A Method to Calculate Adherence to Inhaled Therapy That Reflects the Changes in Clinical Features of Asthma.

Rationale Currently studies on adherence to inhaled medications report Average Adherence over time. This measure does not account for variations in the interval between doses nor for errors in inhaler use. Objectives We investigated whether adherence calculated as a single Area Under the concentration-time Curve (AUC) measure, incorporating the interval between doses and inhaler technique, was more reflective of patient outcomes than current methods of assessing adherence. Methods We attached a digital audio device (INCATM) to a dry powder inhaler. This recorded when the inhaler was used and analysis of the audio data indicated if the inhaler had been used correctly. These aspects of inhaler use were combined to calculate adherence over time, as an AUC measure. Over a 3 month period a cohort of asthma patients were studied. Adherence to a twice-daily inhaler preventer therapy using this device and clinical measures were assessed. Measurements and Results Recordings from 239 patients with severe asthma were analysed. Average Adherence, based on the dose counter was 84.4%, whereas the ratio of expected to observed accumulated AUC, Actual Adherence, was 61.8% (

Objective Assessment of Adherence to Inhalers by COPD Patients.

RATIONALE: Objective adherence to inhaled therapy by patients with COPD has not been reported. OBJECTIVES: The aim of this study was to objectively quantify adherence to preventer DiskusTM inhaler therapy by patients with COPD with an electronic audio recording device (INCATM). METHODS: This was a prospective observational study. On discharge from hospital patients were given a salmeterol/fluticasone inhaler with an INCATM device attached. Analysis of this audio quantified the frequency and proficiency of inhaler use. MEASUREMENTS AND MAIN RESULTS: COPD patients (n=265) were recruited. The mean age 71 years, mean Forced Expiratory Volume in 1-second 1.3 Litres, and 80% had evidence of mild/moderate cognitive impairment. By combining time of use, interval between doses and critical technique errors, thus incorporating both intentional and unintentional non-adherence, a measure \u22Actual Adherence\u22 was calculated. Mean Actual Adherence was 22.9% of that expected if the doses were taken correctly and on time. Seven percent had an Actual Adherence\u3e80%. Hierarchical clustering found three equally sized well-separated clusters corresponding to distinct patterns: Cluster 1 (34%) had low inhaler use and high error rates, Cluster 2 (31%) had high inhaler use and high error rates, and Cluster 3 (30%) had overall good adherence. Lung function and co-morbidities were predictive of poor technique, while age and cognition with poor lung function distinguished those with poor adherence and frequent errors in technique. CONCLUSION: These data may inform clinicians both in understanding why a prescribed inhaler is not effective and to devise strategies to promote adherence in COPD

In patients with severe uncontrolled asthma, does knowledge of adherence and inhaler technique using electronic monitoring improve clinical decision making? A protocol for a randomised controlled trial

Introduction: Many patients with asthma remain poorly controlled despite the use of inhaled corticosteroids and long-acting beta agonists. Poor control may arise from inadequate adherence, incorrect inhaler technique or because the condition is refractory. Without having an objective assessment of adherence, clinicians may inadvertently add extra medication instead of addressing adherence. This study aims to assess if incorporating objectively recorded adherence from the Inhaler Compliance Assessment (INCA) device and lung function into clinical decision making provides more cost-effective prescribing and improves outcomes. Methods and analysis: This prospective, randomised, multicentre study will compare the impact of using information on adherence to influence asthma treatment. Patients with severe uncontrolled asthma will be included. Data on adherence, inhaler technique and electronically recorded peak expiratory flow rate will be used to promote adherence and guide a clinical decision protocol to guide management in the active group. The control group will receive standard inhaler and adherence education. Medications will be adjusted using a protocol based on Global Initiativefor Asthma (GINA) recommendations. The primary outcome is the between-group difference in the proportion of patients who have refractory disease and are prescribed appropriate medications at the end of 32 weeks. A co-primary outcome is the difference between groups in the rate of adherence to salmeterol/fluticasone inhaler over the last 12 weeks. Secondary outcomes include changes in symptoms, lung function, type-2 cytokine biomarkers and clinical outcomes between both groups. Cost-effectiveness and cost-utility analyses of the INCA device intervention will be performed. The economic impact of a national implementation of the INCA-SUN programme will be evaluated. Ethics and dissemination:The results of the study will be published as a manuscript in peer-reviewed journals. The study has been approved by the ethics committees in the five participating hospitals. Trial registration NCT02307669; Pre-results

Use of digital measurement of medication adherence and lung function to guide the management of uncontrolled asthma (INCA Sun):a multicentre, single-blinded, randomised clinical trial

