Electronic Adherence Monitoring Research Articles

Can Short-Term Use of Electronic Patient Adherence Monitoring Devices Improve Adherence in Patients Failing Second-Line Antiretroviral Therapy? Evidence from a Pilot Study in Johannesburg, South Africa.

High levels of adherence are required to achieve the full benefit of ART. We assess the effectiveness of electronic adherence monitoring devices among patients failing second-line ART, as measured by viral load suppression. Cohort study of Wisepill™ real-time adherence monitoring in addition to intensified adherence counselling over 3 months in adults with a viral load ≥400 copies/ml on second-line ART in Johannesburg, South Africa between August 2013 and January 2014. Patients were sent SMS reminders upon missing a scheduled dose. We compared outcomes to earlier historical cohorts receiving either intensified adherence counselling or adherence counselling alone. Overall, 63 % of the participants (31/49) took >80 % of their prescribed medication; this dropped from 76 to 53 and 49 % at 1, 2 and 3 months post-enrolment respectively. Compared to those with good adherence (>80 %), participants with poor adherence (≤80 %) had a higher risk for a subsequently elevated viral load ≥400 copies/ml (relative risk (RR) 1.47 95 % CI 0.97–2.23). Participants found the intervention “acceptable and useful” but by 6 months after eligibility they were only slightly more likely to be alive, in care and virally suppressed compared to those who received intensified adherence counselling (44.9 vs. 38.5 %; RR 1.19; 95 % CI 0.85–1.67) or adherence counselling alone (44.9 vs. 40.9 %; RR 1.12; 95 % CI 0.81–1.56). In patients with an elevated viral load on second-line ART electronic adherence monitoring was associated with a modest, but not significant, improvement in viral suppression.

Association of disclosure of HIV status with medication adherence

ObjectiveDisclosure may affect adherence to antiretroviral treatment. In a medication adherence program, this cross-sectional study describes disclosure, perceived reaction after disclosure, living situations, and the relationship of disclosure with antiretroviral adherence. MethodsA combination of a questionnaire to measure disclosure and longitudinal electronic monitoring of medication adherence was used. ResultsA total of 103 out of 159 eligible patients gave informed consent. The characteristics differed between participants and nonparticipants (race, education, sexual orientation, medication adherence). Thirteen participants did not disclose their HIV status. Seventy-three (81%) participants judged the reaction after disclosure positive. Among the 62 participants cohabiting, 52% disclosed to all co-residents. Adherence was high (median 100%). HIV disclosure was negatively associated with adherence, when disclosing to the mother (OR=2.46, p-value=0.086) and to siblings (OR=2.89, p-value=0.029). Living alone was associated to a lower adherence than cohabitation (Rate Ratio=1.42, p-value=0.007). ConclusionHIV disclosure and adherence are sensitive issues, which may explain the reason for refusal. Nonparticipants may be those with the most difficulties disclosing. Practice implicationsAn unbiased collection of sensitive information, as HIV disclosure, is a difficult task. A cohort design, with research data collected systematically by a trusted healthcare provider, may better describe the association between adherence and disclosure.

Pharmacists' perspectives on monitoring adherence to treatment in Cystic Fibrosis.

Cystic Fibrosis (CF) management requires complex treatment regimens but adherence to treatment is poor and has negative health implications. There are various methods of measuring adherence, but little is known regarding the extent of adherence measurement in CF centres throughout the UK and Ireland. To determine the adherence monitoring practices in CF centres throughout the UK and Ireland, and to establish CF pharmacists' views on these practices. UK and Ireland Cystic Fibrosis Pharmacists' Group's annual meeting (2014). A questionnaire was designed, piloted and distributed to pharmacists attending the UK and Ireland Cystic Fibrosis Pharmacists' Group's annual meeting (2014). The main outcome measures were the methods of inhaled/nebulised antibiotic supply and the methods used to measure treatment adherence in CF centres. The questionnaire also ascertained the demographic information of participating pharmacists. Closed question responses were analysed using descriptive statistics. Open questions were analysed using content analysis. Twenty-one respondents (84 % response) were included in the analysis and were mostly from English centres (66.7 %). Detailed records of patients receiving their inhaled/nebulised antibiotics were lacking. Adherence was most commonly described to be measured at 'every clinic visit' (28.6 %) and 'occasionally' (28.6 %). Patient self-reported adherence was the most commonly used method of measuring adherence in practice (90.5 %). The availability of electronic adherence monitoring in CF centres did not guarantee its use. Pharmacists attributed an equal professional responsibility for adherence monitoring in CF to Consultants, Nurses and Pharmacists. Seventy-six percent of pharmacists felt that the current adherence monitoring practices within their own unit were inadequate and associated with the absence of sufficient specialist CF pharmacist involvement. Many suggested that greater specialist pharmacist involvement could facilitate improved adherence monitoring. Current adherence knowledge is largely based on self-report. Further work is required to establish the most appropriate method of adherence monitoring in CF centres, to improve the recording of adherence and to understand the impact of increased specialist pharmacist involvement on that adherence.

