Asthma (in adults) - corticosteroids: Appraisal consultation document
NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE
Appraisal Consultation Document
Corticosteroids for the treatment of chronic asthma in adults and children aged 12 years and over
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The Department of Health and the Welsh Assembly Government have asked the National Institute for Health and Clinical Excellence (NICE or the Institute) to conduct an appraisal of corticosteroids for the treatment of chronic asthma in adults and children aged 12 years and over and provide guidance on their use to the NHS in England and Wales. The Appraisal Committee has had its first meeting to consider both the evidence submitted and the views put forward by the representatives nominated for this appraisal by professional organisations and patient/carer and service user organisations. The Committee has developed preliminary recommendations on the use of corticosteroids for the treatment of chronic asthma in adults and children aged 12 years and over. This document has been prepared for consultation with the formal consultees. It summarises the evidence and views that have been considered and sets out the preliminary recommendations developed by the Committee. The Institute is now inviting comments from the formal consultees in the appraisal process (the consultees for this appraisal are listed on the NICE website, www.nice.org.uk). Note that this document does not constitute the Institute's formal guidance on these technologies.The recommendations made in section 1 are preliminary and may change after consultation. The process the Institute will follow after the consultation period is summarised below. For further details, see the ?Guide to the technology appraisal process? (this document is available on the Institute?s website, www.nice.org.uk).
The key dates for this appraisal are: Details of membership of the Appraisal Committee are given in appendix A, and a list of the sources of evidence used in the preparation of this document is given in appendix B. |
| Note that this document does not constitute the Institute's formal guidance on this technology. The recommendations made in Section 1 are preliminary and may change after consultation. |
| 1 | Appraisal Committee's preliminary recommendations |
| This guidance should be read in conjunction with ?British Guideline on the Management of Asthma?, 2005 (British Thoracic Society [BTS]/Scottish Intercollegiate Guidelines Network [SIGN]) | |
| 1.1 | For adults and children aged 12 years and over with chronic asthma for whom treatment with low-dose inhaled corticosteroids (ICSs) is considered appropriate (step 2 of the BTS/SIGN guidelines), the least costly product that is suitable for the person is recommended. |
| 1.2 | For people in whom treatment with ICSs and long-acting beta-2 agonists (LABAs) is considered appropriate (step 3 of the BTS/SIGN guidelines), the use of a combination device is recommended as an option. The decision about whether to use a combination device or the two agents in separate devices should be made on an individual basis, taking into consideration the likelihood of treatment adherence as well as individual preferences. If both options are considered equally appropriate then the least costly product or combination of products that is suitable for the person is recommended. |
| 1.3 | If treatment with high-dose ICSs is considered appropriate (step 4 of the BTS/SIGN guidelines), the least costly product that is suitable for the person is recommended. |
| 1.4 |
Whenever possible, taking into account sections 1.1 to 1.3, the use of a press-and-breathe pressurised metered-dose inhaler (pMDI) and a suitable spacer is recommended in the first instance. If it can be demonstrated that the person is not able to use a pMDI and spacer effectively, or if this approach is not appropriate for the agent chosen, then alternative devices should be considered.
