The impact of unsupervised and unconsented switch of inhalers in patients with controlled asthma – A targeted literature review

Abstract

Inhaler combination formulations consisting of an inhaled corticosteroid (ICS) (fluticasone propionate) and a long-acting β2 agonist (salmeterol xinafoate) are indicated as maintenance treatments for patients with asthma and/or for selected patients with chronic obstructive pulmonary disease. The emergence of generic equivalents to branded inhalers is expected to offer economic edge/savings; however, some may argue that cost advantages offered by generic inhalers may be offset by worsening outcomes due to improper inhaler use, reduced adherence, and consequently worse disease control. To understand how unsupervised and unconsented switch of dry-powder inhalers and/or metered-dose inhalers affects clinical and humanistic outcomes in asthma, comprehensive searches of Embase and MEDLINE were conducted to identify research articles published in the English language since 2011. Patients with asthma of any age who underwent an unsupervised and unconsented switch from an ICS/long-acting β2 agonist to another (brand-to-generic or brand-to-brand) for non-medical reasons were the target of this research. Relevant outcomes included asthma control, medication adherence, and healthcare resource utilization. In total, 11 studies were identified for review (ten non-interventional and one post hoc); cohorts ranged from 19 to 42,553 patients. Six studies indicated that unsupervised and unconsented inhaler switch had a negative impact on asthma control; six studies indicated reduced medication adherence post-switching; and five studies reporting healthcare resource utilization showed it was unchanged or increased post-switching. Findings from this targeted review support concerns that unsupervised and unconsented inhaler switch has a largely negative impact on asthma-associated outcomes. Additional studies are warranted to further explore unsupervised and unconsented switch in asthma.

Asthma is a chronic respiratory disease characterized by variable airflow limitations and respiratory symptoms[¹] that affects approximately 7%–18% of the global population.[²] National prevalence rates of asthma vary between countries and in many cases are increasing over time; for example, in Saudi Arabia, the prevalence of asthma in people aged 8–16 years increased from 8% to 23% between 1986 and 1995.[³] In 2013, the overall prevalence of asthma in Saudi Arabia among people over 15 years of age was 4%; rates were highest amongst people over 65 years of age, at approximately 6% for both men and women.[⁴] Evidence from relevant literature indicates that asthma symptoms are often uncontrolled among patients from Saudi Arabia,[⁵] including approximately 64% of adults and 59% of children.[⁶] This suggests that asthmatic patients often are not optimally controlled or receiving appropriate management.[⁵] For example, a patient survey by Tarraf et al. from June 2014 to December 2015 found that 97.1% of people with asthma in Saudi Arabia were prescribed treatment; however, only 22.9% had good medication adherence.[⁷] Low medication adherence is also prevalent among Saudi Arabian patients with chronic obstructive pulmonary disease (COPD); 64.2% of such patients demonstrate low adherence, compared with 11.6% who are highly adherent according to Morisky Medication Adherence Scale criteria.[⁸] A sizeable fraction of patients in the Tarraf et al. study had somewhat controlled (~30%) or uncontrolled (~40%) asthma according to Global Initiative for Asthma criteria, while using the asthma control test (ACT) criteria, over half (~55%) of patients were considered to have uncontrolled asthma.[⁷] Another survey conducted in Saudi Arabia found that 64% of people with asthma were uncontrolled according to ACT criteria.[⁹]

Inhaler combination formulations consisting of an inhaled corticosteroid (ICS) (fluticasone propionate, ICS) and a long-acting β2 agonist (salmeterol xinafoate) are indicated in the regular treatment of asthma and/or for selected patients with COPD.[¹⁰] The provision of a bioequivalent ICS or ICS/long-acting β2 agonist combination, instead of that which has been prescribed to a patient, without the consent of the patient or a supervising physician, can be considered as unsupervised and unconsented switching. This can include brand-to-brand or brand-to-generic exchange and has been implicated in low medication adherence and reduced disease control.[¹¹] The potential clinical impact and economic savings associated with inhaler unsupervised and unconsented switch, and the consequences of switching on patients with controlled asthma, have recently become a topic for debate.[¹¹] While branded and generic versions of a given inhaled medication must use bioequivalent, chemically identical compounds,[^12,13] there is between-brand variation in the inhaler devices used; this may occur within the same device type (e.g., two different dry powder inhalers), or between inhaler types (e.g., dry powder vs. pressurized metered-dose inhaler). Thus, between-brand differences in therapeutic effect may be observed for the same medicinal compound, driven by variations in the dose and particle size delivered to the lungs, or by the patient’s ability and willingness to use the inhaler.[¹²] Switching between branded medications can be driven by efficacy and/or ease of use, whereas switching from branded to generic medications is usually considered to be motivated by cost-saving considerations.[¹¹] The latter approach may be considered a positive step due to regulatory alignment ensuring equivalent efficacy between drugs and reduced cost burden. However, the unsupervised and unconsented switching of inhalers may lead to improper device use and reduced treatment adherence, ultimately offsetting cost savings due to worsening asthma control and/or increased visits to medical emergency departments.[^14,15] In Saudi Arabia, patients can have access to multiple health centers that each might prescribe a different inhaler, which may be additionally complicated by unsupervised and unconsented switch practices. Maintaining control of asthma and COPD, conditions that can often present with comorbidities,[^16,17] can be challenging for patients and may further be impacted by unsupervised and unconsented inhaler switching.