A Randomized Controlled Trial of Real-Time Electronic Adherence Monitoring With Text Message Dosing Reminders in People Starting First-Line Antiretroviral Therapy.

There are conflicting findings about whether mobile phone text message reminders impact on antiretroviral adherence. We hypothesized that text reminders sent when dosing was late would improve adherence and HIV viral suppression. Antiretroviral therapy (ART)-naive participants, from a South African outpatient ART clinic, were randomized to standard of care (SoC, 3 pretreatment education sessions), or intervention (SoC and automated text reminders if dosing >30 minutes late). Dosing time was recorded by real-time electronic adherence monitoring devices, given to participants at ART start. CD4 cell count and HIV RNA were determined at baseline, 16 and 48 weeks. Primary outcome was cumulative adherence execution by electronic adherence monitoring device. HIV-1 viral suppression (<40 copies/mL) at week 48 and count of treatment interruptions (TIs) >72 hours were secondary outcomes. Analysis was by intention to treat (missing = failure). Registration was with the Pan-African Clinical Trials Registry: PACTR201311000641402. A total of 230 participants were randomly assigned to control (n = 115) or intervention (n = 115) arms. Median adherence was 82.1% (interquartile range, 56.6%-94.6%) in the intervention arm, compared with 80.4% (interquartile range, 52.8%-93.8%) for SoC [adjusted odds ratio for adherence 1.08; 95% confidence interval (CI): 0.77 to 1.52]. Suppressed HIV RNA (<40 copies/mL) occurred in 80 (69.6%) of control and 75 (65.2%) of intervention (adjusted odds ratio for virological failure in intervention arm 0.77; 95% CI: 0.42 to 1.40). In the intervention arm, the count of TIs of >72 hours was reduced (adjusted incident rate ratio, 0.84; 95% CI: 0.75 to 0.94). Text message reminders linked to late doses detected by real-time adherence monitoring reduced the number of prolonged TIs, but did not significantly improve adherence or viral suppression.

The Effect of Adherence-Encouraging Interventions on Adherence to Tyrosine Kinase Inhibitor Treatment in Chronic Myeloid Leukemia (TAKE-IT): A Pre-Post Intervention Pilot Study

