Adherence to single inhaler triple therapy and digital inhalers in Chronic Obstructive Pulmonary Disease: a literature review and protocol for a randomized controlled trial (TRICOLON study).

BACKGROUND: Medication non-adherence is a significant problem in patients with Chronic Obstructive Pulmonary Disease (COPD). Efforts to address this issue are receiving increased attention. Simplifying treatment by prescribing single-inhaler triple therapy (SITT) as an alternative to multi-inhaler triple therapy (MITT) or with smart inhalers are often considered potential solutions. However, the actual impact of these innovations on adherence and clinical outcomes is unclear. METHODS: To address this knowledge gap we first conducted a literature review focusing on two research questions: 1) the difference in adherence between SITT and MITT users in COPD, and 2) the effect of smart inhalers on adherence in COPD. Separate searches were conducted in PubMed and two authors independently assessed the articles. In addition, we present a protocol for a study to acquire knowledge for the gaps identified. RESULTS: To address the first research question, 8 trials were selected for further review. All trials were observational, i.e. randomized controlled trials were lacking. Seven of these trials showed higher adherence and/or persistence in patients on SITT compared with patients on MITT. In addition, four studies showed a positive effect of SITT on various clinical outcomes. For the second research question, 11 trials were selected for review. While most of the studies showed a positive effect of smart inhalers on adherence, there was considerable variation in the results regarding their effect on other clinical outcomes. The TRICOLON (TRIple therapy COnvenience by the use of one or multipLe Inhalers and digital support in ChrONic Obstructive Pulmonary Disease) trial aims to improve understanding regarding the effectiveness of SITT and smart inhalers in enhancing adherence. This open-label, randomized, multi-center study will enroll COPD patients requiring triple therapy at ten participating hospitals. In total, 300 patients will be randomized into three groups: 1) MITT; 2) SITT; 3) SITT with digital support through a smart inhaler and an e-health platform. The follow-up period will be one year, during which three methods of measuring adherence will be used: smart inhaler data, self-reported data using the Test of Adherence to Inhalers (TAI) questionnaire, and drug analysis in scalp hair samples. Finally, differences in clinical outcomes between the study groups will be compared. DISCUSSION: Our review suggests promising results concerning the effect of SITT, as opposed to MITT, and smart inhalers on adherence. However, the quality of evidence is limited due to the absence of randomized controlled trials and/or the short duration of follow-up in many studies. Moreover, its impact on clinical outcomes shows considerable variation. The TRICOLON trial aims to provide solid data on these frequently mentioned solutions to non-adherence in COPD. Collecting data in a well-designed randomized controlled trial is challenging, but the design of this trial addresses both the usefulness of SITT and smart inhalers while ensuring minimal interference in participants' daily lives. TRIAL REGISTRATION: NCT05495698 (Clinicaltrials.gov), registered at 08-08-2022. Protocol version: version 5, date 27-02-2023.

Patient reported medication-related problems, adherence and waste of oral anticancer medication over time.

OBJECTIVES: Patients on oral anticancer therapy regularly experience medication-related problems (MRPs), potentially leading to non-adherence and medication waste. Most studies reporting these experiences have cross-sectional designs. The aim of our study was to explore patient reported MRPs, adherence and waste of oral anticancer medication over time. METHODS: A prospective longitudinal quantitative interview study with 4 months follow-up was performed among patients on oral anticancer medication (mainly tyrosine kinase inhibitors, (anti)hormonal therapy, pyrimidine antagonists) using a semi-structured questionnaire. Patients from two Dutch university medical centres were included from March to December 2022 after informed consent was given. Four interviews were performed with 1 month in between. All interviews were audiotaped, after which the data were entered into an electronic case report form. The primary outcome was the mean number of MRPs per patient per interview round. Secondary outcomes were the proportion of patients with at least one MRP, types of MRPs, perceived non-adherence, medication waste (both in general and specifically for anticancer medication), costs of anticancer medication waste, and factors associated with medication waste as mentioned by the patient. Descriptive statistics were used to analyse the data. RESULTS: Forty patients were included with a mean (SD) age of 64 (9) years; 43% were male. The mean number of MRPs per patient was 2.1 in the first interview and 1.2, 1.0 and 0.9 in the second, third and fourth interviews, respectively. Adverse drug reactions were the most frequently reported type of MRPs (30 (75%) patients in the first interview and 19 (65%) in the last interview). Unintentional non-adherence was regularly reported, especially in the first interview. Medication changes were frequent and associated medication waste was mentioned in all interviews. CONCLUSIONS: Many patients using oral anticancer treatment report MRPs and this number remains substantial over time.

