Inhaled therapy remains the mainstay of asthma pharmacology, with inhaled steroids (ICS) treating airway inflammation, and both short-acting and long-acting beta2 agonists (SABA and LABA) treating bronchoconstriction (British Thoracic Society (BTS)/Scottish Intercollegiate Guideline Network (SIGN), 2019; Global Initiative for Asthma (GINA), 2018).
While national and international guidelines support the use of ICS and LABA therapy (The National Institute for Health and Care Excellence) (NICE), 2017), the advice given is mostly generic. Yet conversely, generic prescribing should be avoided, and inhaled medication should only be prescribed by the brand name (Capstick et al, 2015; BTS/SIGN, 2019).
The number of ICS/LABA combination inhalers available for the treatment of asthma in the UK has increased to a total of 20 different brands, including generics. These combinations are available in 10 different inhaler devices, which, with the individual doses, represent forty different ways in which the health professional can prescribe inhaled ICS/LABA combination therapy for asthma (Booth, 2020; Electronic Medicines Compendium (EMC), 2020). When combined with inhaled therapy for chronic obstructive pulmonary disease (COPD), and the many individual mono-components and generics, there are currently 119 different ways that health professionals can prescribe inhaled therapy (Right Breathe, 2020).
Nurse prescribing is increasing and is having a greater significance in the healthcare setting. Nurses not only prescribe, but non-prescribing nurses also give advice to prescribers (Cipher et al, 2006). Previous studies looking at habits and beliefs of health professionals have focused on primary and secondary care doctors (Bousquet et al, 2012). There is a need to understand nurses and other health professionals' beliefs about prescribing in respiratory care, and how decisions are made to choose one drug or device over another (Creedon et al, 2015). As nurses have a significant part to play in management of people with long-term conditions, including asthma, understanding how they choose to prescribe ICS/LABA therapy, may help to guide nurse education and training, and subsequently improve disease control for people with asthma.
To gain further understanding of health professionals' habits and beliefs of prescribing ICS/LABA therapy in asthma, a survey was undertaken of primary healthcare professionals. The survey also provided an original opportunity to learn more about nurses prescribing habits and beliefs, which does not appear to have been addressed before, and to compare these habits and beliefs to those of General Practitioner (GPs).
Methodology
Questionnaires were circulated to delegates attending a series of evening educational meetings around asthma and national guidelines. As there is a growing plethora of combination inhalers, including a new mix of generics, for simplicity it was decided to include the four main combinations that were most widely prescribed in the locality, and which had been available for the longest time. These included fluticasone/salmeterol (Seretide®), budesonide/formoterol (Symbicort®), beclometasone/formoterol (Fostair®), and fluticasone/formoterol (Flutiform®). Two choices of Seretide® were given; metered dose inhaler (MDI) and Accuhaler®, as this formulation is the only one of the four at the time that was available in two different inhaler devices.
As this study is focused on asthma, ICS/LABA combinations that are not licensed for asthma were excluded, as were long-acting muscarinic antagonist (LAMA) combinations.
Advice was sought from the local research and development department, and no ethics committee approval was required.
A total of 125 questionnaires were circulated to delegates attending evening educational meetings in the midlands and north of England during 2014 and 2015. At the end of the meeting, delegates were asked to anonymously complete the questionnaire. Delegates were advised that there was an intention to publish the aggregated data. Questionnaires were collated by the study investigator. The educational meetings were sponsored by Napp Pharmaceuticals (promoters of the ICS/LABA combination, Flutiform®), who provided funding for the venue, evening meal, and honoraria for the speaker. The clinical content of the meeting was not influenced by Napp, and was delivered entirely by the speaker/study investigator. No promotional activities were conducted during the meetings, which were conducted in line with the Association of British Pharmaceutical Industry Code of Practice for the Pharmaceutical Industry (The Prescription Medicines Code of Practice Authority (PMPCA), 2016).
Results
From the 125 questionnaires that were circulated, 125 were completed. A total of 20 questionnaires were excluded due to incomplete data. For simplicity, a random selection of 100 of the remaining 105 were analysed. 18 GPs and 82 primary care nurses completed the questionnaires.