Introduction: Medication non-adherence (MNA) to tyrosine kinase inhibitors TKIs occurs in around 30% of chronic myeloid leukemia (CML) patients and is associated with adverse outcomes (Noens, 2009; Marin, 2010). Data on adherence-enhancing interventions (AEIs) in CML are scarce and an improvement in dose implementation has yet to be shown.Objective: To evaluate the efficacy of a multilevel AEI in improving MNA to TKIs in CML.Methods: We initiated a prospective multicenter (N=4) pre-post adherence intervention pilot study in CML (NCT01768689). Patients were eligible if they had received at least 3 months of imatinib, nilotinib or dasatinib for CML, irrespective of treatment line or subsequent duration. TKI adherence was assessed for 7.5 months using electronic monitoring (EM) with MEMS (Medical Events Monitoring System 6) and BAASIS. The MEMS bottle cap contains a micro-electronic circuit that registers dates and times of cap opening. The BAASIS is a 4-item patient reported outcome used to assess adherence in solid organ transplants and CML (Cleemput, 2007; Noens, 2009).We designed an investigational AEI to address known barriers to TKI adherence in CML (Figures 1 & 2), using components with proven efficacy in improving MNA in chronic diseases. The key elements were: behavioral change techniques (BCT); motivational interviewing (MI; Figure 2); and multilevel including patient (Figure 1), peer group and health care provider levels (not shown). The BCT taxonomy developed by Michie et al (Ann Behav Med, 2013) was used in Figures 1 & 2 to describe the intervention and to facilitate its reproducibility.During the first 4.5 months of adherence monitoring, MNA was managed as per local practice. The intervention phase was then initiated (Figure 1) and adherence measured for a further 3 months. The pre and post-intervention periods were defined as the 3 months before and after the initiation of the AEI, respectively. The primary outcome measure was EM adherence using MEMS, and primary analysis was the comparison between pre and post-intervention adherence, expressed as the percentage of days with drug taken as prescribed. Generalized Estimating Equation model was used to adjust for correlation between adherence levels pre and post intervention, measured in the same patient. We also explored the association between adherence according to BAASIS (at 3 different time-points during the pre/post intervention periods) and the corresponding 1-month periods of EM adherence.Results: Between 10/2013 and 7/2014, we enrolled 55 CML patients (median age, 60.5 years; median current TKI duration, 34 months) receiving imatinib (59%), nilotinib (18%) or dasatinib (23%).Median pre-intervention EM adherence was 97.5% (min 48%; 10th percentile: 82.6%; 25th: 92.1%; 75th: 99.3%; 90th: 100%; max 100%) and the mean was 93%. Non-membership in a CML patients group (51%), living alone (18%) and 3rd line treatment (9%) were each risk factors for pre-intervention MNA on multivariate analysis, whereby mean adherence was 7% (p<0.01), 10.2% (p=0.03) and 13.9% (p=0.01) lower than patients without each of these risk factors, respectively. The estimated mean adherence was near perfect (99.7%) with none of the above risk factors (N=21; 38%).The AEI affected a 1.45% improvement in adherence for the whole cohort (95% CI: 0.09-2.8%, p=0.04). The AEI led to an improvement of 2.51% in the non-members of a CML patient group (95% CI: 0.2-4.8%, p=0.03) relative to 0.25% (p=0.71) in the members. By extrapolation, this corresponds to an additional 5.3 days of correct intakes over 1 year for the whole cohort, and 9.5 days for non-members of a CML patient group. Using an exploratory cut-off of EM adherence ≥ 95% as adherent, the BAASIS (N=132) correctly classified 75.5% (74/98) as adherent and 73% (25/34) as non-adherent.Conclusion: The effect of the AEI is modest but statistically significant, and higher in non-members of a CML patients group. At the same time, this study shows the futility and potential resource wasting of trying to improve adherence in the large group of near-perfect adherers without risk factors. Our pilot study provides proof of concept that EM adherence may be improved in CML patients by a multilevel AEI, and that the magnitude of improvement is higher in subgroups at risk. These subgroups should be identified, if possible, by combining patient characteristics with the BAASIS. [Display omitted] [Display omitted] DisclosuresLeader:Novartis: Research Funding. Sharf:Pfizer: Honoraria; BMS: Honoraria, Research Funding; Gilead: Honoraria; Novartis: Honoraria, Research Funding; Ariad: Honoraria, Research Funding. Tousset:MWV Healthcare: Employment. Ellis:Novartis: Other: Advisory Board; Pfizer: Other: Advisory Board. Raanani:BMS: Other: Advisory Board; Pfizer: Other: Advisory Board; Novartis: Other: Advisory Board, Research Funding; Ariad: Other: Advisory Board.

Trials and tribulations with electronic medication adherence monitoring in kidney transplantation.

Medication adherence in kidney transplantation is critical to prevent graft rejection. Testing interventions designed to support patients to take their prescribed medications following a kidney transplant require an accurate measure of medication adherence. In research, the available methods for measuring medication adherence include self-report, pill counts, prescription refill records, surrogate measures of medication adherence and medication bottles with a microchip-embedded cap to record bottle openings. Medication bottles with a microchip-embedded cap are currently regarded as the gold standard measure. This commentary outlines the challenges in measuring medication adherence using electronic medication monitoring of kidney transplant patients recruited from five sites. The challenges included obtaining unanimous stakeholder support for using this method, agreement on an index medication to measure, adequate preparation of the patient and training of pharmacy staff, and how to analyze data when periods of time were not recorded using the electronic adherence measure. Provision of this information will enable hospital and community pharmacists to implement approaches that promote the effective use of this adherence measure for optimal patient outcomes.

Can You Teach a Teen New Tricks? Problem Solving Skills Training Improves Oral Medication Adherence in Pediatric Patients with Inflammatory Bowel Disease Participating in a Randomized Trial.