This targeted literature review was conducted to explore the impact of inhaler unsupervised and unconsented switch on asthma control, healthcare resource utilization, medication adherence, and asthma-related quality of life, and describes the potential clinical and economic impact of unsupervised and unconsented inhaler switch for patients with controlled asthma.

Methods

Search strategy

The targeted literature search was performed within Embase and MEDLINE simultaneously using the ProQuest platform and pre-defined search strings. The search was performed on January 4, 2022.

Study eligibility criteria

Study inclusion and exclusion criteria were developed to guide article selection based on the aims of the review, including articles published in 2011 or later [Table 1]. Studies with patients with asthma of any age who had undergone an unsupervised and unconsented switch from a branded ICS to another ICS for nonmedical reasons, or from an ICS/long-acting β2 agonist to another such combination for nonmedical reasons, were included in the study cohort. Studies involving patients with asthma who had switched inhalers for medical reasons were excluded. Included outcomes were asthma control (direct assessment or healthcare resource utilization changes), medication adherence, patient brand preference, and asthma-related quality of life.

Table 1: Inclusion and exclusion criteria

Data collection process

Results from the literature searches were downloaded and organized into a single database within Microsoft Excel. Citations were screened in a targeted manner for inclusion in the literature review with the assistance of the Colandr tool, which uses machine learning and natural language processing approaches to predict relevant citations. Study inclusion and exclusion were based on the predefined inclusion and exclusion criteria [Table 1]. After relevant publications were identified, data were extracted by a single reviewer, followed by a review from a senior reviewer for quality control purposes. Variables extracted from all studies included study characteristics (e.g., design and data source), patient demographics and clinical characteristics (e.g., age, sex, and asthma treatment), patient-reported outcomes (e.g., asthma-related quality of life), and clinical effectiveness (e.g., asthma control and medication adherence) before and after switching inhalers [Supplementary Table 1]. Data on outcomes of interest are presented descriptively and were summarized as better/neutral/worse or increased/no change/decreased.

Supplementary Table 1: Extraction variables

Results

Six-hundred and sixty-one original research articles published in the English language from 2011 onward were initially identified from the Embase and MEDLINE searches [Supplementary Table 2]. Included studies were peer-reviewed articles and conference abstracts.

Supplementary Table 2: Search strings for Embase/MEDLINE

Study selection

Of the 661 identified research articles, eight studies were included in the review: six of these met the inclusion/exclusion criteria, while two additional studies that were conducted before 2011[^15,18] were included because of their high relevance to the impact of unsupervised and unconsented inhaler switch on asthma control, health-care resource utilization, medication adherence, and asthma-related quality of life [Figure 1 and Table 2]. A further three studies that did not exclusively include unsupervised and unconsented switch patients were also examined.[^20,24,26] Details of the switches in treatment reported in the included articles are explained in Supplementary Table 3. All of the eight studies included in the review and three additional studies examined are published in peer-reviewed journals and are accessible through PubMed. Eight were funded by pharmaceutical companies, either directly (n = 6)[^19,20,23-26] or by unrestricted grants (n = 2).[^15,18] One study was funded by a grant from the Dutch Foundation for Asthma Prevention.[²²] Two studies received no funding.[^11,21]

Table 2: Study details and patient characteristics for the 11 articles included in the targeted review, stratified by type of comparison

Supplementary Table 3: Treatment switches reported in included articles

Figure 1: Identification of studies via Embase/MEDLINE databases - PRISMA flow diagram. *Two of the examined studies were not exclusively unsupervised and unconsented switch, therefore total studies examined, n=11

