment partners with financial constraints received travel stipends of USD 2–14 (total) | STANDARD CARE: All participants were given a 2‐hour interactive adherence session in English and local language conducted by a nurse who was openly HIV positive trained as adherence counselor. Content included information on ART, HIV drug resistance, symptom management, and emphasis on the importance of adherence and benefits of disclosure. Each patient was given a pillbox and educated on proper use. The study pharmacist, who was blinded to treatment arm, provided one‐on‐one reinforcement of the education provided by the adherence counselor plus information specific to each participant's regimen. The pharmacist had formal training in adherence counseling and more than 3 years experience at study clinic. At each drug pickup visit, the pharmacist provided targeted counseling based on the participant's self report of adherence and adverse effects. Patients who had detectable viremia at week 24 underwent intensive adherence retraining with the adherence counselor. This retraining was aimed at identifying individualized obstacles to adherence and practical tips for overcoming them. Follow‐ups were conducted at 12, 24, and 48 weeks after baseline | Yes for improving medication adherence in HIV patients undergoing ART with Treatment Partner Intervention at 12 and 48 weeks | No for viral load of HIV, CD4 count, or mortality |
| Tuldra 2000 | HIV | Psychoeducative intervention to implement adherence, i.e. explanations about reasons for starting treatment and the relevance of appropriate adherence, development of a dosage schedule with patients' input, patients were taught how to manage various other aspects of medication taking in highly active antiretroviral treatment (HAART) (i.e. forgetting, side effects, changes in daily routine). Phone number was given should patients have any questions before next interview. Verbal reinforcement of adherence at follow‐up visits | Usual medical follow‐up | No | No |
| Udelson 2009 | Chronic HF and left ventricular (LV) dysfunction | ONCE DAILY DOSING: The intervention was an open‐label, once daily regimen of controlled release carvedilol CR | TWICE A DAY DOSAGE: Participants received their usual twice daily dose of carvedilol IR, but in a double‐blinded fashion | No for improving adherence to carvedilol in patients with HF and LVF with simplified dosing | No improvement in quality of life (QOL), PHQ‐8 Depressive Symptoms Questionnaire (PHQ‐8), and Treatment Satisfaction Questionnaire with Medication. No for BNP levels and hospital and emergency services utilization |
| Valencia 2007 | Schizophrenia | PSYCHOSOCIAL SKILLS TRAINING (PSST): PSST is psychosocial skills training. It is composed of 7 treatment areas: (1) symptom management, (2) medication management, (3) social relations, (4) occupational, (5) money management, (6) couple relations, and (7) family relations. A therapist's manual describes all the areas, the skills corresponding to each area, and the training strategies for each session. The trainers were 2 psychologists who used 6 learning activities to teach patients skills acquisition: (1) introduction and explanation of the skills to be taught, including preparing and motivating patients to participate actively in the learning activities; (2) demonstration of the skills by one of the therapists, followed by a question‐and‐answer segment that allowed for clarification; (3) role playing: patients practiced the skills by role playing during sessions; (4) role playing feedback to allow patients to identify the resources needed to perform the skills in the real world; (5) practice of skills in their natural environment; and (6) at the beginning of the following session a segment was dedicated to verifying the practice of the skills in the community; this information was registered in a skills learning check‐up list. The learning activities were similar to the 7 instructional techniques proposed for teaching social and instrumental skills to the severely mentally ill. These were modified to 6 learning activities for the participants of the present study. Patients participated in group sessions, 8 patients per group, with a time limit of 1 hour 15 minutes, once a week for a total of 48 sessions during 1 year of PSST. To verify that each treatment area was being covered systematically and adequately, a therapist fidelity evaluation form was used. Family therapy (FT) consists of 2 parts: the first was psychoeducation, which included 8 group sessions where all the patients' relatives received information about the illness, symptoms and medication management. The second part consisted of 4 sessions for each family, including the patient, oriented to problem‐solving as needed by each family to improve communication skills, the recognition and management of warning signs of relapse, the importance of medication and its side effects, compliance with AP medication, and keeping appointments with physicians. 