Medication nonadherence is associated with higher disease activity, greater health care utilization, and lower health-related quality of life in pediatric inflammatory bowel diseases (IBD). Problem solving skills training (PSST) is a useful tool to improve adherence in patients with chronic diseases but has not been fully investigated in IBD. This study assessed feasibility, acceptability, and preliminary efficacy of PSST in pediatric IBD. Recruitment occurred during outpatient clinic appointments. After completion of baseline questionnaires, families were randomized to a treatment group or wait-list comparison group. The treatment group received either 2 or 4 PSST sessions. Youth health-related quality of life was assessed at 3 time points, and electronic monitoring of oral medication adherence occurred for the study duration. Seventy-six youth (ages 11-18 years) on an oral IBD maintenance medication participated. High retention (86%) and treatment fidelity rates (95%) supported feasibility. High satisfaction ratings (mean values ≥4.2 on 1-5 scale) supported intervention acceptability. Modest increases in adherence occurred after 2 PSST sessions among those with imperfect baseline adherence (d = 0.41, P < 0.10). Significant increases in adherence after 2 PSST sessions were documented for participants aged 16 to 18 years (d = 0.95, P < 0.05). Improvements in health-related quality of life occurred after 2 PSST sessions. No added benefit of 4 sessions on adherence was documented (d = 0.05, P > 0.05). Phone-delivered PSST was feasible and acceptable. Efficacy estimates were similar to those of lengthier interventions conducted in other chronic illness populations. Older adolescents benefited more from the intervention than their younger counterparts.

Ethical Questions in Medical Electronic Adherence Monitoring.

Electronic adherence monitors (EAMs) record and report an array of health behaviors, ranging from taking daily medications to wearing medical devices. EAMs are utilized in research worldwide and are being investigated for clinical use. However, there is also growing popular concern about the extent to which electronic devices may be used to monitor individuals, including allegations in the media that EAMs represent a move towards "Big Brother" in medicine. Here, we highlight the unique benefits as well as the potential ethical challenges that electronic adherence monitoring generates. These challenges surround autonomy, privacy and confidentiality, trust, and ancillary care obligations. We describe key questions within each of these domains that warrant further investigation, and present potential solutions to many of the concerns raised.

Defining success with HIV pre-exposure prophylaxis: a prevention-effective adherence paradigm.

Clinical trial data have shown that oral pre-exposure prophylaxis (PrEP) is efficacious when taken as prescribed; however, PrEP adherence is complex and must be understood within the context of variable risk for HIV infection and use of other HIV prevention methods. Different levels of adherence may be needed in different populations to achieve HIV prevention, and the optimal methods for achieving the necessary adherence for both individual and public health benefits are unknown. Guidance for PrEP use must consider these questions to determine the success of PrEP-based HIV prevention programs. In this article, we propose a new paradigm for understanding and measuring PrEP adherence, termed prevention-effective adherence, which incorporates dynamic HIV acquisition risk behaviors and the use of HIV alternative prevention strategies. We discuss the need for daily PrEP use only during periods of risk for HIV exposure, describe key issues for measuring and understanding relevant behaviors, review lessons from another health prevention field (i.e., family planning), and provide guidance for prevention-effective PrEP use. Moreover, we challenge emerging calls for sustained, near perfect PrEP adherence regardless of risk exposure and offer a more practical and public health-focused vision for this prevention intervention.

Electronic monitoring reveals highly variable adherence patterns in patients prescribed ivacaftor

BackgroundPrevious studies of CF treatments have shown suboptimal adherence, though little has been reported regarding adherence patterns to ivacaftor. Electronic monitoring (EM) of adherence is considered a gold standard of measurement. MethodsAdherence rates by EM were prospectively obtained and patterns over time were analyzed. EM-derived adherence rates were compared to pharmacy refill history and self-report. Results12 subjects (age 6–48years; CFTR-G551D mutation) previously prescribed ivacaftor were monitored for a mean of 118days. Overall adherence by EM was 61%(SD=28%) and decreased over time. Median duration between doses was 16.9hours (IQR 13.9–24.1hours) and increased over time. There was no correlation between EM-derived adherence and either refill history (84%, r=0.26, p=0.42) or self-report (100%, r=0.40, p=0.22). ConclusionsDespite the promising nature of ivacaftor, our data suggest adherence rates are suboptimal and comparable to other prescribed CF therapies, and more commonly used assessments of adherence may be unreliable.

