4 Evidence

4.1 The systematic review included evidence on clinical effectiveness, ease of use, preference, compliance, and cost effectiveness.

Clinical effectiveness

4.2 Because of the specificity of device and drug effect, evidence for one drug in one device cannot be generalised to other drugs. Therefore, only research comparing the same drug (e.g. salbutamol vs salbutamol) at an equivalent dose level in different devices was considered. Studies including children aged 5–15 years were included in the review. Since the appraisal concerns device choice, rather than whether to treat using inhaler devices, placebo comparisons were not included. All studies included in the consideration of clinical effectiveness were randomised controlled trials (RCTs).

4.3 Evidence in this area is generally limited in quantity and quality. Only one relevant study comparing a breath-actuated device with other devices was found, and few studies considered devices delivering cromoglicates, long-acting ß2-agonists, or drugs in combination. Many of the available studies included fewer than 50 children, and were under-powered. The review found that studies claiming to demonstrate equivalence were often unable to do so, and that some studies used inappropriate dose comparators.

4.4 Three in vitro studies of drug delivery were identified, but these do not provide a sufficiently reliable basis for generalisation to device performance in children with asthma in clinical practice.

Delivery of bronchodilators

4.5 Twenty-three studies in the systematic review examined different devices in the delivery of bronchodilators.

Seven studies compared press-and-breathe pMDIs with and without spacers. In the main these included children, and all had fewer than 50 participants. Two of the studies found a significant difference in lung function favouring the pMDI and spacer combination. These were randomised cross-over studies, involving a total of 30 children aged between 5 and 14 years, that compared the delivery of terbutaline from a pMDI with delivery from a pMDI plus 750 ml collapsible spacer.

Thirteen studies compared press-and-breathe pMDIs (with or without spacer) with DPIs, and none demonstrated a statistically significant difference in lung function. Some of the studies used inappropriate dosing schedules, which may have biased their findings. Some studies included a high proportion of adults.

Three studies comparing different DPIs were included. They found no significant difference in lung function or symptoms, and all were small or included few children.

Delivery of anti-inflammatory drugs

4.6 Eight studies examined different devices for the delivery of corticosteroids. One used a filter method to compare a press-and-breathe pMDI in combination with one of two alternative spacers. It found significantly higher deposition of drug on the filters attached to a 250 ml metal spacer compared with a 750 ml plastic spacer. However, the study included only 16 children (aged 5 to 8 years), and found no difference in symptom scores between the two treatment groups.

Five studies compared press-and-breathe pMDIs (with or without spacers) with DPIs. One large well-designed study reported equivalence of a pMDI with spacer and a DPI at half of the drug dose used in the pMDI. However, the authors of a systematic review concluded that this finding did not represent evidence of advantage of the DPI over the press-and-breathe pMDI and large-volume spacer as the device of choice for the delivery of corticosteroids in childhood asthma. In addition, a filter collection study comparing a press-and-breathe pMDI plus spacer with a DPI in children aged 5–15 years reported significantly higher deposition in the DPI group, though no differences in lung function were reported. The remaining studies were of poor quality or were likely to have included few children.

Two adequately powered studies compared different DPIs, though neither reported a difference in effectiveness between devices.

One study compared a press-and-breathe pMDI with a breath-actuated pMDI for cromoglicate. No differences were found in lung function, but the study was under-powered.

CFC-free devices

4.7 The studies included in the review reported no evidence of difference in the effectiveness of devices using CFC-containing or CFC-free propellants in pMDIs. However, it is important to note that there are some reports of higher drug deposition of corticosteroids from HFA devices. Consequently it is possible that required doses may be different when transferring children from CFC to HFA inhalers.

Other influences on effectiveness

4.8 Thirty-one studies on ease of use, preference or compliance were included in the systematic review. However their quality was generally poor, and many devices have not been studied. Many of the studies did not involve direct device comparison, had fewer than 100 participants, included adults, or did not examine the actual impact of these factors on disease outcomes. Only 11 of the studies were RCTs.

4.9 A number of studies found that good individual (verbal) instruction was the key to correct inhaler technique, and two suggested that above age 5 or 6 years, this was the case regardless of the device. Studies on ease of use, adherence and preference are, however, of questionable value as the empirical value of these factors remains uncertain. Conclusions drawn from this body of research are likely to involve 'double counting', in that the effects of ease of use and preference may also contribute to compliance.

Cost effectiveness

4.10 No robust cost-effectiveness or utility studies examining use of inhalers in children aged 5–15 years with asthma were identified by the systematic review.

4.11 There are substantial differences in the acquisition costs of inhaler devices within the same drug dose range. For instance, in the delivery of one puff of salbutamol (ß2-agonist) a day, the lowest annual inhaler costs per device type are: press-and-breathe pMDI, £3.14; breath-actuated pMDI, £10.99; and DPI, £11.53. The highest cost for a DPI delivering salbutamol at this dose is £30.42.

Similarly, in the delivery of a 200ug dose of beclometasone (corticosteroid) a day, the lowest annual inhaler costs per device type are: press-and-breathe pMDI, £28.73; breath-actuated pMDI £28.73; and DPI £38.51. The highest cost for a DPI delivering beclometasone at this dose is £69.06. The annual costs of suitable spacer devices available on NHS prescription range from £4.28 to £8.56.

4.12 One study reported that the overall annual average cost of care for people with asthma who have not experienced an asthma attack in the past year was £108, compared with £381 for people who have had at least one attack over the same period. Higher costs in primary care contacts, hospital admissions and visits, and medication all contributed to the overall difference.

4.13 An economic analysis considering differences in overall costs between devices found that only small improvements in asthma outcomes were needed for a device to be considered cost-effective compared with the cheapest available alternative for the delivery of the same drug at the same dose. Consequently if, after taking account of the factors specified in section 1.1, a clinician considers that a particular device would be more likely to achieve good asthma control in a particular child than cheaper ones available, then that device should be chosen.

Consideration

4.14 The available evidence generally fails to distinguish adequately between devices to suggest significant advantage in clinical effectiveness for one single delivery system.

However, a limited amount of evidence supports the use of press-and-breathe pMDIs with large-volume spacers compared to press-and-breathe pMDIs alone in the delivery of bronchodilators, whilst one study reported equivalence of a press-and-breathe pMDI and large-volume spacer with a DPI at half the dose used in the pMDI in the delivery of a corticosteroid.

On balancing these findings, clinical opinion and pharmacological considerations, the Appraisal Committee concluded that press-and-breathe pMDIs and spacer devices have an important role to play in the delivery of corticosteroids in aiming to achieve optimal asthma control. Despite this, it was acknowledged that the effectiveness of any device depends on the willingness and ability of a child to use it and to adhere to an effective regimen. The aim should be to identify the most clinically appropriate device that the individual child will use, bearing in mind the need to minimise the systemic absorption of inhaled corticosteroids.

4.15 Economic analysis suggests that no device should be excluded on grounds of cost effectiveness; however, when more than one device is felt to satisfy the considerations set out in 4.14 in an individual child, the device with the lowest overall cost (i.e. considering daily required dose and product price per dose) should be chosen.

4.16 As there is limited evidence on the effectiveness of alternative spacers for a given inhaler, if a choice is available, the decision should be guided by information in the inhaler's Summary of Product Characteristics.