BACKGROUND: The clinical value of using digital tools to assess adherence and lung function in uncontrolled asthma is not known. We aimed to compare treatment decisions guided by digitally acquired data on adherence, inhaler technique, and peak flow with existing methods.METHODS: A 32-week prospective, multicentre, single-blinded, parallel, randomly controlled trial was done in ten severe asthma clinics across Ireland, Northern Ireland, and England. Participants were 18 years or older, had uncontrolled asthma, asthma control test (ACT) score of 19 or less, despite treatment with high-dose inhaled corticosteroids, and had at least one severe exacerbation in the past year despite high-dose inhaled corticosteroids. Patients were randomly assigned in a 1:1 ratio to the active group or the control group, by means of a computer-generated randomisation sequence of permuted blocks of varying sizes (2, 4, and 6) stratified by fractional exhaled nitric oxide (FeNO) concentration and recruitment site. In the control group, participants were masked to their adherence and errors in inhaler technique data. A statistician masked to study allocation did the statistical analysis. After a 1-week run-in period, both groups attended three nurse-led education visits over 8 weeks (day 7, week 4, and week 8) and three physician-led treatment adjustment visits at weeks 8, 20, and 32. In the active group, treatment adjustments during the physician visits were informed by digital data on inhaler adherence, twice daily digital peak expiratory flow (ePEF), patient-reported asthma control, and exacerbation history. Treatment was adjusted in the control group on the basis of pharmacy refill rates (a measure of adherence), asthma control by ACT questionnaire, and history of exacerbations and visual management of inhaler technique. Both groups used a digitally enabled Inhaler Compliance Assessment (INCA) and PEF. The primary outcomes were asthma medication burden measured as proportion of patients who required a net increase in treatment at the end of 32 weeks and adherence rate measured in the last 12 weeks by area under the curve in the intention-to-treat population. The safety analyses included all patients who consented for the trial. The trial is registered with ClinicalTrials.gov, NCT02307669 and is complete.FINDINGS: Between Oct 25, 2015, and Jan 26, 2020, of 425 patients assessed for eligibility, 220 consented to participate in the study, 213 were randomly assigned (n=108 in the active group; n=105 in the control group) and 200 completed the study (n=102 in the active group; n=98 in the control group). In the intention-to-treat analysis at week 32, 14 (14%) active and 31 (32%) control patients had a net increase in treatment compared with baseline (odds ratio [OR] 0·31 [95% CI 0·15-0·64], p=0·0015) and 11 (11%) active and 21 (21%) controls required add-on biological therapy (0·42 [0·19-0·95], p=0·038) adjusted for study site, age, sex, and baseline FeNO. Three (16%) of 19 active and 11 (44%) of 25 control patients increased their medication from fluticasone propionate 500 μg daily to 1000 μg daily (500 μg twice a day; adjusted OR 0·23 [0·06-0·87], p=0·026). 26 (31%) of 83 active and 13 (18%) of 73 controls reduced their medication from fluticasone propionate 1000 μg once daily to 500 μg once daily (adjusted OR 2·43 [1·13-5·20], p=0·022. Week 20-32 actual mean adherence was 64·9% (SD 23·5) in the active group and 55·5% (26·8) in the control group (between-group difference 11·1% [95% CI 4·4-17·9], p=0·0012). A total of 29 serious adverse events were recorded (16 [55%] in the active group, and 13 [45%] in the control group), 11 of which were confirmed as respiratory. None of the adverse events reported were causally linked to the study intervention, to the use of salmeterol-fluticasone inhalers, or the use of the digital PEF or INCA.INTERPRETATION: Evidence-based care informed by digital data led to a modest improvement in medication adherence and a significantly lower treatment burden.FUNDING: Health Research Board of Ireland, Medical Research Council, INTEREG Europe, and an investigator-initiated project grant from GlaxoSmithKline.</p

The importance of inhaler adherence in severe asthma and its relationship to clinical outcomes

Patients with asthma who remain troubled with symptoms and asthma attacks despite the use of long acting beta-agonist and inhaled corticosteroid therapy are classed as having severe asthma. Some of these patients have “‘difficult to control’” asthma because of poor adherence or inhaler technique, while others have asthma that is ‘refractory’ to treatment. Identifying and addressing poor adherence to ICS/LABA therapy is essential in management of patients with severe asthma. In clinical trials, adherence assessment ensures that only patients with ‘refractory’ asthma are enrolled and reduces the variance in the results that could result as a consequence of not assessing adherence. In clinical practice assessing and addressing adherence allows appropriate use of biologic therapy. The aim of this thesis was to develop ways to assess adherence to maintenance asthma therapy. Firstly, I conducted a systematic review, investigating whether, and how adherence to inhaled corticosteroids (ICS) and long-acting beta agonist (LABA) is assessed in the screening and run-in phase of randomised controlled trials of ‘add on therapy’ in severe asthma. I found that adherence to ICS/LABA therapy assessment and reporting is rarely done and that the methods used to assess adherence in the randomised controlled trials were inadequate. To overcome these inadequacies, I conducted a randomised clinical trial to assess adherence in patients with severe asthma using the INhaler Compliance Assessment (INCA) device, a digital audio recording device that provides information on inhaler time of use and inhaler technique. I devised pathways that incorporated this information, as well as patient’s symptom scores and peak expiratory flow to design a physician script tailored to optimise asthma treatment. The study assessed the value of using an objective method of assessing inhaler adherence in tailored education therapy and how it guides clinicians to make informed clinical decisions in treating patients with severe asthma