Post awakening salivary cortisol secretion and trait well-being: The importance of sample timing accuracy

Indices of post awakening cortisol secretion (PACS), include the rise in cortisol (cortisol awakening response: CAR) and overall cortisol concentrations (e.g., area under the curve with reference to ground: AUCg) in the first 30-45 min. Both are commonly investigated in relation to psychosocial variables. Although sampling within the domestic setting is ecologically valid, participant non-adherence to the required timing protocol results in erroneous measurement of PACS and this may explain discrepancies in the literature linking these measures to trait well-being (TWB). We have previously shown that delays of little over 5 min (between awakening and the start of sampling) to result in erroneous CAR estimates. In this study, we report for the first time on the negative impact of sample timing inaccuracy (verified by electronic-monitoring) on the efficacy to detect significant relationships between PACS and TWB when measured in the domestic setting. Healthy females (N=49, 20.5±2.8 years) selected for differences in TWB collected saliva samples (S1-4) on 4 days at 0, 15, 30, 45 min post awakening, to determine PACS. Adherence to the sampling protocol was objectively monitored using a combination of electronic estimates of awakening (actigraphy) and sampling times (track caps). Relationships between PACS and TWB were found to depend on sample timing accuracy. Lower TWB was associated with higher post awakening cortisol AUCg in proportion to the mean sample timing accuracy (p<.005). There was no association between TWB and the CAR even taking into account sample timing accuracy. These results highlight the importance of careful electronic monitoring of participant adherence for measurement of PACS in the domestic setting. Mean sample timing inaccuracy, mainly associated with delays of >5 min between awakening and collection of sample 1 (median=8 min delay), negatively impacts on the sensitivity of analysis to detect associations between PACS and TWB.

Abstract 343: Electronically-measured, but Not Self-reported, Medication Adherence is Associated with Healthcare Utilization in Patients with Uncontrolled Hypertension

Introduction: Non-adherence to antihypertensive medications can lead to poorly controlled hypertension and increased cardiovascular risk. Prior studies utilizing pharmacy refill data have shown an association between medication non-adherence and increased healthcare utilization. However, data are lacking as to whether electronically measured, day-to-day adherence is associated with healthcare utilization. Methods: Between 2011 and 2014, we enrolled a convenience sample of 161 patients with treated but uncontrolled hypertension from a primary care clinic. Adherence to up to 4 blood pressure (BP) medications was electronically measured during the interval between two clinic visits using a 4-compartment electronic pillbox (MedSignals) that records the date and time each compartment is opened. Adherence to each medication was calculated as the percent of days the correct number of doses of a particular medication was taken as prescribed; regimen adherence was the mean adherence to monitored medications. Adherence was also measured after completion of the electronic monitoring period using the 8-item Morisky Medication Adherence Scale. Healthcare utilization (cardiac procedures, including EKGs, stress tests and echocardiograms; ED visits; all-cause hospitalizations; scheduled primary care visits) was assessed via review of the electronic medical record in the 1 year after electronic monitoring. Logistic regression and negative binomial regression analyses were used to model the association between electronic adherence and healthcare utilization adjusting for covariates (age, gender, ethnicity, race, Charlson Comorbidity Index, Medicaid status, BP, PTSD, depression). Results: The mean age was 65 years, 75% were female, 80% Hispanic, 86% had Medicaid, and 52% were non-adherent by electronic monitoring. Non-adherent patients were more likely to have ≥1 cardiac procedures (27% vs. 10%, p=0.004), ED visits (35% vs. 13%, p=0.001), and hospitalizations (27% vs. 12%, p=0.01) compared to adherent patients, but did not have more primary care visits (p=0.55). In adjusted analyses, non-adherent patients had more ED visits (adjusted rate ratio [aRR] 2.4 [95% CI 1.3-4.6], p&lt;0.01), primary care visits (aRR 1.2 [95% CI 1.01[[Unable to Display Character: &amp;#8211;]]1.4], p=0.04), and cardiac procedures (aRR 4.5 [95% CI 1.8-11.4], p=0.001) compared to adherent patients, and were more likely to have ≥1 hospitalizations (adjusted OR 2.9 [95% CI 1.1-7.5], p=0.02). Self-reported adherence was not associated with any of the healthcare utilization measures (p&gt;0.40 for all measures). Discussion: We found associations between electronically-measured, but not self-reported, medication adherence and healthcare utilization. These findings suggest that electronic adherence monitoring may be a useful tool for identifying high utilizers of healthcare resources and targeting such patients for cost-reduction strategies.