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| 2 | Clinical need and practice |
| 2.1 | Asthma is a chronic disorder of the airways caused primarily by inflammatory processes and constriction of the smooth muscle in airway walls (bronchoconstriction). It is characterised by airflow obstruction and increased responsiveness of the airways to various stimuli. Symptoms include recurring episodes of wheezing, breathlessness, chest tightness and coughing. Typical asthma symptoms tend to be variable, intermittent, worse at night and provoked by triggers. Asthma is commonly triggered by viral respiratory infections, exercise, smoke, cold, and allergens such as pollen, mould, animal fur and the house dust mite. |
| 2.2 | Asthma is diagnosed on the basis of symptoms and objective tests of lung function (such as peak expiratory flow rate [PEFR] and forced expiratory volume in the first second [FEV 1]) and percentage predicted FEV 1 (calculated as a percentage of the predicted FEV 1 for a person of the same height, sex and age without a diagnosis of asthma). Variability of PEFR and FEV 1, either spontaneously over time or in response to therapy, is a characteristic feature of asthma. The severity of asthma is usually judged according to the amount of medication required to manage the symptoms and is based on the British Thoracic Society (BTS)/Scottish Intercollegiate Guidelines Network (SIGN) guidelines. |
| 2.3 | It is estimated that there are 5.2 million people with asthma in the UK, of whom approximately 2.9 million are women and girls and 2.3 million are men and boys. This includes 0.7 million people older than 65 years and 0.6 million teenagers. The Health Survey for England (2001) estimated the lifetime prevalence of diagnosed asthma to be 16% in women and 13% in men. The 1998 figures from the General Practice Research Database, which sampled 211 general practices in England and Wales, estimated the age-standardised prevalence of treated asthma to be 7% in men and 8% in women. |
| 2.4 | Asthma usually develops in childhood but may start at any age. There is no cure for asthma, although people may experience long periods of remission. Mortality from asthma is rare, with 1266 asthma-related deaths reported in 2004. |
| 2.5 | Poorly controlled asthma can have a significant impact on the quality of life of the affected person and their family. However, there may be variation in an individual?s perception of the symptoms and how he or she adapts to the condition over time. Clinical measures such as lung function may not correlate with an individual?s quality of life, but if asthma is well controlled, near-maximal scores on quality of life instruments can be achieved. |
| 2.6 | Asthma management aims to control symptoms (including nocturnal symptoms and exercise-induced asthma), prevent exacerbations and achieve the best possible lung function, with minimal side effects of treatment. BTS/SI GN guidelines recommend a stepwise approach to treatment. Treatment can be stepped up as necessary and stepped down when control is good. |
| 2.7 | Mild intermittent asthma ( step 1) is treated with inhaled short-acting beta-2 agonists (SABAs), as required. The introduction of regular preventer therapy with inhaled corticosteroids (ICSs; step 2) should be considered when a person has had exacerbations of asthma in the last 2 years, is using inhaled SABAs three times a week or more, is symptomatic three times a week or more, or is waking at night once a week because of asthma. Add-on therapy ( step 3) involves the introduction of an additional therapy, the first choice of which is an inhaled long-acting beta-2 agonist (LABA). Alternatives include orally administered leukotriene receptor antagonists, theophyllines and slow-release beta-2 agonist tablets, or increasing the dose of the ICS. At step 4, further interventions may be considered if control remains inadequate on a dose of ICS that is equivalent to 800 micrograms of beclometasone dipropionate in combination with a LABA (or following an unsuccessful trial of a LABA). Options include increasing the dose of the ICS to 2000 micrograms beclometasone dipropionate equivalent per day or adding a leukotriene antagonist, a theophylline or a slow-release beta-2 agonist tablet. At s tep 5, continuous or frequent courses of oral corticosteroids are introduced. The majority of people with asthma are treated at steps 1 and 2. |
| 2.8 | Asthma exacerbations (or asthma attacks) are acute episodes of a progressive increase in shortness of breath, cough, wheezing or chest tightness, or a combination of these symptoms, usually triggered by a variety of stimuli , most commonly a viral respiratory infection. They lead to the consumption of additional medications or to patient-initiated healthcare consultations, often in expensive healthcare settings such as accident and emergency departments. Severe exacerbations can be life threatening. Most exacerbations can be treated with high doses of inhaled SABAs although sometimes a short course of oral corticosteroids is also needed. |
| 3 | The technologies |
| 3.1 | Five corticosteroids are available as inhaled formulations for the treatment of asthma: beclometasone dipropionate, budesonide, fluticasone propionate, mometasone furoate and ciclesonide. Two of the ICSs are available in combination with a LABA in a single inhaler: fluticasone propionate in combination with salmeterol, and budesonide in combination with formoterol fumarate. |