Study design

Of the eight studies included, all were non-interventional;[^{11,15,18,19,21-23,25}] one additional study was a post hoc investigation of data from a randomized trial in which not every patients’ switch was unsupervised and unconsented.[²⁴] Six studies described patient outcomes before and after inhaler switching,[^{11,15,19,21-23}] while one additional study described this among patients who were not exclusively switched without consent or supervision.[²⁰] Two more studies described patient outcomes compared to those who had not switched inhaler;[^18,25] an additional study describing patients who were not exclusively switched without supervision or consent was examined for this measure.[²⁴] Of these eight studies, only one described patient preference obtained through interviews,[¹⁵] while another supplementary investigation described preference among patients whose inhaler switch had not been solely unsupervised and unconsented.[²⁰] One study compared outcomes before and after switching, as well as patient outcomes compared to those who had not switched, in a population that included patients who had been supervised or had consented to switching[²⁶] [Table 2].

Patient and treatment characteristics

The size of the patient populations studied varied widely, ranging from 19 to 42,553 patients. While some studies included patients with COPD,[^19-21,23] individuals with an asthma diagnosis comprised at least 45% of the overall population in each of these studies. In two of the eight included studies, patients switched to a specific treatment/treatment combination[^11,25] (three additional studies described this among patients who did not exclusively undergo unsupervised and unconsented switch[^20,24,26]), while in two studies the majority of patients switched between the brand and generic versions of a single drug.[^21,22] In the remaining four studies, patients switched to different drugs and/or devices.[^15,18,19,23] Stated reasons for switching inhalers were diverse, including reduced reimbursement, formulary block, cost savings, and lower carbon footprint [Table 2].

Outcomes and synthesis

Asthma control

In total, 7 of the eight studies described asthma control measures,[^{11,15,18,19,21,23,25}] which included exacerbations and management of medication, as well as patient self-reporting using validated instruments (e.g., six-item Asthma Control Questionnaire or another qualitative measure). Three additional studies described asthma control among patients whose inhaler switch was not solely unsupervised and unconsented.[^20,24,26] Six of the seven studies indicated that unsupervised and unconsented inhaler switch was implicated in worse control for a proportion of patients[^{11,15,18,19,23,25}] [Table 3], for example, McCarthy et al. reported that 17.2% of patients required a change of therapy due to worsened asthma control ≤12 weeks following switching,[¹¹] while one study that did not exclusively include unsupervised and unconsented Switch patients by Gilbert et al. found that 62% of patients had not well-controlled asthma ≥3 weeks after switching according to Asthma Control Questionnaire-6 criteria.[²⁰] Doyle et al. similarly reported that while 63% of patients with asthma demonstrated well-controlled disease before unsupervised and unconsented switch, many reported more asthma symptoms following switching.[¹⁵] In contrast, Rhee et al.(who compared retrospective cohort data for patients who had not exclusively switched without supervision or consent during the 12 months before and after index, as well as switched and non-switched cohorts) described that an increased number of patients were free from severe disease exacerbation (58.3% vs. 47.4%) while patients experienced significantly fewer severe acute respiratory events.[²⁶]

Table 3: Studies describing asthma control following switch, stratified by type of comparison

Medication adherence or persistence

Adherence or persistence measures were described by all eight studies[^{11,15,18,19,21-23,25}] and included the duration that patients remained on the switched medication and gaps in treatment; switching to a prior medication; and medication possession ratio. Six of these eight studies indicated that unsupervised and unconsented inhaler switches had a negative impact on medication adherence or persistence[^{15,18,19,22,23,25}] [Table 4]. Björnsdóttir et al. compared observational retrospective population data from 8241 patients with asthma and/or COPD; they reported that 48.6% of patients no longer received any respiratory medication during the 12 months following switching, including 54.0% and 35.7% of patients with asthma and COPD respectively.[²³] Similarly, Doyle et al. found that 42.1% of patients switched to their original medication following unsupervised and unconsented switch.[¹⁵] These data contrast with another study by Bloom et al. where it was reported that following switching 95% of patients with asthma remained adherent to their new inhaler, while the medication possession ratio among switched patients increased significantly from 54.8% to 62.6% (P < 0.001).[²¹] Another study described the impact of not exclusively unsupervised and unconsented inhaler switch on medication adherence and persistence; 15% and 20% of switched versus nonswitched patients exchanged their inhaler prescription within 12 months of switching, demonstrating a neutral effect.[²⁴]