Barriers and Unmet Educational Needs Regarding Implementation of Medication Adherence Management Across Europe: Insights from COST Action ENABLE.

BACKGROUND: Medication adherence is essential for the achievement of therapeutic goals. Yet, the World Health Organization estimates that 50% of patients are nonadherent to medication and this has been associated with 125 billion euros and 200,000 deaths in Europe annually. OBJECTIVE: This study aimed to unravel barriers and unmet training needs regarding medication adherence management across Europe. DESIGN: A cross-sectional study was conducted through an online survey. The final survey contained 19 close-ended questions. PARTICIPANTS: The survey content was informed by 140 global medication adherence experts from clinical, academic, governmental, and patient associations. The final survey targeted healthcare professionals (HCPs) across 39 European countries. MAIN MEASURES: Our measures were barriers and unmet training needs for the management of medication adherence across Europe. KEY RESULTS: In total, 2875 HCPs (pharmacists, 40%; physicians, 37%; nurses, 17%) from 37 countries participated. The largest barriers to adequate medication adherence management were lack of patient awareness (66%), lack of HCP time (44%), lack of electronic solutions (e.g., access to integrated databases and uniformity of data available) (42%), and lack of collaboration and communication between HCPs (41%). Almost all HCPs pointed out the need for educational training on medication adherence management. CONCLUSIONS: These findings highlight the importance of addressing medication adherence barriers at different levels, from patient awareness to health system technology and to fostering collaboration between HCPs. To optimize patient and economic outcomes from prescribed medication, prerequisites include adequate HCP training as well as further development of digital solutions and shared health data infrastructures across Europe.

Usability and feasibility of the Test of Adherence to Inhalers (TAI) Toolkit in daily clinical practice: The BANANA study.

The Test of Adherence to Inhalers (TAI) Toolkit links an adherence measurement instrument (the TAI) to proven effective interventions for different causes of non-adherence to inhaled medication. This study aimed to assess the usability and feasibility of the TAI Toolkit in clinical practice. The TAI Toolkit was piloted in eight primary and secondary care settings. Each study site included 10 patients with asthma and/or COPD and suspected non-adherence. Healthcare professionals (HCPs) recorded clinical data and TAI Toolkit outcomes. Data on usability and feasibility were collected in semi-structured interviews and with the System Usability Score (SUS). Of the included patients, 81% were non-adherent, and sporadic non-adherence was the most common (69%). The TAI Toolkit was valued with a mean SUS-score of 85.9 by the HCPs. They found the toolkit to 'be visually attractive', 'easy-to-use' and 'give insight into patients' adherence', thereby offering good potential for its use in clinical practice.

DIGIPREDICT: physiological, behavioural and environmental predictors of asthma attacks-a prospective observational study using digital markers and artificial intelligence-study protocol.