| 3.2 | ICSs are available in a variety of devices. These are broadly of two types - pressurised metered-dose inhalers (pMDIs), in which the drug is suspended in either a chlorofluorocarbon (CFC) or hydrofluoroalkane (HFA) propellant, and dry powder inhalers (DPIs), in which there is no liquid propellant. CFC-containing products will be phased out in the future. Many people have difficulty using pMDIs due to the problem of coordinating device actuation and inhalation. This can be overcome to some extent by using a device called a spacer to improve airway deposition and reduce oropharyngeal deposition, or by using ?breath-actuated? pMDI inhalers. DPIs deliver micronised drug, sometimes with a carrier powder, using the individual?s own inspiratory flow to create the finely dispersed powder. Both breath-actuated pMDIs and DPIs can be used to overcome the problem of actuation?inhalation coordination associated with pMDIs, but cannot be used in conjunction with spacer devices. |
| 3.3 | Beclometasone dipropionate, budesonide and fluticasone propionate are available as pMDIs and DPIs. Ciclesonide is available as a pMDI only and mometasone furoate is available as a DPI only. The fluticasone propionate/salmeterol combination inhaler is available both as a pMDI and as a DPI, and the budesonide/formoterol fumarate combination inhaler is currently available as a DPI only. |
| 3.4 | The side effects of ICSs may be local (following deposition in the upper airways) or systemic (following absorption into the bloodstream). Local adverse effects include dysphonia, oropharyngeal candidiasis, cough, throat irritation and reflex bronchospasm. Systemic adverse effects include suppression of the hypothalamic-pituitary-adrenal axis, osteoporosis, skin thinning and easy bruising, cataract formation and glaucoma, and growth retardation in children and adolescents. |
| 3.5 | Each ICS is available in a variety of devices and strengths. In general, the DPIs are the most expensive and the CFC-containing products are the cheapest. Breath-actuated aerosol metered-dose inhalers are more expensive than those that are not breath actuated. The CFC-free devices that contain a HFA propellant are more expensive than CFC-containing ones. Costs may vary in different settings because of negotiated procurement discounts. |
| 4 | Evidence and interpretation |
| The Appraisal Committee (appendix A) considered evidence from a number of sources (appendix B). | |
| 4.1 | Clinical effectiveness |
| 4.1.1 | There is a large body of evidence for the use of ICSs in asthma, with studies of various methodologies reported in the literature as well as unpublished studies submitted by manufacturers. The study populations are often hospital based and the inclusion and exclusion criteria frequently make them unrepresentative of the general population of people with asthma. The participants have varying severities of asthma and degrees of symptom control. The drugs are used in different doses, delivered by various devices, and they are compared with other drugs, devices, doses and/or placebo. The trials are generally of a short duration (a few months to a year). A variety of outcomes are measured including changes in lung function such as FEV 1 and PEFR, changes in asthma symptoms or the avoidance of exacerbations, and the use of short-acting bronchodilators or other medications. It is often uncertain how these outcomes relate to quality of life. |
| 4.1.2 |
The Assessment Group identified five questions relevant to the appraisal of these drugs and conducted a systematic review in order to address them. The questions were as follows.
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| 4.1.3 | A total of 22 randomised controlled trials (RCTs) compared ICSs at low doses. All ICSs were compared with fluticasone propionate and budesonide but there were no pairwise comparisons between beclometasone dipropionate, mometasone furoate and ciclesonide. There were fewer studies for the newer drugs (mometasone furoate and ciclesonide - three studies each) compared with the other drugs, which have been available for longer. The Assessment Group concluded that all the ICSs were associated with favourable changes from baseline to endpoint across efficacy and safety outcomes. However, in pairwise comparisons, there were few statistically significant differences between them, and thus it was concluded that there was little evidence to reject the hypothesis that there is no difference in clinical effectiveness between them. |
| 4.1.4 | A total of 24 RCTs compared ICSs at high doses. Ciclesonide was only compared with fluticasone propionate, and mometasone furoate was compared only with budesonide and fluticasone propionate. There were pairwise comparisons for all other drugs with more evidence for the older ICSs. For one comparison of HFA-beclometasone dipropionate the equivalent ratio to HFA-fluticasone propionate was assumed to be 1:1 rather than 1:2. The Assessment Group concluded that all the ICSs were associated with favourable changes from baseline to endpoint across efficacy and safety outcomes. However, in pairwise comparisons, there were few statistically significant differences between them, and thus it was considered that there was little evidence to reject the hypothesis that there is no difference in clinical effectiveness between them. |