Table 4: Studies describing medication adherence or persistence following unsupervised and unconsented switch, stratified by type of comparison

Healthcare resource utilization

Five of the eight studies described the effect of unsupervised and unconsented inhaler switch on healthcare resource utilization, with measures including the frequencies of consultations with a healthcare professional and hospitalizations.[^{11,18,21,23,25}] Health-care resource utilization was reported to be unchanged[^11,18,21] or increased[^23,25] following switching by the five studies in which it was investigated [Table 5]. One study found that healthcare visits increased by 44.0% among patients with asthma and/or COPD during the 12 months following switching,[²³] while another reported that no more asthma-related hospitalizations occurred during 12 weeks after unsupervised and unconsented switch.[¹¹] Studies comparing matched cohorts of switched and non-switched patients found that patients with asthma without primary health-care visit at switch had significantly more outpatient hospital visits[²⁵] or no significant difference in hospitalization or health-care professional consultation rates between cohorts.[¹⁸]

Table 5: Studies describing healthcare resource utilization impact of unsupervised and unconsented switch, stratified by type of comparison

Quality of life and patient brand preference

The impact of unsupervised and unconsented inhaler switch on patient quality of life and patient brand preference was described by just one of the eight studies[¹⁵] while another described the impact among patients whose inhaler switch had not been exclusively unsupervised and unconsented.[²⁰] Measures included interviews, which were either unstructured or series of specific questions, and written questionnaires such as the Patient Satisfaction and Preference Questionnaire and Obligatory Exercise Questionnaire. The studies described the impact on quality of life as being either neutral[²⁰] or worse[¹⁵] following switching [Table 6]; Gilbert et al. described Patient Satisfaction and Preference Questionnaire scores of 6.2 and 6.0 for patients with asthma and COPD, respectively.[²⁰] The study by Doyle et al. suggested that the majority of patients perceived a worsened doctor-patient relationship and medicine overuse due to a lack of confidence or training with a new inhaler following switching.[¹⁵]

Table 6: Studies describing patient preference following inhaler switch

Economic effects

Finally, only three of the eight studies described the economic impacts of inhalers unsupervised and unconsented switch, either through costs to payers or out-of-pocket costs to patients [Table 7].[^11,19,21] One additional study described economic effects among patients whose inhaler switch was not exclusively unsupervised and unconsented.[²⁶] The single study describing out-of-pocket costs to patients reported an increase following switching,[¹⁹] while costs to payers were reported to be equivalent in another.[²⁶] Bloom et al. predicted potential UK National Health Service cost savings of up to £112 million if all patients with asthma were to switch to a generic or branded bioequivalent device; however, the study did not account for the potential economic impact of switching resulting from the potential cost of patient training with a new device.[²¹] McCarthy et al. similarly described average annual savings of $3127 per patient to relevant healthcare organizations.[¹¹] Gilbert et al. reported that patient out-of-pocket costs increased by 12% and 26% for all respiratory controllers and ICS/long-acting β2 agonist combinations, respectively.[¹⁹]

Table 7: Studies describing the economic effects of inhaler switch, stratified by type of comparison

Discussion

The studies identified by this targeted review indicate that unsupervised and unconsented inhaler switch is generally associated with worse outcomes for patients in terms of reduced asthma control (as measured by Asthma Control Questionnaire, acute medicine use, and exacerbations), greater healthcare resource utilization (i.e., consultations), and lower medication adherence/persistence (as measured by switching back to previous therapy, medication possession ratio, and gaps in treatment).

One of the treatment goals of asthma management is symptom control which includes improved quality of life,[²⁷] and this involves patient perceptions and understanding about their asthma and the prescribed medications.[²⁸] Six of the studies reported that inhaler switch had a negative impact on asthma control for a proportion of patients,[^{11,15,18,19,23,25}] (another described a negative impact among patients who did not exclusively undergo unsupervised and unconsented switch[²⁰]) while only two indicated that unsupervised and unconsented switch had a positive impact.[²¹] However, some aspects of the design of these two studies should be considered when interpreting the results. For instance, in their 2019 study, Bloom et al. did not report information regarding the supervision or consent of patients to a switch of inhaler, and the reasons for switching were not described, although are potentially financially motivated. Furthermore, among patients whose inhaler was switched, there was no clear segregation between those who were medically controlled versus those who were not. The authors suggest that switching inhalers should be unproblematic if implemented correctly; this should include appropriate patient selection and provision of training to patients for use of a new inhaler.[²¹] In another study, published in 2022 by Woodcock et al., patients consented before allocation to the fluticasone furoate/vilanterol randomization arm. Both treatment groups showed improvements in asthma control, with greater control demonstrated in those initiated on fluticasone furoate/vilanterol.[²⁴] The study by Rhee et al. also described a positive impact among patients who did not exclusively undergo unsupervised and unconsented switches.[²⁶]