INTRODUCTION: Asthma attacks are a leading cause of morbidity and mortality but are preventable in most if detected and treated promptly. However, the changes that occur physiologically and behaviourally in the days and weeks preceding an attack are not always recognised, highlighting a potential role for technology. The aim of this study 'DIGIPREDICT' is to identify early digital markers of asthma attacks using sensors embedded in smart devices including watches and inhalers, and leverage health and environmental datasets and artificial intelligence, to develop a risk prediction model to provide an early, personalised warning of asthma attacks. METHODS AND ANALYSIS: A prospective sample of 300 people, 12 years or older, with a history of a moderate or severe asthma attack in the last 12 months will be recruited in New Zealand. Each participant will be given a smart watch (to assess physiological measures such as heart and respiratory rate), peak flow meter, smart inhaler (to assess adherence and inhalation) and a cough monitoring application to use regularly over 6 months with fortnightly questionnaires on asthma control and well-being. Data on sociodemographics, asthma control, lung function, dietary intake, medical history and technology acceptance will be collected at baseline and at 6 months. Asthma attacks will be measured by self-report and confirmed with clinical records. The collected data, along with environmental data on weather and air quality, will be analysed using machine learning to develop a risk prediction model for asthma attacks. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the New Zealand Health and Disability Ethics Committee (2023 FULL 13541). Enrolment began in August 2023. Results will be presented at local, national and international meetings, including dissemination via community groups, and submission for publication to peer-reviewed journals. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry ACTRN12623000764639; Australian New Zealand Clinical Trials Registry.

Cost-Effectiveness and Impact on Health Care Utilization of Interventions to Improve Medication Adherence and Outcomes in Asthma and Chronic Obstructive Pulmonary Disease: A Systematic Literature Review.

BACKGROUND: Poor adherence to asthma and chronic obstructive pulmonary disease maintenance therapies impairs health outcomes. Proven and cost-effective programs to promote adherence and persistence are not yet in regular widespread use. Implementation costs are a potential barrier to uptake of such programs. OBJECTIVE: We undertook a systematic literature review and narrative synthesis of studies investigating the cost-effectiveness of treatment adherence-promoting programs or that determined their impact on health care budget directly or via health care resource use (HCRU). METHODS: We identified relevant publications using Medline and PreMEDLINE (PubMed), Embase (Embase.com, Elsevier), and EconLit for publications between January 2000 and July 2021. We also searched clinical trial databases and selected conference proceedings. RESULTS: Of 1,910 potentially relevant articles, 26 met prespecified inclusion criteria and underwent data extraction. Eleven reported a direct assessment of adherence, 15 included economic evaluations, and 17 described HCRU. None included an analysis of biologic medication use. When they were studied, interventions were often found to be highly cost-effective, with dominant incremental cost-effectiveness ratios in some cases. Reductions in direct costs and HCRU (health care visits, hospital admissions, and/or the use of medications, including add-on/reliever treatment and antibiotics) were frequently reported. Reported use of maintenance treatments improved in some studies. Counseling and/or digitally informed programs were used in all cases in which favorable outcomes were observed. CONCLUSIONS: Adherence-promoting interventions are mostly cost-effective and often result in reduced HCRU and associated costs. Multidisciplinary care involving one-to-one advice and digitally enhanced communications appear to offer the greatest benefit.

Factors Associated with Patient Trust in the Pharmacy Team: Findings from a Mixed Method Study Involving Patients with Asthma & COPD.

Purpose: The pharmacy team has been shifting its role from primarily dispensing medications to providing patient-centred pharmaceutical care. Establishing a trust relation between the pharmacy team and their patients is fundamental for this new role. This study aimed to (i) identify the level of trust in the pharmacy team among patients with asthma and/or COPD, (ii) assess whether the level of trust patients have in pharmacists differs from their trust in pharmacy technicians, and (iii) identify factors that contribute to building trust in the pharmacy team. Patients and Methods: First, a focus group with six patients with asthma and/or COPD was conducted to explore which aspects they considered significant for establishing trust in the pharmacy team. Subsequently, these insights were used to develop an online questionnaire. A link to the online questionnaire was distributed among patients with asthma and/or COPD. Data were analysed using exploratory factor analyses to identify underlying constructs for trust. Regression analyses were conducted to evaluate whether these constructs affected trust (scale 1-10) in the pharmacy team. Results: A total of 290 patients completed the questionnaire. On average, they rated their trust in the pharmacy team with a score of 7.4 out of 10 (SD: 1.5), almost identical to their trust in the pharmacist and pharmacy technician. Patient trust in pharmacy teams is influenced by their perception of engagement, expertise in medication-related matters, and effective communication. Conclusion: Trust in the pharmacy team was observed as moderately high, indicating that there is room for improvement. Due to the changing role of the pharmacy team, its members should strive to enhance their patient-centred skills ensuring ongoing efforts to build and maintain trust with patients.