| 4.1.5 | Six RCTs compared combination inhalers including a corticosteroid and a LABA with an inhaler containing the same corticosteroid alone at a higher dose, and four compared a corticosteroid/LABA combination with an inhaler containing a different corticosteroid at a higher dose equivalent. Five studies compared the fluticasone propionate/salmeterol combination and five compared the budesonide/formoterol fumarate combination with a higher dose equivalent ICS alone. There were no comparisons of the combined inhalers with beclometasone dipropionate, mometasone furoate or ciclesonide alone. Only trials in which the LABA and ICS were delivered in a single combined inhaler were considered. The Assessment Group found that generally, the addition of a LABA was statistically significantly superior to increasing the dose of ICS across a range of outcomes related to lung function, symptoms, rescue medication use and, to a lesser extent, exacerbations. |
| 4.1.6 | Nine RCTs compared adding a LABA in a combined inhaler to the same dose of ICS alone. Six of these compared the fluticasone propionate/salmeterol combination with fluticasone propionate alone, and three of these were comparisons of the budesonide/formoterol fumarate combination with budesonide alone. The dose of ICS used in the studies varied. There were statistically significant improvements in lung function, asthma symptoms and rescue medication use favouring the combined treatment. The benefit in terms of frequency of exacerbation was not so marked, and there were no significant differences in adverse effects. |
| 4.1.7 | Six RCTs compared an ICS and LABA in a combination inhaler with the two drugs delivered in separate inhalers. The two available combinations (fluticasone propionate/salmeterol and budesonide/formoterol fumarate) were compared with their own components (three and two studies, respectively), and one study compared the fluticasone propionate/salmeterol combination inhaler with budesonide and formoterol fumarate as individual components. No comparisons were made with any other ICS/LABA combination. Because many of these studies used a double-blind double-dummy design ? the patients taking a combination inhaler also received a placebo dummy ? these studies would not be expected to capture fully any benefits of improved treatment adherence with a combined inhaler. There were very few statistically significant differences between the treatments across various efficacy outcomes, and for some outcomes (for example, lung function) non-inferiority was demonstrated. Meta-analysis revealed no statistically significant differences in adverse events. |
| 4.1.8 | Three RCTs compared the two available combination inhalers in their dry powder form (DPIs) and all were in the low-to-medium range of the ICS dose. The outcomes in terms of lung function, asthma symptoms and exacerbations were mixed and conflicting. Meta-analysis found no statistically significant differences in rates of adverse events. |
| 4.1.9 | Seven submissions were received from manufacturers. Four of these concentrated on the delivery device, which was either a DPI with improved characteristics or contained a non-CFC propellant with improved drug-delivery properties. One submission concentrated on an ICS alone and two concentrated on the LABA/ICS combination in a single inhaler. In general, the submissions concerned the products of the manufacturer and no attempt was made to systematically compare all products available on the market. |
| 4.1.10 | Two clinical specialists and one patient expert attended the Appraisal Committee meeting. They confirmed the conclusions of the assessment report and stressed the need for the choice to individualise patients? treatment with access to a wide range of delivery devices. They provided insight into the importance of the type of device in adherence and overall clinical effectiveness of asthma treatment. |
| 4.1.11 | In summary, the Assessment Group concluded that, when comparing the different ICSs, either at low or high doses, there was little conclusive evidence of equivalence and more often there was inconclusive evidence concerning differential effectiveness. It also concluded that adding a LABA is more effective than continuing on the same or an increased dose of ICS. When considering simultaneous treatment with a LABA and an ICS, the Assessment Group concluded that there was no difference in effectiveness when these were administered in a combined inhaler as opposed to separate inhalers and that the two combination inhalers currently on the market were equally effective. |
| 4.2 | Cost effectiveness |
| 4.2.1 | The Assessment Group conducted a systematic review of published economic evaluations of asthma and identified 15 studies. Four studies were analysed from the UK NHS perspective but only one calculated an incremental cost per quality-adjusted life year (QALY). This analysis produced incremental cost-effectiveness ratios (ICERs) of £4,800 to £18,300 per QALY gained for fluticasone propionate/salmeterol compared with fluticasone propionate alone at various dose levels. However, the analysis pooled effectiveness and resource use data from patients in 44 countries and, for this reason, the Assessment Group concluded that the generalisability of these results to the UK setting may be limited. |
| 4.2.2 | Seven submissions were produced by six manufacturers. There was no submission for mometasone furoate. None of the submissions compared all five available ICSs in any form of analysis. All manufacturers produced a cost-minimisation analysis for the ICS products. Four submissions focused on either the device or the propellant associated with the ICS and one on the ICS itself. Two submissions produced a cost-effectiveness analysis for the combination inhalers from a product-specific perspective. |
