sTep dOwn inhalers in the reAl WorlD (TOWARD)
Research type
Research Study
Full title
sTep dOWn inhAlers in the Real worlD (TOWARD)- a feasibility study of prudent prescribing for Chronic Obstructive Pulmonary Disease
IRAS ID
212862
Contact name
Joseph Annandale
Contact email
Sponsor organisation
Hywel Dda University Health Board
Duration of Study in the UK
2 years, 11 months, 1 days
Research summary
Summary of Research
Current guidelines for chronic obstructive pulmonary disease (COPD) recommend treatment with inhaled corticosteroids (ICS) in combination with long-acting bronchodilators for certain people. However most studies suggest ICS are over prescribed in COPD, the benefits of ICS remain under debate and their side effects and prescribing costs are considerable. Recent research in tightly controlled trials suggests reducing then stopping ICS is not associated with worse outcome if long acting bronchodilators are maintained and even that new combined bronchodilators alone may actually be more effective, safer and significantly cheaper than traditional inhalers containing ICS. Official guidelines have not yet reflected this new evidence as they can take many years (last NICE were updated in 2010) and a real world study, reflecting standard services (outside specialist pharma-sponsored studies) would greatly inform national guidelines.
We want to test the feasibility of a ICS withdrawal protocol initially in 80 patients with stable COPD, in a real-world study. Patients prescribed ICS will be given the choice of one of 4 new (licensed) inhalers containing the combined bronchodilators, hence not limiting it to any one brand and ensuring they are able to use the device to deliver the drug effectively into the lungs. They will be advised to keep on these new inhalers for at least 12 months and stop their ICS; we will follow participants at set intervals over 12 months. All other standard care will continue. We will assess the uptake and maintenance rates of this switch and record safety, symptom control, lung tests and prescribing costs. These will help inform the practicality of implementing a large scale ICS inhaler change across several predominantly Primary Care sites.Summary of Results
Title:
Step down inhalers in the real world (TOWARD)
Background:
This research study was carried out by Prof Keir Lewis and Joe Annandale with researchers within Hywel Dda University Health Board in South West Wales. The study was sponsored by the Health Board and developed in collaboration with Swansea University. It started in May 2017 and ran until August 2021.
This was a small test study to see if our approach for changing inhalers was feasible and if a larger study would be possible. We wanted to know if our health community would support the study, if there were enough people eligible and wanting to take part in our study, and if we could collect the data we needed to measure relevant clinical outcomes.
All participants had to have a diagnosis of chronic obstructive pulmonary disease (COPD) with no history or features of asthma. COPD is a condition that results in long term symptoms such as breathlessness and cough. Lung infections in people with COPD can cause flare ups (exacerbations), which sometimes require hospitalisation. COPD is primarily caused by cigarette smoking. Treatments include drugs known as bronchodilators, which open up the narrow airways and reduce symptoms, and inhaled steroids, which can reduce the number of exacerbations. These drugs are delivered directly to the lungs in inhaler devices. Participants in this study had to be taking two different bronchodilators and an inhaled steroid in two different devices. Potential participants were identified from hospital chest clinics and primary care COPD registers.
Why we wanted to undertake this research:
Inhaled steroids are recommended (indicated) for use in people with COPD who have frequent exacerbations or admissions to hospital. Inhaled steroids are often prescribed outside of their recommended use, despite having potential side effects and incurring a financial cost. The study wanted to explore stopping inhaled steroids in people with COPD who had not had a recent exacerbation or hospital admission. Other studies have shown inhaled steroids can be stopped safely but these studies were in very specific patient groups and not typical of the patients we meet every day in our practice. If we knew that inhaled steroids could be stopped safely, it would reduce any side effect risks and reduce a financial burden.
In the study, participants were also given the choice of which inhaler device they liked (from four options) and providing they could use it effectively were prescribed their chosen device. Involving people in their care and giving choice may improve how regularly they take their treatment, and in turn, improve their symptoms and quality of life.
What happened in the study:
Participants were screened for eligibility and consented in line with all ethical guidelines and approved research protocols. At their initial visit patient demographics were recorded, together with current medications and medical history. A breathing test (spirometry) was undertaken and two validated quality of life questionnaires were completed; one specific to COPD (COPD assessment test, or CAT) and one generic (EQ-5D-5L). Participants were shown four inhaler device options, asked to select their preferred device and the lung nurse checked they could use it effectively. Each of the four devices contained two bronchodilators but no inhaled steroid, reducing the number of inhaler devices participants had to use from two to one.