Shared decision making and medication adherence in patients with COPD and/or asthma: the ANANAS study.

Background: Medication adherence to inhalation medication is suboptimal in patients with COPD and asthma. Shared decision making (SDM) is proposed as an intervention to improve medication adherence. Despite its wide promotion, evidence of SDM's association with greater medication adherence is scarce. Also, it is unknown to what degree patients presently experience SDM and how it is associated with medication adherence. Objective: To (i) assess the level of SDM and (ii) medication adherence, (iii) explore the relation between SDM and medication adherence and iv) investigate possible underlying mechanisms. Methods: Cross-sectional observational study. A survey was distributed among Dutch patients with COPD and/or asthma using inhaled medication. Medication adherence was measured using the Test of Adherence to Inhalers (TAI-10), and SDM by the 9-item Shared Decision-Making questionnaire (SMD-Q-9). Feeling of competence, relatedness and feeling of autonomy from the Self-Determination Theory (SDT) were considered as possible mechanisms. The primary outcome was adherence. Results: A total of 396 patients with complete information on relevant covariates were included. Mean SDM-Q-9 score was 26.7 (SD 12.1, range 0-45) and complete adherence was 41.2%. The odds ratio for the association of SDM with adherence was 1.01 (95% CI: 0.99, 1.02). This only changed minimally when adjusted for mediators (mediating effect <3%). Conclusion: The patient experienced level of SDM in daily practice and medication adherence have room for improvement. No association between SDM and medication adherence was observed. Factors related to feeling of competence, relatedness and feeling of autonomy did not meaningfully explain this finding.

Multidisciplinary tuberculosis care: leveraging the role of hospital pharmacists.

INTRODUCTION: Optimal pharmacological treatment of tuberculosis (TB) requires a multidisciplinary team, yet the hospital pharmacist's role is unclear. We aimed to analyse hospital pharmacist-provided clinical pharmacy services (CPS) implementation in TB care. METHOD: A nationwide survey-based online cross-sectional study was conducted on hospital pharmacists in Indonesia from 1 November 2022 to 22 November 2022. Outcomes were the extent of pharmacists' involvement in multidisciplinary TB care, TB-related CPS provided and views on TB-related CPS. The probability of pharmacists' involvement in multidisciplinary TB teams was assessed using logistic regression. RESULTS: In total, 439 pharmacists (mean age 31.2±6.22 years, 78% female) completed the survey. Thirty-six per cent were part of multidisciplinary TB care, and 23% had TB-related tasks. Adherence monitoring (90%) and drug use evaluation (86%) were the most conducted TB-related CPS. Pharmacists' views on TB-related CPS implementation were generally positive, except for financial incentives. Work experience (OR 1.99, 95% CI 1.09 to 3.61), ever received TB-related training (OR 3.51, 95% CI 2.03 to 6.14) and specific assignments to provide TB-related CPS (OR 8.42, 95% CI 4.99 to 14.59) significantly increased pharmacist involvement in multidisciplinary TB care. CONCLUSION: Around one-third of hospital pharmacists are part of multidisciplinary TB care, with medication adherence and drug use monitoring as primary tasks. Pharmacists' experience, training, assignment to provide TB-related CPS and financial incentives are key elements for further implementation in multidisciplinary TB care. Pharmacists should proactively support current TB care and conduct operational research, sharing data with healthcare peers and fostering a collaborative multidisciplinary TB care team.

Adult Severe Asthma Registries: A Global and Growing Inventory.