| 4.2.3 | The Assessment Group addressed the economic evaluation of the five research questions addressed in the effectiveness section (see section 4.1.2). Two of the questions refer to the comparison of ICSs as monotherapy at low and high doses and three to the use of combined therapy (adding a LABA to ICS treatment compared with increasing the dose of ICS; treatment with separate inhalers compared with a combined inhaler; and comparing the available combination inhalers). If there was a lack of consistent evidence of differential clinical effectiveness, a cost-minimisation approach was used. If there was relatively consistent evidence showing differential effectiveness, a cost-consequence approach was adopted. |
| 4.2.4 | To generate a single cost figure for each ICS, a mean annual per-patient cost was calculated. This mean could be unweighted or weighted according to current (2005) market share. As any particular target daily dosage can be achieved in a number of ways given the multiplicity of inhaler strengths available on the market, it was assumed that a dosage would be achieved in a fixed manner using higher strength inhalers to achieve higher total dosages. It was also assumed that fluticasone propionate, HFA-propelled beclometasone dipropionate, mometasone furoate and ciclesonide required half the dose to achieve equivalence with beclometasone inhalers and budesonide. In addition to the mean annual per-patient cost being calculated for all currently available products, it was also calculated with CFC-containing products excluded, because it is anticipated that these will soon be phased out. Because there are a limited number of products for the combined inhalers, the mean cost was calculated for each separate product. In general, the DPIs are more expensive than other device types. The cheapest products are pMDIs that contain CFCs and, with their withdrawal, the overall cost of these ICSs will increase. The weighted averages conceal a very wide variation in the cost of individual preparations for each drug. While the most expensive inhalers for any ICS have similar costs there is a wide variation in cost when considering the cheapest available inhaler. |
| 4.2.5 | At the lower end of the low-dose range (400 micrograms beclometasone dipropionate equivalent per day), the cheapest ICS is beclometasone dipropionate with the weighted mean cost being £62/year and the unweighted mean being £65/year. Excluding CFC-containing products increases the cost but beclometasone dipropionate remains the cheapest ICS (unweighted mean £79/year, weighted mean £90/year). Excluding CFC-containing products has no effect on the mean costs of fluticasone propionate, mometasone furoate or ciclesonide because these are available only as CFC-free products. At the upper end of the low-dose range (800 micrograms beclometasone dipropionate equivalent per day), beclometasone dipropionate is the cheapest product costing £130/year (unweighted mean) and £157/year (weighted mean). When CFC-containing products are excluded, fluticasone propionate becomes the cheapest option if a weighted mean is considered. |
| 4.2.6 | In the high-dose range (800?2000 micrograms beclometasone dipropionate equivalent per day), only four ICSs were compared ? ciclesonide is not licensed for use at an equivalent dose. The cheapest option is beclometasone dipropionate costing £198/year (unweighted mean) and £260/year (weighted mean). When CFC-containing products are excluded, fluticasone propionate is the cheapest ICS using the weighted mean, costing £385/year. This is because cheaper CFC-containing beclometasone dipropionate products currently occupy a relatively larger market share. |
| 4.2.7 | A cost-consequence analysis was conducted because the review of clinical effectiveness found that the ICS/LABA combination therapy was more effective than ICS monotherapy using an increased dose of ICS when equivalent doses of ICS are used. At the low end of the dose range of ICS, the annual cost of the fluticasone propionate/salmeterol inhaler is £92 more than fluticasone propionate alone at a higher dose. However, at the higher end of the dose range, the cost of the combination is £35 less than the ICS alone at a higher dose. When comparing the fluticasone propionate/salmeterol combination with budesonide alone at a higher dose, the combination treatment ranges from £94 cheaper to £109 more expensive depending on the budesonide preparation chosen. The budesonide/formoterol fumarate combination varies from being £163 cheaper to £66 more expensive than a higher dose of either fluticasone propionate or budesonide alone. No comparisons were made between the combined inhalers and other ICSs as monotherapy. The cost-consequence analysis above omits any potential cost savings that may result from avoidance of exacerbations as well as any potential quality-of-life gains associated with better asthma symptom control. |
| 4.2.8 | When the cost of taking a combination inhaler is compared with taking the components separately, the combination product is almost always cheaper than taking the same drugs in separate inhalers. For the budesonide/formoterol fumarate combination, annual savings vary from £36 to £227 depending on the daily dose of ICS and the preparation of the LABA used. For the fluticasone propionate/salmeterol combination the annual savings varied from £85 to £298 using one device (Accuhaler). Only at a very high dose and using another device (Evohaler), the separate inhalers can be the cheaper option, saving £19. |