2 family therapists conducted the FT. Recreational activities for the patients, conducted by an arts teacher, included singing, musical games, creative movement, and arts and crafts, once a week for 2 hours. Recreational activities were not considered as a therapeutic modality | TREATMENT AS USUAL: Control group was treatment as usual, which was provided at the Schizophrenia Clinic of the INPRF by 2 clinical psychiatrists, who were blind to the 2 treatment conditions.They provided 20‐minute monthly appointments during a 1‐year period, controlled the prescription of their AP medication based upon the assessment of their psychotic symptoms, checked their medication compliance, recorded their attendance to the consultations, and registered all this information in their clinical files | Yes for improving adherence to antipsychotic medication at 12 months in patients with schizophrenia | Yes for improvement in symptomatology, psychosocial and global functioning, reducing relapse, rehospitalization and dropout rates |
| Valenstein 2011 | Serious mental illness (SMI) including schizophrenia, schizoaffective and bipolar disorders | MEDS‐HELP INTERVENTION: A composite intervention consisting of: 1) unit‐of‐use packaging that included all patients' medications for psychiatric and general medical conditions; 2) a medication and packaging education session; 3) refill reminders mailed 2 weeks before scheduled refill dates; and 4) notification of clinicians when patients failed to fill antipsychotic prescriptions within 7 to 10 days of a fill date. The medication education session was conducted by a pharmacist, usually in‐person, but occasionally by telephone. During this session, the pharmacist reviewed patients' prescribed medications, including treatment indications. The pharmacist also explained unit‐of‐use medication packaging and plans for interim use of pill boxes when medication changes were made by clinicians before the next shipment of medication packages | USUAL CARE: Usual care was treatment in Veterans Affairs outpatient mental health clinics and included psychiatrist visits, non‐MD mental health visits, and group visits. During the study period, patients completed an average of 8 visits with psychiatrists; 49% had visits with non‐MD mental health clinicians and 23% had group visits | Yes for improving the medication possession ratio (MPR) of antipsychotic drugs among patients with serious mental illness | No for improving psychological symptoms, quality of life, patient satisfaction, and reducing hospitalizations at 6 and 12 months in patients with serious mental illness |
| van der Meer 2009 | Asthma | INTERNET‐BASED SELF MANAGEMENT: An internet based self management program consisting of a specially designed website which allowed monitoring through the website or text messaging, use of an internet‐based treatment plan, online education and web communications with a specialized asthma nurse was administered to the intervention group. Patients monitored their asthma weekly by completing an electronic version of the Asthma Control Questionnaire on the website and instantly received feedback on the current state of their asthma control along with advice on how to adjust their treatment according to a predefined algorithm and treatment plan. Self‐management education consisted of both web‐based and face‐to‐face, group‐based education. Web‐based education included asthma information, news, frequently asked questions, and interactive communication with a respiratory nurse specialist. All patients were offered 2 group‐based education sessions, which lasted 45 to 60 minutes, for patients in the Internet‐based self management group within 6 weeks after entering the trial. Both sessions included exploration of a patient's interests and previous knowledge, personalized feedback, and empowerment of self management. The first educational session also included pathophysiology of asthma, information on the web‐based action plan, and information and review of inhalation technique. The second educational session gave information about the mechanisms and side effects of medication and explained trigger avoidance | USUAL CARE: Website access for usual care patients was restricted to a diary page for patients to keep during assessments | No for improvement of self reported adherence with an internet‐based self management program for asthma | Yes for asthma control and lung function. No for other clinical outcomes (exacerbations, inhaled corticosteroid dose) |