Antiretroviral Non-Adherence is Associated With a Retrieval Profile of Deficits in Verbal Episodic Memory

HIV-associated deficits in verbal episodic memory are commonly associated with antiretroviral non-adherence; however, the specific aspects of memory functioning (e.g., encoding, consolidation, or retrieval) that underlie this established relationship are not well understood. This study evaluated verbal memory profiles of 202 HIV+ participants who underwent a 30-day electronic monitoring of antiretroviral adherence. At the group level, non-adherence was significantly associated with lower scores on immediate and delayed passage recall and word list learning. Retention and recognition of passages and word lists were not related to adherence. Participants were then classified as having either a normal verbal memory profile, a “subcortical” retrieval profile (i.e., impaired free recall with relatively spared recognition), or a “cortical” encoding profile (e.g., cued recall intrusions) based on the Massman et al. (1990) algorithm for the California Verbal Learning Test. HIV+ participants with a classic retrieval deficit had significantly greater odds of being non-adherent than participants with a normal or encoding profile. These findings suggest that adherence to prescribed antiretroviral regimens may be particularly vulnerable to disruption in HIV+ individuals due to deficits in the complex process of efficiently accessing verbal episodic information with minimal cues. A stronger relationship between non-adherence and passage (vs. word list) recall was also found and may reflect the importance of contextual features in remembering to take medications. Targeted interventions for enhancing and supporting episodic memory retrieval processes may improve antiretroviral adherence and overall health outcomes among persons living with HIV.

Low-Magnitude Mechanical Stimulation to Improve Bone Density in Persons of Advanced Age: A Randomized, Placebo-Controlled Trial.

Nonpharmacologic approaches to preserve or increase bone mineral density (BMD) include whole-body vibration (WBV), but its efficacy in elderly persons is not clear. Therefore, we conducted the Vibration to Improve Bone in Elderly Subjects (VIBES) trial, a randomized, placebo-controlled trial of 10 minutes of daily WBV (0.3g at 37 Hz) in seniors recruited from 16 independent living communities. The primary outcomes were volumetric BMD of the hip and spine measured by quantitative computed tomography (QCT) and biochemical markers of bone turnover. We randomized 174 men and women (89 active, 85 placebo) with T-scores -1 to -2.5 who were not taking bone active drugs and had no diseases affecting the skeleton (mean age 82 ± 7 years, range 65 to 102). Participants received daily calcium (1000 mg) and vitamin D (800 IU). Study platforms were activated using radio frequency ID cards providing electronic adherence monitoring; placebo platforms resembled the active platforms. In total, 61% of participants in the active arm and 73% in the placebo arm completed 24 months. The primary outcomes, median percent changes (interquartile range [IQR]) in total volumetric femoral trabecular BMD (active group (2.2% [-0.8%, 5.2%]) versus placebo 0.4% [-4.8%, 5.0%]) and in mid-vertebral trabecular BMD of L1 and L2 (active group (5.3% [-6.9%, 13.3%]) versus placebo (2.4% [-4.4%, 11.1%]), did not differ between groups (all p values > 0.1). Changes in biochemical markers of bone turnover (P1NP and sCTX) also were not different between groups (p = 0.19 and p = 0.97, respectively). In conclusion, this placebo-controlled randomized trial of daily WBV in older adults did not demonstrate evidence of significant beneficial effects on volumetric BMD or bone biomarkers; however, the high variability in vBMD changes limited our power to detect small treatment effects. The beneficial effects of WBV observed in previous studies of younger women may not occur to the same extent in elderly individuals.

Emerging technologies for electronic monitoring of adherence, inhaler competence, and true adherence.

Despite the availability of effective treatments for respiratory disorders, disease control is often suboptimal, due in part to the failure of patients to adhere to prescribed regimens, or to demonstrate competence with the often complex steps in the administration of inhaled medications. The cost of poor true adherence, a combined measure of adherence and inhaler competence, is considerable, both economically and in terms of health-related impact. While patient education is recognized as essential, there exist many barriers to healthcare professional-led monitoring and promotion of true adherence. Successful intervention remains a challenging task, dependent upon understanding and addressing the distinct issues associated with poor adherence and inhaler competence, and lessening the perceived burden on healthcare professionals. Electronic monitors provide an accurate and objective indication of adherence and may also be of value in assessing inhaler competence. The information provided by such devices is a helpful aid to understanding the challenging nature of true adherence, and may be crucial to the development and assessment of true adherence promoting interventions. This article provides a background to the impact of suboptimal adherence and inhaler competence, and the challenges associated with the promotion of true adherence, with an emphasis on respiratory therapies. Contemporary electronic monitors of adherence and inhaler competence are critically reviewed, and case studies of emerging technologies are provided to illustrate the use of innovative monitoring devices in the promotion of true adherence in practice. Potential future directions, including increased targeting and individualization, enhanced coordination of care, and a greater focus on inhaler competence are considered to be important additions to currently available technologies in this rapidly evolving field.

