Plain English Summary
Background and study aims
How well a patient takes their medication as prescribed, usually referred to as adherence, is a widespread issue affecting patients irrespective of their condition or type of treatment. Poor adherence to medication can lead to persistent symptoms, poor control of disease, reduced quality of life and poor health outcomes for patients. In the case of Chronic Obstructive Pulmonary Disease (COPD), patients who do not take their COPD medication (inhaler) as prescribed can result in a worsening of symptoms, increased risk of lung infections and increased risk of hospital visits and admissions. Treatment guidelines recommend that poor adherence and inhaler technique of patients should be addressed before changing or increasing the medication prescribed. A common reason for poor adherence is that patients simply forget to take their medication. New technologies are now available that can be used to remind patients to take their medication. In a survey by the COPD Foundation, 66% of patients reported that they would like a tool to help them track their medication use. Previous studies in asthma have shown the benefits of inhaler reminders in reducing forgetfulness and improving health outcomes for patients. However, no similar studies have been conducted in patients with COPD. The challenge with assessing adherence in research studies is that if patients are aware that they are participating in a study, this can influence their behaviour and increase their adherence. Adherence and its impact on patient outcomes can only be reliably assessed in studies that resemble real life as closely as possible. Various inhalers are available for the daily management of COPD. New technology to support taking medication has been introduced for the Ultibro Breezhaler inhaler. This technology consists of a sensor device that a patient will attach directly to the inhaler, and a mobile phone application (‘app’) that connects with the sensor device through a wireless Bluetooth connection. The sensor detects and records when a patient inhales and the mobile app also reminds them if they have not taken their daily medication. This technology, developed by Propeller Health, is currently available in the UK through healthcare providers (including GP practices) taking part in a programme with Propeller Health. The aim of this study is to find out whether this technology can improve the treatment and clinical outcomes of people with COPD.
Who can participate?
Patients with COPD and poor adherence to treatment
What does the study involve?
This study aims to recruit over 176 GP practices in the UK and collect non-identifiable or anonymous data for 1,312 patients from the electronic medical records of participating practices. Half of the participating practices are randomly allocated to receive access to the adherence support technology and offer the sensor device plus mobile app to suitable patients with COPD. The other half of the participating practices continue their usual routine patient care for their patients with COPD without providing adherence support technology. The study does not require patients to attend their GP practice outside of their usual routine care. Each practice takes part in the study for 12 months and anonymous data is extracted from their electronic medical records at the beginning of the study and regularly until the end of the study. All data are stored in a research ethics approved database – Optimum Patient Care Research Database (https://opcrd.co.uk).
What are the possible benefits and risks of participating?
The results from this study are expected to provide real life evidence that provision of adherence support technologies can provide benefits in patients with COPD. The results from this and other studies can be expected to help patients and healthcare professionals make better decisions about their treatment to improve patient health and quality of life, and reduce healthcare costs associated with the treatment of patients. The trial will have no impact on patients at the participating sites allocated to the control group as they will continue to receive their usual care. The researchers therefore do not expect there to be any risks or benefits to these patients. Similarly, at the sites allocated to the adherence support, patients will continue to receive their usual care, but commercially available adherence technology devices will be made available to these GP practices at no cost. The sites will then be able to offer this technology to patients who are suitable for and might benefit from adherence support, i.e. patients with poor adherence and frequent exacerbations who are clinically suitable for a dual bronchodilator therapy with Ultibro. Indeed, the correct intervention according to treatment guidelines for these patients is to address adherence and inhaler technique, not to step up therapy. The researchers do not expect the study to have any risks or benefits to those patients who do not receive the adherence device. If the patient receives the device, this may help improve their treatment adherence, which could then improve their clinical outcomes.
Where is the study run from?
Observational and Pragmatic Research International Ltd (UK)
When is the study starting and how long is it expected to run for?
April 2019 to February 2022
Who is funding the study?
Who is the main contact?
Ms Ellen Ashmore
Ms Ellen Ashmore
5 Coles Lane
+44 (0)1223 967855
A pragmatic, cluster randomized trial evaluating the impact of an enhanced adherence package (dual bronchodilator + add-on + app) on time to treatment failure and other clinical outcomes in exacerbating COPD patients with poor adherence to mono or dual therapy over one year
Can technology use improve the treatment and clinical outcomes in people with Chronic Obstructive Pulmonary Disease (COPD)?
Not taking medications as prescribed is an issue affecting patients irrespective of disease and treatment type and can lead to poor clinical outcomes such as worsening symptoms. In COPD, guidelines have noted the importance of supporting patients with their regular inhaler use as part of COPD management. The study will focus on patients with COPD that have poor treatment adherence and frequent flare-ups often triggered by cold or similar events.