| Velligan 2008 | Schizophrenia | FULL‐CAT: Cognitive Adaptation Training (CAT) uses manual‐driven compensatory strategies and supports such as pill containers with alarms, organization of belongings, and activity checklists to prompt and sequence adaptive behaviors in an individual's home environment. CAT strategies are tailored to the specific cognitive impairments and behavioral approaches to goal‐directed activity exhibited by each participant. Environmental supports in Full‐CAT treatment were based upon an assessment of neurocognitive function, behavior, adaptive functioning, and the environment. Interventions for each functional deficit were based on 2 dimensions, (1) level of impairment in executive functions and (2) whether the overt behavior of the individual during performance of goal‐directed activity was characterized more by apathy, disinhibition, or a combination of these styles. According to the CAT model, individuals with poor executive functioning need high levels of structure and more obviously placed environmental cues, while those with somewhat better executive functioning need less structure and more subtle cues. Individuals with apathetic behavior benefit from environmental supports that cue and sequence behavior, those with disinhibition benefit most from the removal of distracting stimuli, and those with mixed behavior benefit from a combination of these strategies. Assessment results yield one of 6 CAT classifications for which interventions can be targeted. Once an individual's CAT classification was determined, strategies for specific functional problems were chosen from the manual. CAT interventions were established, trained, and maintained in the home during weekly visits from a CAT therapist/trainer. Patients in Full‐CAT were seen once weekly for 30 to 45 minutes. The treatment lasted for 9 months and then the patients were followed up for 6 months after the withdrawal of home visits. CAT therapists were individuals with bachelor's or master's degrees in psychology or related fields trained using a combination of didactic and in vivo strategies. (n = 36) | TAU: Patients are seen monthly to every 3 months for brief medication visits. They have case managers with high case loads who have little ongoing contact with patients not in crisis | Yes for improving adherence in Full‐CAT and Pharm‐CAT compared to TAU throughout treatment and follow‐up. No difference between Full‐CAT and Pharm‐CAT. Yes for improving pill refill rates in Full‐CAT. No difference between Pharm‐CAT and TAU for improving pill refill rates | No for improving symptoms. Yes for increased percentage of participants with higher time to relapse in Full‐CAT and Pharm‐CAT compared to TAU. Yes for improved functional outcome in CAT compared to TAU and Pharm‐CAT at 15 months. Yes for improved functional outcome in Pharm‐CAT compared to TAU at 6 months and not thereafter |
| Vergouwen 2005 | Depression | Depression Care Program targeted both patients and their GPs. Participants received a newsletter with information about depression, the need to continue antidepressant medication for 6 months, and the importance of social support, and had homework assignments. Their GPs received newsletter summaries and copies of the homework and were to use motivational interviewing with patients | Patients and doctors did not have the program, but patient follow‐ups were scheduled at the same frequency as for the intervention group, and GPs did the same assessments for depression and compliance | No | No for all clinical outcomes |
| Volume 2001 | Ambulatory elderly (> or = 65 years of age) | Pharmacists (in n = 8 pharmacies, 159 patients) used the Pharmacist's Management of Drug‐Related Problems (PMDRP) instrument to summarize the information collected during the patient interview and the subjective, objective, assessment, and plan record to document actions and follow‐up | Pharmacists at control pharmacies (n = 8 pharmacies, 204 patients) continued to provide traditional pharmacy care | No | No |
| Wakefield 2011 | Type 2 diabetes mellitus and hypertension | HIGH‐INTENSITY GROUP: In the high‐intensity group, subjects were instructed to measure BP daily and BG as directed by their physician, that is, frequency of home BG monitoring was not changed. The study team developed a branching disease management algorithm based on DM and HTN guidelines from the VA, American Diabetes Association, and the American Heart Association. The algorithm was programmed into the device and focused on diet, exercise, smoking cessation, foot care, advice for sick days, medications, weight management, preventive care, and behavior modification and lifestyle adjustments. A schedule was established for each prompt set so that subjects received both standard prompts each day and a rotation of questions and educational content. Follow‐up was for a period of 12 months | USUAL CARE: Usual care subjects scheduled follow‐up appointments with the primary care clinic in the usual manner. Subjects had access to their nurse care manager employed by the medical center | No for improving adherence to medication in diabetes patients with hypertension with a nurse management program | Yes for decreasing A1c at 6 months. No for decreasing A1c at 12 months. Yes for decreasing SPB at 6 and 12 months in high intervention group |
| Walley 2001 | Tuberculosis | 170 were assigned DOTS with direct observation of treatment by health workers; 165 were assigned DOTS with direct observation of treatment by family members | 162 were assigned self administered treatment | No | No |