Electronic Monitoring of Adherence to Inhaled Medication in Asthma

The main treatment of asthma is inhaled corticosteroids. However adherence to these medications in asthma is often poor, with low adherence associated with excessive health care costs and an increased risk of emergency room visits and mortality. Although various methods are used to indirectly assess adherence, all have significant limitations whether used in clinical or research practice. The recent development of electronic monitoring devices (EMDs) for use with inhalers presents an exciting opportunity to easily and accurately measure inhaler adherence. This article summarises the current devices available; for each device features and limitations are considered, followed by a review of both the current clinical literature and data on reliability and accuracy. An overall summary is also provided to aid comparison of capabilities between devices and future issues pertaining to the use of EMDs are discussed, including barriers to adoption, stakeholder involvement, novel methods of communicating adherence data, recording of data and cloud storage. Finally key areas that still require investigation are highlighted.

Electronic monitoring to assess adherence with once-daily glaucoma medications and risk factors for nonadherence: the automated dosing reminder study.

Adherence with topical glaucoma medications is low in some patients. To identify these patients, we need more information on risk factors for nonadherence. To assess adherence with once-daily glaucoma medication. Prospective cohort study involving patients who were recruited from a university-based glaucoma clinic and treated with once-daily prostaglandin eyedrops. Baseline characteristics were recorded, and each patient was provided a medication bottle to hold his or her eyedrop bottle throughout the study. An electronic cap recorded each time the larger bottle holding the eyedrops was opened. Participants were administered standardized tests of depression and mental status and answered questions about their health and their attitudes toward medication adherence. They used the electronic monitors for 3 months, during which their adherence with medications was assessed. Adherence with daily glaucoma medication and factors associated with poor adherence. Of the 491 participants enrolled, 407 (82.9%) successfully completed the 3-month adherence assessment. Of this group, 337 (82.8%) took their medication correctly on at least 75% of days and were deemed adherent. Compared with this adherent group, the 70 participants (17.2%) who were nonadherent were slightly younger, were more likely to be of African descent, took medications for a shorter time, had a lower level of educational attainment, and had worse scores on mental status and depression scales (P < .05 for all). Nonadherent participants were less likely to be able to name their glaucoma medications, reported a lower estimate of adherence, and were more likely to admit some missed doses over the past 2 weeks or in general (P < .05 for all). Those who were nonadherent were also less likely to agree that remembering their eyedrops is easy, more likely to strongly agree with the statement that eyedrops can cause problems, and less likely to agree that they followed physicians' orders. Electronic monitoring of patient adherence documented that a sizable number of patients with glaucoma do not take their medications as prescribed. Factors were identified that may prove useful in targeting those nonadherent patients for interventions.

Adherence in childhood asthma: the elephant in the room.

Adherence to inhaled steroids is suboptimal in many children with asthma and can lead to poor disease control. Many previous studies in paediatric populations have used subjective and inaccurate adherence measurements, reducing their validity. Adherence studies now often use objective electronic monitoring, which can give us an accurate indication of the extent of non-adherence in children with asthma. A review of the studies using electronic adherence monitoring shows that half of them report mean adherence rates of 50% or below, and the majority report rates below 75%. Reasons for non-adherence are both intentional and non-intentional, incorporating illness perceptions, medication beliefs and practical adherence barriers. Interventions to improve adherence in the paediatric population have had limited success, with the most effective containing both educational and behavioural aspects.

The critical importance of medication adherence and its assessment: a comment on Sutton et Al.