The impact of unsupervised and unconsented inhaler switch on healthcare resource utilization was explored by several studies. Articles by Björnsdóttir et al. and Bloom et al. were population-wide studies that described healthcare resource utilization before and after inhaler unsupervised and unconsented Switch, based on electronic records from 8241 (asthma, 6142; COPD, 1340) and 23488 (asthma, 18185; COPD, 5303) patients in Iceland and the UK, respectively.[^21,23] The 2022 study by McCarthy et al. was of smaller scope, based on the population of a single multi-center healthcare organization in the United States and featuring 219 patients before and after switching.[¹¹] While the described studies differed in population size, all three described either no change[^11,21] or increased[²³] health-care resource utilization. Results describing healthcare resource utilization for patients who had switched versus those who had not switched inhalers were published by Ekberg-Jansson et al., who reported an increase in healthcare resource utilization among 463 matched patients who had switched,[²⁵] and by Thomas et al., who reported no change in healthcare resource utilization among 824 matched patients who had switched versus those who had not switched.[¹⁸]

One of eight articles describing the impact of unsupervised and unconsented switches on medication adherence or persistence, by Bloom et al. in 2019, reported an improvement, based on significantly increased medication possession ratio.[²¹] This is in contrast to data reported by Engelkes et al. in 2018, which described a significant decrease in medication possession ratio following both brand-to-generic and generic-to-brand unsupervised and unconsented switches.[²²] Both studies were nationwide (the United Kingdom and the Netherlands, respectively) analyses of electronic records over a period of 16 years[²¹] and 9 years.[²²] This difference may be attributable to substantial variation in study characteristics, including cohort population counts (23,488[²¹] and 70,053[²²]). Other articles describing adherence or persistence before and after inhaler switching either reported no change[¹¹] (including one study among patients who were not exclusively switched without consent or supervision[²⁶]) or a reduction[^15,19,23] in adherence or persistence. One article described 42.1%[¹⁵] of patients switching back to their original inhaler following unsupervised and unconsented inhaler switching; another describing the impact of inhaler switching that was not exclusively unsupervised and unconsented reported that 32.1% of patients returned to their original inhaler following switching.[²⁶] One study reported that among patients with a gap in care, 47% filled a prescription emblematic of potential disease exacerbation;[¹⁹] these data align with another study, not included in this review, which indicated that trends of increased use of the short-acting β2 agonist albuterol could suggest lower adherence to regular controller therapy.[²⁹] Articles reporting analyses comparing matched cohorts of patients who did or did not switch inhaler displayed a similar trend; for example, in 2022, Woodcock et al. reported that among patients who switched or did not switch, 15% and 20% respectively underwent a subsequent inhaler switch within a year. The authors concluded that there was no significant difference in adherence.[²⁴] In contrast, another study reported that 33.1% of patients who switched inhaler subsequently changed device in the year following, compared to 22.2% of patients who had not switched.[¹⁸] Variation in findings for these studies could be attributed to evolving common prescribing practices in the United Kingdom; while both were retrospective analyses, the periods during which the data were recorded were 1990–2004, and 2012–2016, for Thomas et al. and Woodcock et al. respectively.[^18,24] It is also important to highlight that for Woodcock et al. a proportion of patients were supervised during inhaler switch and received training in the use of their new devices,[²⁴] which would likely have impacted results.