| Wang 2010 a | HIV with substance addiction | NURSE‐DELIVERED HOME VISITS: 4 home visits (every 2 months) were delivered by a qualified nurse and included 1) the provision of information about HIV/AIDS, 2) ART medication and adherence, and 3) skills to facilitate adherence, reinforcing motivation, mobilizing family support. Patients were provided with a pamphlet, electric pillbox with alarm, drug rehabilitation, methadone therapy, and stress management. In addition, tailored interventions were made based on the previous home visit and addressed barriers identified. Similarly, telephone calls were every 2 weeks including following each home visit to reinforce the effect of home visit and varied from 10 to 20 minutes to 1 hour during which adherence level, barriers and general emotional, sleeping, and eating conditions were discussed | USUAL CARE: As part of the Chinese national ART management program, patients are seen twice in the first month of ART and receive medication for half a month at each visit and in the absence of side effects and presence of normal liver and renal function, visits are reduced to once a month. The clinic's pharmacy dispenses medication monthly. Clients on ART also receive free laboratory test for CD4+ T cell counts every 3– 6 months for evaluating the effectiveness of the treatment. HIV viral load test is not routinely provided in the national treatment program because of the limited fund. The patients visit the clinic once they have side effects or other health problems and need a laboratory test. The service of home visits or phone calls from health care providers are not routinely provided | Yes for improving adherence to ART in heroin‐addicted HIV‐positive patients | Yes for improving quality of life and depressive symptoms in heroin‐addicted HIV‐positive patients |
| Wang 2010 b | Asthma | PHARMACIST COUNSELING: Patients participated in the standard nurse administered asthma education program with additional pharmacist counseling with the pharmacist. A detailed workbook prepared by chest physicians was used for each session. The asthma education program covered 4 topics taught in sequence in 3 1‐hour sessions offered during monthly clinic visits (at months 1, 2, and 3). Topics covered were: (1) definition, etiology, diagnosis, disease progress, and complications of asthma; (2) instruction to monitor disease severity, especially skills needed to use the peak expiratory flow (PEF) meter and the format to record symptoms in a diary; (3) introduction on medications for asthma therapy, including protocol of a stepwise treatment plan, pharmacology of leading asthma drugs and correct inhaler techniques; and (4) guidelines for self management, including understanding potential environmental triggers and irritant factors, environmental control and standard procedure for coping with asthma attacks. Pharmacist counseling covered information related to the action and side effects of asthma medications, treatment plans for individualized medication, and modification of medications in response to progressive asthma | CONTROL: Patients in the control group received only routine asthma care | No for improving adherence to asthma medication at 6 months | No for quality of life at 6 months |
| Weber 2004 | HIV | Intervention group participants (n = 32) received cognitive behavior therapy in addition to usual care, while control group participants (n = 28) received usual care alone. Intervention group participants were assigned to a psychotherapist and given the contact information to schedule their own first appointment. Protocol defined a minimum of 3 and a maximum of 25 sessions within the 1‐year study period. Participant and psychotherapist determined the frequency of appointments and set their own goals for future interventions | Both intervention and control groups continued to receive standard care. Standard care included monthly visits for 12 months with assessments of clinical and laboratory data, course of treatment, drug adverse events and HIV‐1 RNA | No | No |
| Weinberger 2002 | Asthma or chronic obstructive pulmonary disease (COPD) | The pharmaceutical care program provided pharmacists with recent patient‐specific clinical data (peak expiratory flow rates (PEFRs), emergency department (ED) visits, hospitalizations, and medication compliance), training, customized patient educational materials, and resources to facilitate program implementation (n = 447) | The PEFR monitoring control group received a peak flow meter, instructions about its use, and monthly calls to elicit PEFRs. However, PEFR data were not provided to the pharmacist. Patients in the usual care group (n = 303) received neither peak flow meters nor instructions in their use; during monthly telephone interviews, PEFR rates were not elicited. Pharmacists in both control groups had a training session but received no components of the pharmaceutical care intervention | Yes, for within‐group at 6 and 12 months; no for between‐group | Yes. At 12 months, patients receiving pharmaceutical care had significantly higher peak flow rates than the usual care group (P value = 0.02) but not than PEFR monitoring controls (P value = 0.28). There were no significant between‐group differences in HRQOL, but patients participating in the program were significantly more satisfied with their pharmacists than the other 2 groups |