Factors influencing prescribing
Delegates were asked to rate, in order of importance from 1-7, the reasons they might base their decision on selecting an asthma inhaler, where one was ranked as the most important and seven the least important. The sum of the score for each response was collated, with higher scores indicating low importance, and lower scores indicating higher importance. To compare GP responses with nurse responses, an average was taken.
Patient preference was cited as the most important reason for choosing an inhaler (mean 3.0, mode 1, range 1-7), with choice of drug being least important (mean 5.6, mode 7, range 1-7). National guidelines were considered more important than local guidelines, with cost and the inhaler device being ranked low in importance.
In comparing GP and nurse responses (Figure 1), there were some considerable differences. GPs ranked local guidelines as being the most important reason for prescribing (mean 2.6), with national guidelines second (mean 3.00), and experience with the product third (mean 3.28).
Nurses ranked patient preference as the most important reason for selecting an inhaler (mean 2.78), with product experience second (mean 3.48). National guidelines were more important than local guidelines, ranked 3rd and 5th respectively. Nurses considered choice of device to be more important than GPs. Both GPs and nurses ranked choice of drug as the least important reason for selecting inhaled combination therapy.
Delegates were asked to record if, as their usual first-line choice, they selected separate ICS and LABA devices, or a combination ICS/LABA device. Of the 95 who specified a preference, 16 (17%) would select separate inhalers and 79 (83%) would select combination. Slightly more nurses (83%, n=67) would select a combination than GPs (78%, n=14).
Age Groups
When asked in which age group separate or combination inhalers were used, health professionals stated that they used separate inhalers for younger patients, and combination inhalers for older patients.
Combinations were more likely to be prescribed for adults and teenagers, whereas separates were more likely to be prescribed for adolescents and paediatrics (Figure 2). In the paediatric group, all 18 (100%) GPs would prescribe separate inhalers and none would prescribe combination. Of nurses, out of 77 who responded, 42 (56%) would prescribe separates, seven (9%) would prescribe combination, and one (1.3%) would prescribe both.
In the adult group, 15 (83%) of GPs would prescribe combinations, and three would prescribe both separate and combination inhalers. Of nurses, two (2.6%) would prescribe separates, 59 (77%) would prescribe combinations and 16 would prescribe both. There were no clear differences between nurse responses and GP responses.
Which brand?
Respondents were asked to state which combinations they used for people with asthma and for people with COPD. Nearly all respondents stated that they used more than one combination, with five stipulating that they used none and would choose separates. A total of 48 respondents used all five combinations listed, with the average being four.
The most common choice of drug overall (asthma and COPD) was Seretide® (n=169, 43%), which was split into metered dose inhaler (22%) and Accuhaler® (21%). Next choice was Symbicort® (n=89, 23%), then Fostair®(n=71, 18%), then Flutiform® (n=62, 16%). The most common choice of device was Symbicort® Turbohaler® (Figure 3).
In asthma, there were no differences in choice between nurses and GPs. However, in COPD, there were differences in combination choice between nurses and GPs, significantly in the off-label prescribing of Seretide® MDI and Flutiform, which were not licensed for COPD. Nurses chose off-label in 23% of cases, whereas GPs chose these in 39%.
What makes an ideal inhaler?
Respondents were asked to state what they felt made an ideal inhaled device for combination therapy (Figure 4). A dose counter was considered the most important aspect of an ideal ICS/LABA combination inhaler by n=70. An MDI/aerosol was felt to be ideal by a greater number of respondents (n=61) than dry powder inhaler (n=51), with choice of drug and number of drugs being chosen by the fewest number (n=36 and n=19).
Treatment regime
Respondents were asked to comment on the advantages and disadvantages of four different types of treatment regimes in asthma. This aspect of the questionnaire was entirely qualitative. The four different methods of treatment were described briefly in the questionnaire, and also discussed during the speaker presentation beforehand, and these were:
- Maintenance and reliever therapy (MART)
- Adjustable maintenance dose (AMD)
- Fixed dose
- Separates.
Maintenance and reliever therapy could be used with formoterol-based combination inhalers, which preclude the need for an additional short-acting B2 agonist ‘reliever’ inhaler, making one inhaler in total.