The importance of adherence, a term used to describe “the extent to which an individual’s behavior coincides with healthrelated instructions or recommendations given by a health-care provider in the context of a specific disease or disorder” [1], cannot be overstated in the context of both behavioral and biopharmaceutical interventions for chronic diseases such as hypertension and diabetes, which have reached epidemic proportions worldwide [2, 3]. It is therefore pleasing to see the paper by Sutton et al., printed in this issue, which reports the results of a randomized controlled trial focusing on electronic monitoring and measurement reactivity [4]. In multiple facets of science, the act of measurement itself is capable of altering the characteristic(s) of the parameter that we wish to measure. In the context of adherence assessment, it is therefore important to know whether the measurement tool itself elicits a change in adherence behavior, and if so of what magnitude. The rigorous evaluation and report by Sutton et al. suggests that electronic monitoring of adherence to a biopharmaceutical regimen for type 2 diabetes may itself lead to a small, statistically nonsignificant change in adherence. This is an important result, but, as the authors observe, one that should be weighed in the overall context of the critical importance of adherence assessment and the “gold standard” status afforded to electronic monitoring. Information is power, and this study has added useful information to contemporary and subsequent discussions of a powerful measurement methodology. The discipline of behavioral medicine has provided evidence that “behavioral interventions aimed at modifying lifestyle or psychosocial variables can help prevent morbidity and/or mortality in high-risk populations” [5]: this includes observations that lifestyle interventions targeting increased physical activity and weight loss can reduce the incidence of diabetes in prediabetic individuals [6, 7]. However, when the potential therapeutic benefits of behavioral interventions are not fully realized for an individual, biopharmaceutical interventions are the next step. As the European Medicines Agency has observed, “Glucose control in type 2 diabetes deteriorates progressively over time, and, after failure of diet and exercise alone, needs on average a new [biopharmaceutical] interventionwith glucose-lowering agents every 3–4 years in order to obtain/retain good control” [8]. For such pharmacotherapy to yield therapeutic benefit, individuals must be appropriately adherent. Medication adherence is also of critical importance for another chronic disease for which the first-line interventions are behavioral, i.e., hypertension. When discussing the results presented by Lim et al. [2], Dolan and O’Brien observed that “ischaemic heart disease, ischaemic, nonischaemic, and haemorrhagic stroke, hypertensive disease, atrial fibrillation and flutter, peripheral vascular disease, aortic aneurysm, and chronic renal disease (to which we must now add cognitive impairment and dementia) are all attributed to hypertension” [9]. These authors also noted the paradox of continued rampant hypertension despite our possessing many pharmacological agents that, if used appropriately, provide therapeutic benefit. Lack of patient adherence to appropriately prescribed regimens is one major problem in this field [10]. Sutton et al. [4] acknowledge that further investigations are needed in this field: I hope that behavioral scientists will J. R. Turner (*) Clinical Communications, Quintiles, Durham, NC, USA e-mail: rick.turner@quintiles.com

Electronic Monitoring of Medication Adherence in a 1-year Clinical Study of 2 Dosing Regimens of Mesalazine for Adults in Remission with Ulcerative Colitis

Adherence to medication is an issue of great importance for patients with ulcerative colitis. Once daily mesalazine seems to be no worse than divided doses in preventing relapse in remitting patients. Although this has been attributed to improved adherence, detailed measures of adherence have been lacking from previous studies. A 1-year substudy was conducted alongside a trial that compared 2 different dosing regimens (once daily versus three times daily) of mesalazine for patients in remission with ulcerative colitis. Participants in the substudy had their adherence monitored electronically using the medication event monitoring system, self-report, and tablet counts. We compared measures, determined factors associated with adherence and associations between adherence and relapse, modeled adherence over time, and explored behavioral aspects. We included 58 participants. Adherence was high across all measures (89.3% self-report, 96.7% tablet counts, and 89.2% medication event monitoring system). Agreement between the measures was poor at times. Adherence according to the medication event monitoring system best distinguished between the participants who relapsed (71.4%) and those who remained in remission (93.4%), although this difference was not statistically discernible at the 5% level. Adherence deteriorated over the study period, with three times daily participants generally less adherent than once-daily participants (odds ratio, 0.03; 95% confidence interval, 0.01-0.08). Adherence was higher on weekdays (odds ratio, 1.47; 95% confidence interval, 1.31-1.65) and around clinic visit dates (odds ratio, 1.43; 95% confidence interval, 1.18-1.72). Simple dosing regimens are preferable to multiple daily dosing regimens. Electronic monitoring of adherence should be used more often in clinical studies. Self-reported adherence and tablet counts may underestimate adherence. Adherence declined over time, and adherence was generally lower and more varied for those allocated to the three times daily regimen.