| Wiggins 2009 | Postoperative pain after tonsillectomy and adenoidectomy | AROUND‐THE‐CLOCK INTERVENTION: The intervention was alarms to remind administering analgesic 4 hours after going to bed on the night of surgery and next 2 postoperative nights as instructed by the research nurse. In addition to the study procedure, all children and families received discharge education from their ear, nose, and throat (ENT) physician/clinic and from the professional nurses in each of the ambulatory centers. Discharge education in both ambulatory settings included use of around‐the‐clock prescribed analgesia for pain during the early days of recovery; increased fluid intake; monitoring for infection and bleeding; and returning to their specialist at a designated time in the recovery process. In addition, all ENT specialists encouraged families to contact them with concerns. All families received a phone call from a registered nurse from their ambulatory surgery center 24 hours after discharge | USUAL CARE: The usual care group (UCG) was not given any specific intervention, but was offered the same discharge education as the intervention group. Discharge education materials included information about ear pain and the length of the recovery, mothers and children expressed self doubt about their ability to provide adequate symptom management when painful experiences continued | Yes for improving adherence to analgesic in children after tonsillectomy or adenoidectomy | No for improved pain intensity and fluid intake until postoperative day 2 |
| Wilson 2010 | Asthma | SHARED DECISION‐MAKING : Session 1 involved setting the stage, gathering patient information, providing information and negotiating a treatment plan. In session 2 (1 month after session 1), and in 3 brief phone calls 3, 6, and 9 months later, patient progress was assessed and medications were adjusted, as necessary, using the assigned care management approach. Researchers used identical standardized interventionist scripts and materials. The patient's asthma history was elicited using a standardized patient information form, the patient's level of asthma control was classified, and asthma education was provided. Once treatment was negotiated, patients were instructed in the correct use of the relevant inhaler medication devices using methods previously shown by this team to improve inhaler technique and eliminate common usage errors. At the end of session 1, a written asthma management and action plan was created, and potential barriers to medication adherence were elicited and addressed using motivational interviewing techniques. Any subsequent changes made at session 2 or in a follow‐up phone call were documented in the plan. The SDM model implemented the 4 key defining features. The care manager elicited the patient's goals for treatment and relative priorities regarding symptom control, regimen convenience, avoidance of side effects, and cost. The patient was then shown a list of the full range of regimen options for all levels of asthma severity, based on the then‐current national asthma guidelines and KP pharmacopeia. These options differed with respect to the number and type(s) of medications, dosing, and schedule. Using a simple worksheet, the patient and clinician then compared the pros and cons of all of the options the patient wished to consider, which included the option of continuing the patient's current regimen to arrive at a treatment that best accommodated the patient's and care manager's goals. A SABA was always prescribed for rescue use as needed. If indicated, treatment of allergic rhinitis and/or gastroesophageal reflux disease was negotiated | USUAL CARE: Usual asthma care at KP medical centers was based on a stepped‐care approach to pharmacotherapy with the aim of long‐term asthma control, as recommended by the National Asthma Education Prevention Program's Expert Panel Report 2. At some KP sites, physicians also had the option to refer patients to an asthma care management program, typically of less than 6 months' duration, in which a licensed health professional (non‐physician) provided asthma education and addressed adherence and other medication use and self management issues in a manner similar to, but less structured than, the CDM intervention. However, asthma care management was neither a required aspect of usual care nor necessarily available at all BOAT sites, and current participation in that program was an exclusion criterion for the study. Once enrolled in BOAT, usual care and SDM or CDM patients (after the intervention phase) still had access to KP's existing care management services, if available, based on their physician's referral | Yes for improving compliance for all asthma controller medication and ICS at 1 year and no at 2 years in SDM group compared to CDM and UC and CDM compared to UC. Yes for improving compliance for beclomethasone canister equivalents in SDM group than CDM and UC at 1 year and 2 year. Yes for improving compliance to LABA use at 1 and 2 years for both SDM and CDM compared to UC | Yes for asthma‐related quality of life in both SDM and CDM compared to UC at 1 year. No for increased health care utilization in SDM and CDM than UC at 1 year. Yes for better asthma control in SDM than UC and CDM than UC. No for SABA use in SDM compared to UC and CDM at 1 year. No for SABA use in CDM compared to UC at 1 year. Yes for lung function at 1 year in SDM group compared to UC and in CDM compared to UC at 1 year |