Approved 06/11/2019, East Midlands - Derby Research Ethics Committee (The Old Chapel, Royal Standard Place, Nottingham, NG1 6FS, UK; Tel: +44 (0)207 104 8109; Email: email@example.com), REC ref: 19/EM/0238, IRAS: 260690
Pragmatic cluster randomized trial
Primary study design
Secondary study design
Cluster randomised trial
Patient information sheet
Not available in web format, please use contact details to request a participant information sheet
Chronic obstructive pulmonary disease (COPD)
This is a pragmatic real-life study which does not involve any study visits outside routine care. All patient contact and visits during the study will be part of routine COPD management at the patients’ own GP practice, in accordance with NICE recommendations which state that patients with mild/moderate/severe COPD should be reviewed at least once a year. The hypothesis is that patients at sites that have availability of adherence support technology together with the Ultibro inhaler, will demonstrate better clinical outcomes than patients at sites that continued their usual routine care without access to the adherence support technology. The researchers will use anonymised data extracted from 176 GP practices’ electronic health records to assess the study outcomes. Data will be extracted by Optimum Patient Care (OPC) who are an organization specialized in primary care data extraction.
The study will be randomised on a practice-level, which means that instead of randomising individual study participants, the researchers will randomise the participating sites. Randomization will be stratified according to practice size, deprivation score and the percentage of patients with COPD with a record of FEV1 in the preceding 12 months. Sites will be randomised in 1:1 ratio to the control arm or to the adherence support arm (ASA). As this study aims to collect real-life data on the impact of Ultibro + adherence technology, sites in the control arm will continue to administer their usual routine care. Particularly for studies looking at real-life impact, a cluster randomised study design can offer various benefits over a traditional randomised controlled trial (RCT) design, where individual patients (rather than sites or clusters) are randomised. Firstly, in a traditional RCT the same investigator is treating patients in both treatment groups. This can result in contamination. For example, in the case of this study, in a traditional RCT setting the same doctor would be required to offer adherence support to some of their patients, while providing usual care for others. It is likely that the “usual care” provided by this doctor could be affected by the fact that they have received training on the adherence support technology and are therefore more aware of adherence issues. Second, traditional RCTs usually require that all study participants are informed and consenting volunteers. This requirement likely pre-selects individuals who are at a lower risk for non-adherence, particularly for RCTs of behavioural interventions. Indeed, patients enrolling in clinical trials may be systematically different regarding adherence levels than those declining to participate. Furthermore, the clinical trial process means that patients are fully aware of adherence monitoring, and such knowledge could result in patients modifying their adherence behaviour.
The following steps will take place at the participating sites:
1. Medical record data will be extracted by OPC to collect baseline data
2. Using the extracted data, OPC will run an algorithm to obtain a list of patients that meet the study suitability criteria at each site. The list will contain unique identifiers which can only be linked to identifiable patient information at the GP practice
3. Each site is randomized to treatment arm centrally by the Sponsor’s research team
4. If the site is randomised to the control arm, they will continue their usual routine care
5. If the site is randomised to the adherence support arm (ASA), they will be provided with the Propeller Health adherence support devices and will be trained on its use and functionalities by the Sponsor or by Propeller Health. The site will then be able to offer this technology to their patients identified as suitable (by the OPC algorithm). A specific read code for inhaler aid device should be recorded in patient notes for any patients provided the adherence support device.
6. At the end of the study, data from all sites will be extracted to obtain the data for the 12-month outcome period
OPC will provide support to practices in both arms and this includes mail out, or administration at routine COPD review appointments, of Optimum Patient Care (OPC) COPD review questionnaire to patients with COPD. The questionnaire includes a question about whether the patient would use an inhaler that can send reminders on a smartphone, if this was available. Those patients in the control arm that respond Yes to this question, would be considered to represent a matching population to those patients in ASA arm who accepted the adherence technology. This allows us to define the comparator group for the primary analysis.
Other data collected with the review questionnaire by OPC will not be shared with the Sponsor. The questionnaire will only be sent out at 12 months at the control group sites in order to eliminate any impact that completing this questionnaire could have on patient behaviour and adherence. At ASA sites, this questionnaire can be administered at Baseline COPD reviews at discretion of the site, but the data will not be used for the purposes of this study and will not be shared with the Sponsor. The sites will be required to sign an agreement with OPC for the collection and use of COPD review questionnaire data. This agreement is separate to the main study agreement with the Sponsor.