| 4.2.9 | At the lower dose level (400 micrograms budesonide and 200 micrograms fluticasone propionate), the cheapest combination inhaler is the fluticasone propionate/salmeterol aerosol pMDI, which costs £219/year and is only £12 cheaper than the. budesonide/formoterol fumarate DPI. At the higher dose level (800 micrograms budesonide and 500 micrograms fluticasone propionate), the fluticasone propionate/salmeterol DPI and pMDI are the cheapest at £446/year, which is £16 cheaper than the budesonide/formoterol fumarate DPI. In summary, there is no combination inhaler that is cheapest in all circumstances, and the difference in cost of the cheapest options is minimal. |
| 4.3 | Consideration of the evidence |
| 4.3.1 | The Appraisal Committee reviewed the data available on the clinical and cost effectiveness of ICSs, having considered evidence on the nature of the condition and the value placed on the benefits of ICSs by people with asthma, those who represent them, and clinical specialists. The Committee also considered the existing NICE guidance ?Inhaler devices for routine treatment of chronic asthma in older children (aged 5 -15 years)?, NICE technology appraisal guidance 38. The Committee was also mindful of the BTS/SIGN guidelines on the management of asthma, and of the need to take into account the effective use of NHS resources. |
| 4.3.2 | The Committee considered the evidence on the clinical effectiveness of ICSs and their use within the context of the BTS/SIGN guidelines on the management of asthma. Clinical specialists were in agreement with the dose-equivalent estimates for the effectiveness of CFC preparations of ICS, as presented in the BTS guidelines, but noted that the evidence base for determining the dose equivalence of mometasone furoate and ciclesonide relative to other ICSs was smaller. The specialists also stated that the Qvar brand of HFA-beclometasone dipropionate delivers smaller particles of ICS, which leads to improved lung deposition. Therefore, it may be given at lower doses than beclometasone dipropionate delivered using a CFC propellant to achieve an equivalent effect. The Committee was also aware that CFC devices will be phased out in the near future in accordance with the Montreal Protocol. |
| 4.3.3 | The Committee understood the importance of the use of an ICS in the context of a pathway of care that involves providing people with adequate information regarding their condition, involving them in the management of their asthma with the use of a personal action plan, training them in the effective use of the delivery device, and regular reviews of the effectiveness of their treatment. |
| 4.3.4 | The Committee first considered the RCT evidence on the clinical effectiveness of ICSs at doses equivalent to beclometasone dipropionate up to 800 micrograms per day. The Committee heard from clinical specialists that the RCTs recruited a selected group of individuals with better compliance with treatment and inhaler technique than is generally seen in clinical practice. The Committee heard from the specialists that, although there is little evidence of statistically significant differences in the clinical effectiveness of ICSs from the RCTs, in clinical practice some people respond to some agents/inhaler systems better than others. They stated that at low doses of inhaled steroids (below the beclometasone dipropionate equivalent of 800 micrograms), few people experience local or systemic adverse effects. However, they added that in a small minority of people who experience local side effects (even at low doses) the use of pro-drugs, which are not converted to an active form in the upper airways (ciclesonide), may be of use. The specialists agreed that, at low doses, there was a low risk of systemic adverse effects with ICSs. The Committee concluded that there is little difference in the clinical effectiveness of different products when delivered appropriately at low doses. |
| 4.3.5 | Clinical specialists noted that higher doses of ICSs (greater than 800 micrograms beclometasone dipropionate equivalent) were associated with a higher risk of systemic adverse events, such as osteoporosis, although the extent of this risk was poorly quantified and based on observational studies with conflicting results. The specialists agreed that people?s treatment should be initiated and maintained on the lowest possible dose of ICS that controls their symptoms. They expressed concern that some people may be on inappropriately high doses of ICSs because treatment has been ?stepped up? during an exacerbation but not ?stepped down? when good control of asthma was achieved. Based on the evidence from RCTs, the Committee considered there to be little difference in the adverse-event profile of the different ICSs at comparable doses and concluded that people should be treated with the lowest effective dose of ICS. |
| 4.3.6 | The Committee considered the different types of inhaler devices in line with technology appraisal guidance 38. The Committee considered that this guidance remains appropriate and was based on an assessment of good-quality evidence regarding the effective deposition of ICSs in the lower respiratory tract. The specialists agreed with the Committee that this guidance on young asthmatics would also apply to the use of ICSs in adults and that, where appropriate, a press and breathe pMDI with a spacer should normally be the device of first choice. Additionally the Committee heard from clinical specialists that, for ICSs, a pMDI and spacer device is usually considered in the first instance in routine clinical practice. The specialists noted, however, that despite training, a sizeable proportion of people (up to approximately 50%) are not able to use a pMDI alone effectively. Patient experts also stated that some people did not use the spacer device because they consider them to be cumbersome, and they do not believe that they need a spacer device to effectively deliver the drug. |