| Wolever 2010 | Type 2 diabetes | INTEGRATIVE HEALTH (IH) COACHING: 2 coaches provided the coaching intervention. Both had substantial training in coaching methods as well as masters‐level degrees in social work or psychology. Coaches each had over 100 hours of experience of individualized coaching with type 2 diabetes patients and had previously facilitated diabetes coaching groups. Participants randomized to the coaching condition had an initial telephone session with their coach within 2 weeks of the baseline visit. They were then offered 30‐minute coaching sessions by telephone (8 weekly calls, 4 biweekly calls, and a final call 1 month later) for a total of 14 sessions. Participants were paired with the same coach throughout the intervention. During the initial telephone call, participants were asked what was important to them in terms of diabetes care, how well they were managing their health, and what they perceived to be their challenges or areas of required support. Patients were guided in creating a vision of health, and long‐term goals were discussed that aligned with that vision. To facilitate learning, participants randomized to IH coaching received a binder of educational materials at the initial assessment visit. Contents included materials from GlaxoSmithKline's Adherence Starts with Knowledge® (ASK‐20) and Essential Connections® as well as information from Duke Integrative Medicine. These were referenced throughout the interactions of the study. The ASK‐20 is a brief survey that helps practitioners quickly identify and target reasons patients may not be adhering to prescribed medication regimens. It is accompanied by materials on topics relevant to self management such as symptom recognition, self care, and disease risk factors. Duke Integrative Medicine provided information regarding nutrition, stress management, and tips on how to best utilize time with the coach. Additional materials came from Essential Connections, a resource of tools for coaches to facilitate motivational interviewing techniques and behavior change, linking topics of interest with patients' readiness to change and relevant education content | USUAL CARE: Control group participants received usual care, with no additional materials or correspondence | No for self reported adherence on the Morisky questionnaire | No for A1C at 6 months. No for stress at 6 months. No for quality of life between integrative health coaching and usual care patients at 6 months |
| Wu 2006 | Chronic illnesses receiving polypharmacy | INCREASED SUPERVISION BY PHARMACIST: Patients in the intervention group received 10‐ to 15‐minute telephone calls from the pharmacist at the midpoint between clinic visits, normally scheduled at intervals of 2 to 4 months, throughout the study period. During the telephone calls the pharmacist asked about the patient's current medication regime, clarified misconceptions, explained the nature of side effects, reminded patients of next appointment, reinforced importance of compliance with medications and relevant aspects of self care and encouraged patients to share side effects, self initiated change in regimen, or other concerns with the doctors at next follow‐up | USUAL CARE: Patients in the control group continued with usual care, which for clinically stable patients meant follow‐up at intervals of 2 to 4 months, with each consultation lasting 10 to 15 minutes | Yes for improving compliance to polypharmacy for chronic conditions | Yes for mortality, ER visits, and hospitalization |
| Wu 2012 | Chronic heart failure | LITE: The intervention was delivered by a cardiovascular nurse expert in delivery of the education and counseling intervention. Patients received the counseling intervention individually every other week for a total of 4 sessions. The first and third sessions were face‐to‐face education and counseling lasting 1 hour. The 2nd and 4th sessions were delivered by telephone and lasted 20 minutes each. The intervention was designed to influence medication adherence by creating a more positive attitude toward medication adherence, incorporating significant others into the patient education and counseling sessions to build a positive subjective norm, and providing needed information and skills to overcome barriers to adherence to increase the patient's perceived behavioral control | USUAL CARE: Received usual care. Participants completed a baseline survey, were contacted monthly to collect outcome, and completed a 9‐month questionnaire. In addition their MEMS data were downloaded at 1, 2, and 9 months | Yes for improving adherence to heart failure medication at 9 months in PLUS and LITE groups compared to control. Yes for improving adherence at 2 months in PLUS compared to control. No for improving adherence at 9 months in PLUS compared to LITE | Yes for improving cardiac event‐free survival in both interventions compared to controls at 9 months. No for improved quality of life over the 9‐month period |