Aim: The International Severe Asthma Registry (ISAR; http://isaregistries.org/) uses standardised variables to enable multi-country and adequately powered research in severe asthma. This study aims to look at the data countries within ISAR and non-ISAR countries reported collecting that enable global research that support individual country interests. Methods: Registries were identified by online searches and approaching severe asthma experts. Participating registries provided data collection specifications or confirmed variables collected. Core variables (results from ISAR's Delphi study), steroid-related comorbidity variables, biologic safety variables (serious infection, anaphylaxis, and cancer), COVID-19 variables and additional variables (not belonging to the aforementioned categories) that registries reported collecting were summarised. Results: Of the 37 registries identified, 26 were ISAR affiliates and 11 non-ISAR affiliates. Twenty-five ISAR-registries and 4 non-ISAR registries reported collecting >90% of the 65 core variables. Twenty-three registries reported collecting all optional steroid-related comorbidity variables. Twenty-nine registries reported collecting all optional safety variables. Ten registries reported collecting COVID-19 variables. Twenty-four registries reported collecting additional variables including data from asthma questionnaires (10 Asthma Control Questionnaire, 20 Asthma Control Test, 11 Asthma Quality of Life Questionnaire, and 4 EuroQol 5-dimension 5-level Questionnaire). Eight registries are linked to databases such as electronic medical records and national claims or disease databases. Conclusion: Standardised data collection has enabled individual severe asthma registries to collect unified data and increase statistical power for severe asthma research irrespective of ISAR affiliations.

New terminology of medication adherence enabling and supporting activities: ENABLE terminology.

Introduction: Medication non-adherence negatively affects the effectiveness of evidence-based therapies and sustainability of healthcare systems. Lack of agreed terminology of medication adherence enabling and supporting activities leads to underuse of the available tools. The ENABLE COST Action was aimed at proposing a new terminology for these activities in order to help both scientific research and its clinical application. Methods: Initial discussions within the ENABLE Working Groups allowed for the conceptualization of four interlinked terms related to adherence, i.e., "medication adherence technology", "medication adherence enhancing intervention", "best practice" and "reimbursement". The iterative process of internal discussion was structured around two dedicated international workshops. Moreover, extensive stakeholder consultations have been organised, including an interactive online survey used to assess the level of agreement with, and the clarity of relevant terms and definitions proposed. Results: Detailed analysis of the results of this process allowed for fine-tuning of the items, and finally, for proposing the final set of definitions. Across all the three phases of this process, the definitions were substantially modified to better reflect the concepts, simplify the language, and assure completeness and cohesiveness of terminology. Feedback obtained from the stakeholders helped this process and confirmed that the final terms and definitions were well received by the experts active in the field of medication adherence. Discussion: Covering the gap in the existing terminology, this work proposes a cohesive set of terms and definitions applicable to medication adherence enabling and supporting activities. Promoting evidence-based approach to this field, this terminology may help research, clinical practice and policy.

The impact of trust in healthcare and medication, and beliefs about medication on medication adherence in a Dutch medication-using population.

INTRODUCTION: Trust in healthcare and medication, defined as feelings of reassurance and confidence in the healthcare system or medication, may be a key prerequisite before engaging in the use of medication. However, earlier studies have focussed on beliefs about medication rather than trust as predictors of medication adherence. This study therefore aims to simultaneously explore the relationship of trust in healthcare, medication and beliefs about medication, with medication adherence. METHODS: In a cross-sectional study, an online questionnaire was sent out to 1500 members of the Dutch Health Care Consumer Panel of Nivel in November 2018. Respondents were asked to grade their level of trust in healthcare and medication (scale 1-10). The Beliefs About Medicines Questionnaire (BMQ) for general and specific medication beliefs was used to address beliefs, the Medication Adherence Report Scale (MARS-5) to measure medication adherence. Data were analysed using structural equation modelling (SEM) with a backward stepwise approach. Out of 753 people that completed the questionnaire, 407 people used prescription medication and were included in the analyses. RESULTS: A positive association between trust in medication and medication adherence was found (0.044, p < 0.05). BMQ subscales Overuse (-0.083, p < 0.05), Necessity (0.075, p < 0.05) and Concerns (-0.134, p < 0.01) related with medication adherence. BMQ subscale Harm did not relate to medication adherence. CONCLUSION: Trust in medication and beliefs about medication were both individually associated with medication adherence. Healthcare providers should therefore not only focus on patients' medication beliefs, but also on strengthening patients' trust in medication to improve medication adherence.