| 4.3.7 | The Committee considered evidence on the relative cost effectiveness of the different ICS products for the treatment of asthma. The Committee was aware of the variation in the price of different manufacturer?s products of the same ICS and the variation in price of the different types of inhaler devices. The Committee concluded that, in light of the presumed equivalence of the clinical effectiveness of the different ICS products, the least costly product that can be used effectively by an individual should be used. |
| 4.3.8 | The Committee considered the RCT evidence on the addition of a LABA to ICS treatment in people who are not adequately controlled on an ICS alone at step 3 of the BTS/SIGN guidelines. The Committee noted that the addition of a LABA to the current dose of ICS is more clinically effective than increasing the dose of ICS (in the absence of a LABA). The Committee considered that treatment with an ICS plus LABA in a single combination inhaler was at least as effective as using the same ingredients in separate inhalers. It also noted that there were no consistent differences between the two combination inhalers currently available in terms of clinical effectiveness. The Committee heard from clinical specialists and patient experts that the use of a single combination inhaler for the administration of an ICS plus LABA is associated with significantly improved adherence compared with the use of two separate inhalers. They also suggested that when two separate inhalers are prescribed, there is a risk that the ICS may be forgotten or not used for a variety of reasons, including concern over the use of an ICS in general and the immediate bronchodilator effect of the LABA detected by patients. The Committee was also aware that LABAs are licensed only for use in people with asthma who are already taking an ICS. The Committee was persuaded that, from the point of view of clinical effectiveness in people for whom treatment with an ICS and LABA is appropriate, use of a single combination inhaler would normally be preferred to the use of two separate inhalers. However, the Committee agreed that there might be circumstances when separate devices in fully compliant individuals could be equally clinically effective and equally or more cost effective. |
| 4.3.9 | The Committee considered the evidence on the cost effectiveness of ICS plus LABA treatment using a single combination inhaler or separate inhalers. The Committee noted that the use of a combination inhaler (ICS plus LABA) can be cost saving compared with using separate inhalers. The Committee also considered that, in people for whom ICS plus LABA treatment is appropriate, the least costly delivery method should be used, which is currently a single combination inhaler. However, the Committee was aware that future changes in the availability and relative cost of generic ICSs, LABAs and combination products (ICS plus LABA in a single device) may alter the relative cost effectiveness of delivery using a single combination inhaler compared with separate inhalers so that, in the future, delivery via separate inhalers in fully compliant individuals may become the preferred option. However, based on the current availability and relative pricing of combination inhalers, the Committee was persuaded that, at present, combination inhalers would be preferable. The Committee also noted that using a single combined inhaler decreased the prescription cost for the individual. |
| 5 | Implementation |
| 5.1 | The Healthcare Commission assesses the performance of NHS organisations in meeting core and developmental standards set by the Department of Health in ?Standards for better health? issued in July 2004. The Secretary of State has directed that the NHS provides funding and resources for medicines and treatments that have been recommended by NICE technology appraisals normally within 3 months from the date that NICE publishes the guidance. Core standard C5 states that healthcare organisations should ensure they conform to NICE technology appraisals. |
| 5.2 | 'Healthcare Standards for Wales? was issued by the Welsh Assembly Government in May 2005 and provides a framework both for self-assessment by healthcare organisations and for external review and investigation by Healthcare Inspectorate Wales. Standard 12a requires healthcare organisations to ensure that patients and service users are provided with effective treatment and care that conforms to NICE technology appraisal guidance. The Assembly Minister for Health and Social Services issued a Direction in October 2003 which requires Local Health Boards and NHS Trusts to make funding available to enable the implementation of NICE technology appraisal guidance, normally within 3 months. |
| 5.3 | NICE has developed tools to help organisations implement this guidance (listed below). These are available on our website (www.nice.org.uk/TA XXX). [Note: tools will be available when the final guidance is issued] |
| 6 | Related NICE guidance |
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NICE is developing the following guidance (details available from www.nice.org.uk).