This was an open study so everybody (participant, clinical team, research team) knew what new medication the participant was taking. Following the step-down of inhalers, the research team monitored what happened to each participant over the 12 month study period, and participants’ primary care providers knew that their inhalers (or any medication) could be changed at any point, for any appropriate reason, during the study.
Initially participants returned for follow up visits at 4, 12, 26 and 52 weeks but this was reduced, following appropriate approvals, to 4 and 52 weeks only. This was more in keeping with normal day-to-day clinical practice, where an individual would have a change in medication, return after a few weeks to review any issues, and return for routine review 12 months later.
At follow up, participants repeated the breathing test and questionnaires, any changes to their general health or medications were recorded and their inhaler technique was rechecked. For each participant, the number of exacerbations or hospitalisations during the 12 month study period, compared to the 12 months prior to participating in the study, was recorded.
A total of 66 participants were recruited to the study. 60 participants completed the full 12 month study period. 43 participants were men and the average age of participants was 70 years old. The average lung function of participants was 49% of predicted. Analysis of the CAT questionnaire scores showed that symptoms were a significant burden for participants. Out of a maximum (and worst possible) score of 40, the average score of participants was 22.6. Only 12 participants were current smokers.
Results:
The feasibility of the study was assessed against a series of targets agreed in advance. Most primary care practices were happy to support the study (93%) but none were able to offer any health professional time to be trained or to undertake study activities. Recruitment fell well below the 50% target of eligible participants recruited, with only 23% of those invited recruited, which represented 3% of the total number of patients screened as eligible. Key data capture was high (86-89% against a target of >60%) due to the high number completing the study (91% of participants).
56% of participants did not restart their inhaled steroid during the study period, against a target of 80%. Within the study period there was a 33% increase in the number of exacerbations against a target of 20%. 42% of CAT scores and 44% of EQ-5D-5L scores indicated no worsening quality of life (against a target of >49%).
The overall exacerbation rates did increase, by 0.52 exacerbations per participant, within the 12 month study period, but this was not statistically significant. There was a significant increase in hospital admissions but the underlying numbers were very low and increased from 0.05 hospital admissions per participant/year to 0.2. There was no significant change in lung function or quality of life, measured via the questionnaires.
Analysis of the data showed there were three significant predictors influencing the likelihood of someone restarting an inhaled steroid. Participants were more likely to restart if they had experienced two or more exacerbations in the previous 12 months, if their lung function was less than 50% predicted, and if they lived alone.
All inhaler devices were chosen by at least one participant. The main reasons given for choosing a particular device were ease of use, and it needing to be taken only once a day. 56% of participants chose a new device, 21% of participants chose a device they had used previously and 23% of participants chose a device similar to one they had used previously. Adherence improved significantly, as measured by inhaler prescription pick-up rate, increasing from 86% to 97%.
When we compared baseline inhaler costs for participants on entry to the study, against the inhaler costs on completion, we found a significant total annual cost-saving of £18,438.
What does the study tell us?
It tells us that primary care practices were happy to support this research but did not have the time or resources to undertake it during their day-to-day work. To undertake a larger study would require additional resources.
Achieving enough eligible and consenting participants would be difficult. We identified 2,235 eligible individuals but only 3% of this number were successfully recruited. To recruit larger numbers, the study would need to be open in different sites (multi-centred), with many hospitals and primary care practices taking part.
Of those recruited, most participants completed all follow up visits, with very few dropping out or being lost to follow up. It was possible to collect the key data required to measure outcomes, which reassured us that the study protocol design was robust. The study protocol appeared to be safe. There were three deaths during the study, which were independently reviewed and not attributed to study involvement.
The clinical outcomes suggest that inhaled steroids could be stopped in some groups of patients who do not have a history of exacerbating, have lung function >50% and who do not live alone. This hypothesis would need to be tested in a larger study but seems to support the current indications for prescribing inhaled steroids for those who experience exacerbations.
Rationalising medication prescribing, making treatment plans easier and involving patients in inhaler device choice may improve adherence and clinical outcomes. This topic is worthy of further exploration with research studies designed specifically to answer these questions.
It is unlikely that this research will lead to the undertaking of a larger linked study. It would require significant funding and resources to recruit small numbers in many different hospitals and primary care practices. There has also been further research, evidence and guidance developed since the initiation of this study giving practitioners a clearer and consistent message on when they should be using inhaled steroids, including approaches for trialing and stopping inhaled steroids in certain circumstances.REC name
Wales REC 7
REC reference
17/WA/0009
Date of REC Opinion
15 Feb 2017
REC opinion
Further Information Favourable Opinion