Relationship of inhaler adherence behaviour to clinical outcomes in copd:an observational study

COPD remains a leading cause of healthcare use despite the availability of effective inhaled therapies. We examined adherence to maintenance therapy by assessing the key components of good inhaler use: habit of use and inhaler technique. The relationship between adherence patterns, specific patient characteristics and clinical outcomes at one year was examined. We recruited 226 hospitalised patients with a diagnosis of COPD to this prospective observational study. Inhaler adherence was remotely monitored for 90 days after hospital discharge using an INCATM audio recording device. Cluster analysis grouped patients by their adherence behaviour based on the mean rate of attempted use and critical technique errors. The clinical and psychosocial characteristics of each cluster were examined. The rate of all–cause mortality and healthcare use at 12 months was recorded. Survival analysis was used to evaluate the time to first event across adherence groups. Adherence data was available for 195 patients. We identified four patterns of Adherence behaviour: (1) Regular habit of use and good technique (28%); (2) Regular habit of use and poor technique (21%); (3) Poor habit of use and good technique (33%); (4) Poor habit of use and poor technique (19%). The overall event rate was lowest in Cluster 1, 5.46/person/year. Cluster 2 had the lowest annual rate of hospital presentation, but accounted for the majority of community prescriptions for antibiotics and steroids, mean 4.6/person/ Poster sessions A228 Thorax 2017;72(Suppl 3):A1–278 on 20 June 2018 by guest. Protected by copyright. http://thorax.bmj.com/ Thorax: first published as 10.1136/thoraxjnl-2017-210983.410 on 15 November 2017. Downloaded from year. In an adjusted Cox regression model, Cluster 3 had an increased risk of any adverse outcome compared to Cluster 1, Hazard Ratio 1.8 (1.1–2.9), p=0.02. This group were notable for high anxiety scores and mild cognitive impairment. There was a stepwise increase in mortality across groups, from 11% in Cluster 1% to 33% in Cluster 4, p<0.001. Cluster 4 was older, female, with higher co-morbidity and cognitive impairment. We have identified four clusters of adherence behaviour. There is an association between adherence patterns and clinical outcomes. Each cluster also exhibits distinct clinical and psychosocial traits which may act as drivers of their behaviour. Personalised interventions targeting these specific adherence behaviour patterns may prove a cost-effective strategy to curtail COPD-related healthcare costs

Relationship of inhaler adherence behaviour to clinical outcomes in copd:an observational study

COPD remains a leading cause of healthcare use despite the availability of effective inhaled therapies. We examined adherence to maintenance therapy by assessing the key components of good inhaler use: habit of use and inhaler technique. The relationship between adherence patterns, specific patient characteristics and clinical outcomes at one year was examined. We recruited 226 hospitalised patients with a diagnosis of COPD to this prospective observational study. Inhaler adherence was remotely monitored for 90 days after hospital discharge using an INCATM audio recording device. Cluster analysis grouped patients by their adherence behaviour based on the mean rate of attempted use and critical technique errors. The clinical and psychosocial characteristics of each cluster were examined. The rate of all–cause mortality and healthcare use at 12 months was recorded. Survival analysis was used to evaluate the time to first event across adherence groups. Adherence data was available for 195 patients. We identified four patterns of Adherence behaviour: (1) Regular habit of use and good technique (28%); (2) Regular habit of use and poor technique (21%); (3) Poor habit of use and good technique (33%); (4) Poor habit of use and poor technique (19%). The overall event rate was lowest in Cluster 1, 5.46/person/year. Cluster 2 had the lowest annual rate of hospital presentation, but accounted for the majority of community prescriptions for antibiotics and steroids, mean 4.6/person/ Poster sessions A228 Thorax 2017;72(Suppl 3):A1–278 on 20 June 2018 by guest. Protected by copyright. http://thorax.bmj.com/ Thorax: first published as 10.1136/thoraxjnl-2017-210983.410 on 15 November 2017. Downloaded from year. In an adjusted Cox regression model, Cluster 3 had an increased risk of any adverse outcome compared to Cluster 1, Hazard Ratio 1.8 (1.1–2.9), p=0.02. This group were notable for high anxiety scores and mild cognitive impairment. There was a stepwise increase in mortality across groups, from 11% in Cluster 1% to 33% in Cluster 4, p&lt;0.001. Cluster 4 was older, female, with higher co-morbidity and cognitive impairment. We have identified four clusters of adherence behaviour. There is an association between adherence patterns and clinical outcomes. Each cluster also exhibits distinct clinical and psychosocial traits which may act as drivers of their behaviour. Personalised interventions targeting these specific adherence behaviour patterns may prove a cost-effective strategy to curtail COPD-related healthcare costs