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| 7 | Proposed date for review of guidance |
| 7.1 | The review date for a technology appraisal refers to the month and year in which the Guidance Executive will consider whether the technology should be reviewed. This decision will be taken in the light of information gathered by the Institute, and in consultation with consultees and commentators. |
| 7.2 | It is proposed that the guidance on this technology is considered for review in November 2012. A five year review date is proposed as it is not expected that further research will substantially change the recommendation of this appraisal. The Institute would particularly welcome comment on this proposed date. |
| David Barnett |
| Chair, Appraisal Committee |
| March 2007 |
| Appendix A. Appraisal Committee members and NICE project team |
| A. Appraisal Committee members |
| The Appraisal Committee is a standing advisory committee of the Institute. Its members are appointed for a 3-year term. A list of the Committee members who took part in the discussions for this appraisal appears below. The Appraisal Committee meets three times a month except in December, when there are no meetings. The Committee membership is split into three branches, each with the chair and vice-chair. Each branch considers its own list of technologies and ongoing topics are not moved between the branches. |
| Committee members are asked to declare any interests in the technology to be appraised. If it is considered there is a conflict of interest, the member is excluded from participating further in that appraisal. |
| The minutes of each Appraisal Committee meeting, which include the names of the members who attended and their declarations of interests, are posted on the NICE website. |
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Dr Jane Adam Professor AE Ades Anne Allison Dr Tom Aslan Professor David Barnett (Chair) Mrs Elizabeth Brain Dr Karl Claxton Dr Richard Cookson Mrs Fiona Duncan Professor Christopher Eccleston Dr Paul Ewings Professor John Geddes Mr John Goulston Mr Adrian Griffin Ms Linda Hands Dr Rowan Hillson Professor Philip Home (Vice Chair) Dr Terry John Professor Richard Lilford Dr Simon Maxwell Dr Alec Miners Ms Judith Paget Dr Ann Richardson Mr Mike Spencer Dr Simon Thomas Mr David Thomson Dr Norman Vetter Dr Paul Watson |
| B. NICE project team |
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Each technology appraisal is assigned to a team consisting of one or more health technology analysts (who act as technical leads for the appraisal), a technical adviser and a project manager. Eleanor Donegan and Elangovan Gajraj Janet Robertson Alana Miller |
| Appendix B. Sources of evidence considered by the Committee | |
| A |
The assessment report for this appraisal was prepared by Peninsula Technology Assessment Group (PenTAG), Peninsula Medical School and Southampton Health Technology Assessments Centre (SHTAC), Wessex Institute for Health Research and Development (WIHRD), University of Southampton. Shepherd J, Rogers G, Anderson R et al. ICS and LABAs for the treatment of chronic asthma in adults and children aged 12 years and over: Systematic review and economic analysis, December 2006 |
| B | The following organisations accepted the invitation to participate in this appraisal. They were invited to make submissions and comment on the draft scope and assessment report. They are also invited to comment on the appraisal consultation document (ACD). Consultee organisations have the opportunity to appeal against the final appraisal determination: |
| I |
Manufacturer/sponsors:
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| II |
Professional/specialist and patient/carer group/other groups:
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| III |
Commentator organisations (without the right of appeal):
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The following individuals were selected from clinical expert and patient advocate nominations from the professional/specialist and patient/carer groups. They participated in the Appraisal Committee discussions and provided evidence to inform the Appraisal Committee?s deliberations. They gave their expert personal view on corticosteroids for the treatment of chronic asthma in adults and children aged 12 years and over by attending the initial Committee discussion and/or providing written evidence to the Committee. They are invited to comment on the ACD:
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This page was last updated: 30 March 2010