At the GP sites randomised to the adherence support arm, data from patients meeting the following criteria will be included in the primary endpoint analysis: clinically suitable (see above), and accepted the Package (i.e. Ultibro + Add-on device+App) at Baseline (these patients will be identified by a specific read code for inhaler aid device).
At the control GP sites, data from patients meeting the following criteria will be included in the primary endpoint analysis: clinically suitable (see above), willing to accept the technology*, and received LABA/LAMA, LABA, LAMA or LABA/ICS at Baseline.
*At the control GP sites willingness is determined at the end of the study by assessing the acceptance of technology of the clinically suitable patients. This will be determined by a question in the OPC COPD review questionnaire: If an inhaler was available with technology providing reminders on a smartphone when to take your COPD treatment, would you use it? In order to match the primary populations in the two arms as closely as possible (in terms of both willingness and ability), the response options include “I do not have a smartphone”.
Primary outcome measure
The primary endpoint is time to treatment failure. Data will be collected from electronic medical health records. Time to treatment failure is defined as the time (in whole days) from baseline to the first occurrence of:
1. Moderate/severe COPD exacerbation, requiring: an acute oral corticosteroid course prescription, antibiotics prescribed with evidence of a lower respiratory consultation at the same day, respiratory-related hospital attendance/admission (based on GP medical record data), or respiratory-related A&E/ER attendance (based on GP medical record data)
2. Escalation of therapy to triple therapy (ICS/LABA/LAMA)
3. Prescription of additional chronic therapy for COPD (i.e. theophylline or other methylxanthines, maintenance oral corticosteroids, PDE4 inhibitors, macrolides (e.g. Azithromycin, Erythromycin), mucolytics (e.g. carbocysteine, N-acetylcysteine), or any other respiratory medication prescribed for COPD)
4. Respiratory-related death
Secondary outcome measures
1. Adherence, determined as Medication Possession Ratio (MPR) based on electronic medical record data at 12 months
2. Proportion of patients with moderate/severe exacerbations, and total number of exacerbations at 12 months, based on electronic medical record data, where exacerbation is defined as requiring: an acute oral corticosteroid course prescription, antibiotics prescribed with evidence of a lower respiratory consultation at the same day, respiratory-related hospital attendance or admission (based on GP medical record data), or respiratory-related A&E/ER attendance (based on GP medical record data)
Overall trial start date
Overall trial end date
Reason abandoned (if study stopped)
Participant inclusion criteria
For a practice to be eligible for participation, the following criteria should be met:
1. Willing to receive OPC clinical audit and quality improvement services, including IT access for secure software installation and de-identified data extraction
2. Willing to use adherence technology as part of clinical practice
3. At least 16 patients suitable for adherence technology support (see below)
4. A clinician (doctor, nurse, pharmacist, etc) willing to act as a practice lead
5. Prescribing or able to prescribe Ultibro® Breezehaler® as a routine clinical care option i.e. inhaler compatible with the add-on technology
Patients suitable for adherence technology support:
1. Confirmed COPD diagnosis
2. Smoking history
3. At least 2 COPD exacerbations in the last 24 months
4. Poor adherence to single/dual COPD therapy – Total adherence to current mono/dual therapy of ≤50% based on refill Rx data in the last 12 months
Target number of participants
704 patients from each arm of the study will be participating (1408 patients from the 176 GP practices)
Participant exclusion criteria
GP Practice who cannot prescribe Ultibro breezhaler or currently do not prescribe Ultibro breezhaler
Recruitment start date
Recruitment end date
Countries of recruitment
Trial participating centre
Observational and Pragmatic Research International Ltd
Stubbs House Stubbs Green, Loddon
Observational and Pragmatic Research International Ltd
Stubbs House Stubbs Green
+44 (0)1223 967855
Novartis AG, Novartis International AG
Funding Body Type
private sector organisation
Funding Body Subtype
For-profit companies (industry)
Results and Publications
Publication and dissemination plan
1. The study protocol will be made available after the study’s ethics approval
2. Abstract for European Respiratory Society conference 2021
3. Manuscript publication in a high impact respiratory journal
IPD sharing statement
The datasets generated and/or analysed during the current study are not expected to be made available due to restrictions on the use of the Optimum Patient Care Research Database (study data source), as outlined within the legally binding data-sharing agreement with the study sponsor. Individual requests for dataset access may be made available for approved researchers on specific requests to the steering committee and with the written approval for data sharing by the ADEPT committee (governing body of OPCRD).
Intention to publish date
Participant level data
Not expected to be available
Basic results (scientific)