MART was considered by nurses to be beneficial for concordance and simplicity for the patient. Nurses also stated that cost to the patient in terms of prescription charges, was also an advantage. Nurses felt that this regime worked better for patients. One respondent stated that: ‘patients like the MART regime – they feel it works better.’ Simplicity was felt to be of benefit in this treatment regime. Respondents commented that: ‘patients don't need to understand the difference between preventer and reliever’ and there is ‘reduced confusion about what to use and when’.
There was acknowledgement of the variable nature of asthma, and also on the dangers of people with asthma who rely too heavily on short-acting B2 agonists; ‘good for up down according to symptoms; one inhaler only; good for people who rely on Ventolin’.
Disadvantages expressed by nurses focused on fears of inhaled steroids overuse, and that the patient would not understand how to step down. There was also some concern that the MART method was inflexible and that it was difficult to step down.
GPs said that advantages of MART were that it led to better compliance and was easy for patients to use. One GP commented that, with MART, patients have a better understanding of how to increase their inhaled therapy when they were becoming unwell.
Disadvantages given by GP were the cost and overuse of medication when the patient was well. Concern was expressed that patients might not understand this treatment regime, stating that they may have an ad-hoc approach to treatment, that some patients wouldn't understand it, they could use too much, and they might persist with treatment when symptoms get worse.
Adjustable maintenance dose (AMD) was defined as where the patient increases and decreases their combination inhaler according to their symptoms and/or peak flow. An additional short-acting B2 agonist ‘reliever’ inhaler is also prescribed as required, making two inhalers in total.
Nurses stated that advantages to this method were that the patients could maintain control and that it would be easier for them to step up and step down. The word ‘control’ was often used, both in terms of ‘asthma control’ and keeping patients symptom-free, and in terms of the patient ‘having control’ of their asthma medication and symptoms. Words such as ‘empowerment’ and ‘compliance’ were also used positively.
Overuse, taking too high a dose, and not stepping down, were disadvantages stated by nurses. They also felt that patients would need a great deal of education about this method, and that time to do this was not always available in a 10 minute consultation. Nurses also expressed concern that the dose of LABA either could not be adjusted, or that there was a danger in the patient taking too much LABA.
GPs felt that AMD enabled patients to titrate the dose themselves, and that this would ensure the optimum minimum dose. This would appear to be in contrast with nurses concerns that patients would take too much. GPs stated disadvantages to this method were that it could be too complex for some patients and one GP stated that it was ‘not suitable for all patients’.
Fixed dose combination (FDC) refers to a fixed dose of LABA/ICS combination that is not altered. An additional short-acting B2 agonist ‘reliever’ inhaler is also prescribed as required, making two inhalers in total. Positive attributes from nurses were that this method was simple and less confusing for patients. Nurses commented that FDC ensured the patient stayed on the correct doses and were correctly medicating, that there was no confusion for the patient and it maintained the status quo. This method was also felt to be more suitable for elderly patients, and for those who did not wish to adjust doses themselves.
Disadvantages expressed by nurses included inflexibility, inability to vary doses and that FDC was too prescriptive. Many nurses felt that patients could take more inhaled steroid than needed, and that there was a danger of not stepping-down their therapy.
GPs felt this was a clear and easy to understand way of managing asthma, with GPs stating ‘more people are familiar with this regime’. Lack of flexibility and potential overuse of SABA were disadvantages expressed by GPs.
Separates refers to separate inhalers for LABA, and ICS, and an additional short-acting B2 agonist ‘reliever’ inhaler is also prescribed as required, making three inhalers in total.
Few respondents indicated that separate ICS and LABA inhalers were used. However, some nurses felt the advantages of this method were that it was easy to step up and down. The biggest disadvantage expressed by nurses was that there were ‘too many inhalers’ and that this might lead to reduced adherence. Another disadvantage stated was that patients may take their LABA but not their ICS.
Discussion
Patient preference was ranked the most important reason for selecting an asthma inhaler, both overall, and for nurses, whereas GPs ranked this only as 4th. Nurses also placed more importance on the type of device than GPs. This could be because nurses are, perhaps, more likely to check and optimise inhaler technique, and support joint decision-making with the patient.