Implementing an Evidence-Based COPD Hospital Discharge Protocol: A Narrative Review and Expert Recommendations.

Discharge bundles, comprising evidence-based practices to be implemented prior to discharge, aim to optimise patient outcomes. They have been recommended to address high readmission rates in patients who have been hospitalised for an exacerbation of chronic obstructive pulmonary disease (COPD). Hospital readmission is associated with increased morbidity and healthcare resource utilisation, contributing substantially to the economic burden of COPD. Previous studies suggest that COPD discharge bundles may result in fewer hospital readmissions, lower risk of mortality and improvement of patient quality of life. However, evidence for their effectiveness is inconsistent, likely owing to variable content and implementation of these bundles. To ensure consistent provision of high-quality care for patients hospitalised with an exacerbation of COPD and reduce readmission rates following discharge, we propose a comprehensive discharge protocol, and provide evidence highlighting the importance of each element of the protocol. We then review care bundles used in COPD and other disease areas to understand how they affect patient outcomes, the barriers to implementing these bundles and what strategies have been used in other disease areas to overcome these barriers. We identified four evidence-based care bundle items for review prior to a patient's discharge from hospital, including (1) smoking cessation and assessment of environmental exposures, (2) treatment optimisation, (3) pulmonary rehabilitation, and (4) continuity of care. Resource constraints, lack of staff engagement and knowledge, and complexity of the COPD population were some of the key barriers inhibiting effective bundle implementation. These barriers can be addressed by applying learnings on successful bundle implementation from other disease areas, such as healthcare practitioner education and audit and feedback. By utilising the relevant implementation strategies, discharge bundles can be more (cost-)effectively delivered to improve patient outcomes, reduce readmission rates and ensure continuity of care for patients who have been discharged from hospital following a COPD exacerbation.

Electronic monitoring with a digital smart spacer to support personalized inhaler use education in patients with asthma: The randomized controlled OUTERSPACE trial.

BACKGROUND: Poor adherence to inhaled medication has been associated with poor outcomes. Smart spacers can monitor inhaler use and technique, yet their feasibility in adults with asthma and their potential benefits are unknown. OBJECTIVE: Assessing the feasibility of undertaking a definitive randomized controlled trial (RCT) of smart spacer-based inhaler education and explore potential clinical benefits in adults with asthma. METHODS: Two-month randomized controlled feasibility OUtcomes following Tailored Education and Retraining: Studying Performance and AdherenCE (OUTERSPACE) trial comparing personalized smart spacer-based inhaler education versus usual care. Patients were recruited in four Dutch primary care centres. Outcomes were feasibility (inclusion speed, patient acceptance), medication adherence, inhaler technique, clinical effects (lung function, ACQ, FeNO) and usability (System Usability Scale [SUS]). RESULTS: 42 patients were randomized and all completed the study. The feasibility of performing a larger trial focusing on asthma patient education using a smart spacer was demonstrated with all patients included in four months and a participation rate of 86%. In the intervention group, inhalation errors per day decreased by 26.2% while in the usual care group inhalation errors increased by 14.6% (p = 0.021). Adherence decreased slightly in the intervention group as opposed to improvement in the control group (difference 12%, p = 0.028). No changes in lung function, ACQ or FeNO were observed. Usability was deemed high (SUS patients 71, nurses 89). CONCLUSION: This RCT showed that smart spacer-driven education in patients with asthma is feasible and in this short-term study reduced inhaler errors. Longer-term and larger studies are required to assess clinical effects.