In a study describing patient preferences and quality of life, patients expressed dissatisfaction with the change made without their consent.[¹⁵] The Gilbert et al. study described the impact of inhaler switch, that was not exclusively unsupervised and unconsented, on quality of life; patients reported general satisfaction with the timing of medication effects, treatment effectiveness, and treatment administration frequency.[²⁰] In the only patient interview study included in this review, several patients did not realize the medication switch until arriving home from the pharmacy; in some cases, patients returned to be trained on the new device.[¹⁵] While this was a small study, it is important to note that concerns about patients having adequate awareness of switching and training are based on real-life examples of inadequate communication with patients and support similar findings from European studies.[^30,31] Limited evidence was identified describing the effects of unsupervised and unconsented switches on patient costs; out-of-pocket costs increased in the single study reporting this outcome.[¹⁹] In the same study, 18-63% of patients who experienced a gap were without an acute medication, and 23% did not switch to a new controller medication within 1 year of the formulary block. These findings are consistent with physicians’ beliefs that inhalers are not interchangeable and that pharmacists should not perform a substitution without consulting with the physician.[^32,33] These perceptions may endure until processes for establishing bioequivalence for generic inhalation drugs are unified and deemed sufficient by physicians and other healthcare decision-makers.[³⁴]

The findings of this targeted review are consistent with a similar article by Björnsdóttir et al., which summarized direct (pharmaceutical performance, inhalation technique, adherence, and asthma control) and indirect (healthcare resource consumption and costs) effects of unsupervised and unconsented inhaler switch based on a review of literature published between 2001 and 2011 (English language listed on MEDLINE).[³⁵] The authors concluded that arguments for and against unsupervised and unconsented switches should be considered carefully, stating that greater investment in improving medication adherence could lead to greater cost savings when considering the potential decrease in demand for health-care services; in contrast, savings made by brand-to-generic switching might be outweighed by losses due to decreased asthma control and increased health-care consumption.[³⁵]

A notable limitation of our study is the relatively low number of articles that we identified, notably describing the economic impacts of unsupervised and unconsented switches, whether for patients or healthcare organizations, and the impact it has on patient inhaler preference. This limitation reflects the relative paucity of the published literature investigating the impact of unsupervised and unconsented inhaler switch on these outcomes in asthma populations. It is also important to note that none of the identified studies compiled data from patients from Saudi Arabia; thus, there is a clear need for a study of the impact of unsupervised and unconsented switches in this setting. Several articles reviewed here did not exclusively describe studies with patients whose inhaler switch was unsupervised and unconsented, thus their evidential value to help us address the research question is limited. Eight of the 11 studies evaluated were funded by pharmaceutical companies, with the level of company involvement ranging from the provision of unrestricted grants to involvement in the study design, data collection, data analysis, and authorship of the published articles.[^{15,19,20,23-27}] Although we note the risk of industry-sponsored bias, in the case of these studies the impact of sponsorship bias was judged to be minimal.

Conclusions

In general, the findings presented here support the perspectives of multiple previous reviews that indicate that negative outcomes of unsupervised and unconsented inhaler switches are likely to offset the potential financial benefits to health-care systems.[^14,35] Patient inexperience with a new device can lead to poor inhalation technique and unintentional reduction in medication adherence.[¹²] Patients who receive a new inhaler may be opposed to, or concerned about, the switch,[³⁶] which might have a negative impact on adherence. Moreover, patients switching inhalers should be carefully guided in clinical practice, as a lack of proper communication between physicians and patients may lead to treatment failure.[³⁷] Current asthma treatment guidelines suggest that patients should be trained in the use of any inhaler; in the unsupervised and unconsented switch scenario, this is difficult to provide.[¹⁴] It is also important to note that only limited evidence was identified here describing the impact of unsupervised and unconsented inhaler switch on out-of-pocket costs to patients; however, these reportedly increased in the single study investigating this outcome identified during this literature review.[¹⁹] It is worth noting that a study of children with asthma found that the group with the highest out-of-pocket costs also had lower adjusted medication use and greater incidence of asthma-related hospitalization than the group with the lowest out-of-pocket costs.[³⁸] In summary, the evidence presented here largely concurs with concerns raised previously regarding medication adherence, asthma control, and health-care resource utilization due to inhaler unsupervised and unconsented switches. We believe that additional study in this area is warranted.

Author contributions

AA, MA, WA, and MHS were involved in study design, data acquisition, and data analysis.

Financial support and sponsorship

This literature review was funded by GSK.

Conflicts of interest

AA declares he is a deputy Editor in Chief at the journal Annals of Thoracic Medicine. MA declares no conflicts of interest. WA declares no conflicts of interest. MHS declares he is a GSK employee and holds shares in GSK.

Figure

Acknowledgments

Medical writing support, under direction of the authors, was provided by Christian Jones, PhD (Ashfield MedComms, an Inizio company, United Kingdom) and was funded by GSK.

Trademarks are owned by or licensed to their respective owners (the GSK group of companies [ELLIPTA] or QualityMetric incorporated [ACT]).