| Wysocki 2001 | Diabetes | Behavioral‐Family Systems Therapy (BFST) ‐10 sessions consisting of 4 therapy components: problem‐solving training, communication skills training, cognitive restructuring and functional and structural family therapy, plus USD 100 monetary incentive for attending all 10 intervention sessions Education and Support (ES) ‐ families attended 10 group diabetes education and social support meetings (45‐minute educational presentation by diabetes professional + 45‐minute interaction among the families), plus USD 100 monetary incentive for attending all 10 intervention sessions (n = 40) | Current therapy ‐ standard pediatric endocrinology follow‐up and self management training | No for BFST and ES at post‐treatment. Yes for BFST at 6 and 12 months. No for ES at 6 and 12 months | No for BFST in diabetic control or adjustment to diabetes. Yes for BFST on PARQ scales at post‐treatment, 6, and 12 months. No for ES |
| Xiong 1994 | Schizophrenia | Family counseling and close follow‐up (n = 34) | Prescription of medication without formal follow‐up (n = 29) | No | Yes |
| Yopp 2004 | Adolescents with type 1 diabetes | Usual care (see Control) plus Multisystemic Therapy (MST; n = 27) ‐ a home‐based psychotherapy, the goal of which is to understand which factors are maintaining poor health status | Usual care in a multidisciplinary children's endocrinology clinic | No for the Diabetes Management Scale. Yes for the 24‐Hour Recall Interview, specifically the insulin adherence | No |
| Zhang 1994 | Schizophrenia | Family intervention (n = 42) | Prescription of medication without formal follow‐up (n = 41) | No | Yes |
| Zolfaghari 2012 | Type 2 diabetes | SHORT MESSAGE SYSTEM (SMS) GROUP: Participants in both groups received 3 days of diabetes self care education sessions. Before the intervention, the SMS group received 10 minutes of instruction on how to use their cell phones and check their ability to read the SMS. The intervention was provided for 3 months. Patients in the SMS group received about 6 messages every week (excluding holidays) that consisted information about taking a diet, exercising, diabetic medication taking, frequent self monitoring of blood glucose levels, and stress management. Overall, 72 messages were sent to patients during intervention, and the length of each message was not more than 160 features. Participants in the SMS group could receive messages at any place where access was possible by cellular phone. The researcher sent optimal recommendations back to each patient, 6 times by SMS of a cellular phone weekly | TELEPHONE INTERVENTION GROUP: The intervention for the Telephone Group was provided via telephone for 3 months. The intervention was provided by counseling scheduled appointments – whenever the time was convenient to the subject. The content of intervention consisted of counseling on the nature of the disease, risk factors, importance of maintaining blood glucose levels within a near‐normal range, continuous education and reinforcement of diet, exercise, medications taking, hypoglycemia management, illness management, how to record daily blood glucose and frequent self monitoring of blood glucose levels. The researcher contacted the telephone group at least twice a week for the first month and then weekly for the 2nd and 3rd month. The total frequency of telephone counseling averaged 16 times per subject. The average length of these contacts was 20 minutes per call. "The researcher asked questions about the diet: 'Did you eat salad and vegetable before every meal?', 'How many days did you follow your recommended diet over the past days?' 'Did you eat your meals at regular times?' and…some recommendations about exercising such as: 'How many times did you do physical exercising or walking during the last days?' 'When is the best time to exercise'? 'Did you feel better after exercising?' 'Do you know that exercising is as important as diabetic medication?' and medication‐related questions were: 'Did you take your recommended diabetic medication?' 'When did you consume your prescribed tablet? 'Do you know how your consuming medications, act in your body?'…and so on" | No for improving medication adherence in diabetic patients with an SMS intervention at 6 months | No for improving HbA1C levels at 6 months. No difference in HbA1c levels between the groups |
Comparison 1 Studies that met criteria, Outcome 1 Adherence and outcome.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Adherence and outcome Show forest plot | Other data | No numeric data | ||