Nurses preference for national rather than local guidelines may be explained through the educational content of asthma courses, which rely heavily on national guidelines, and which are attended largely by practice nurses. Local guidelines or formularies compelled by Clinical Commissioning Groups, sometimes have incentives or financial penalties, which may be of important consideration to GP practice partners. Because data were collected in different geographical areas, it was not possible to determine if prescribing decisions were based on or influenced by local guidelines.
The choice of drug was considered to be the least important reason for choosing inhaled combination therapy.
When looking at which combination inhalers health professionals used, there was a direct correlation between the length of time each brand of combination has been available, and the number of health professionals prescribing it. Seretide was the most widely used (licensed 1999), followed by Symbicort (2001), then Fostair (2007) and Flutiform (2012). A likely explanation for this is that HCPs have had more exposure to older combinations and had longer time to prescribe them for more patients. These combinations could be considered to have occupied a ‘first mover advantage’ gaining a competitive advantage and securing a monopoly, if marketed successfully by the pharmaceutical company responsible (Lieberman and Montgomery, 1988).
Nurse and GPs ranked aerosol/MDI slightly higher than DPI (Figure 4). The main reason given for this was that the MDI could be used with a spacer. Some respondents stated that a spacer was better for use in an asthma attack.
One commented that some patients do not like the taste or sensation of a dry powder inhaler, and another respondent said that patients found the feeling that the aerosol of an MDI produced was reassuring. While deposition or impaction of the drug on the oropharynx or back of the throat may appear to be reassuring to the patient, this does not mean that the drug has reached the target organ, ie the lungs.
A common theme throughout the free text comments was the importance of ‘ease of use’ for the patient.
Results of the survey suggest a general acceptance that MART is simpler for patients, and more cost-effective in terms of reduced prescription charges. However, there were concerns that people with asthma may take too much inhaled steroid with the MART approach. This would appear to be in conflict with published evidence, including a systematic review that confirmed previous studies showing that patients take less inhaled steroid with MART and yet have fewer exacerbations, oral steroids or hospital attendances when compared to traditional fixed dose strategies (Kew et al, 2013).
Conclusion
When selecting a combination inhaler, nurses looked toward patient preference, their own experience with the product, and national guidelines to make a decision, whereas GPs preferred to rely on local guidelines. Cost was rated of low importance by both nurses and GPs. Nurses placed greater importance on the device than GPs. Both nurses and GPs placed choice of drug as the lowest ranked consideration when choosing a combination inhaler. This would seem to indicate that nurses and GPs feel there is little or no difference in the drugs that are delivered by the five individual inhalers, despite there being three different inhaled steroids and two different long-acting B2 agonists available for selection within the survey.
When choosing an inhaler device, a dose counter was considered to be the most important consideration. Overall, slightly more health professionals preferred an MDI rather than a DPI, as the MDI could be used with a spacer in an emergency.
Generally, health professionals liked the single inhaler (or MART) and adjustable maintenance therapy approaches, as they felt they were more flexible and gave control back to the patient. Despite these approaches being available for several years, there would appear to be an opportunity for nurses and GPs in primary care to understand more about how these regimes work and their effect on inhaled steroid load. This represents an opportunity for further education of both nurses and GPs. With an increasing number of drugs and devices, clarity is needed to bring sense to a potentially confusing respiratory pharmacological marketplace.
It may now be interesting to compare the responses gathered from this study, with similar responses from people with asthma. Comparing and contrasting any differences between the two sets of data may uncover a need, the solution to which could intimately bring together the thinking of patient and professional.
Key Points
- Nurses consider patient preference as the most important factor when choosing inhaled therapy
- GPs tend to rely on local guidelines, whereas nurses rely more on national guidelines
- Dose counter was considered the most important characteristic of an inhaler device
- Combination inhalers were considered better than separate inhalers
- Although there was an understanding of the workings of maintenance and reliever therapy (MART), there was a clear need for better understanding of this important therapeutic intervention
CPD reflective questions
- Thinking about your last five patients with asthma, how have you made decisions about changing their inhaled therapy?
- Reflecting on your last five patients with asthma, how much involvement did they have in the choice of their inhaler and their device?
- How closely are your beliefs about inhaled therapy aligned with those of your patients and colleagues?
- When choosing inhaled therapy, is the choice of drug as important as the choice of device?
- What do you consider to be the advantages and disadvantages of ICS/LABA maintenance and reliever therapy (MART)?