Diabetes (type 1 and 2), Inhaled Insulin - Appraisal consultation document
Appraisal Consultation Document
Inhaled insulin for the treatment of diabetes (types 1 and 2)
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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 inhaled insulin for the treatment of diabetes (types 1 and 2) and provide guidance on its 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 inhaled insulin for the treatment of diabetes (type 1 and 2). 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 this technology. 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: Closing date for comments: 10 May 2006 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 |
| 1.1 | Inhaled insulin is not recommended for the treatment of type 1 or type 2 diabetes mellitus, except in the context of clinical studies designed to evaluate the clinical and cost effectiveness of inhaled insulin compared with injected insulin in people with diabetes whose blood sugar levels are uncontrolled with their current diabetes regimen. These studies should include relevant outcome measures to evaluate quality of life. |
| 2 | Clinical need and practice |
| 2.1 | Diabetes mellitus is a chronic metabolic disorder caused by defects in insulin secretion and action. It is associated with acute metabolic disturbances such as hyperglycaemia (high blood glucose) and ketoacidosis, which is caused by severe insulin deficiency and can result in coma. If prolonged, hyperglycaemia can cause microvascular and macrovascular damage. Microvascular complications result from damage to small blood vessels and include diabetic retinopathy (visual impairment), nephropathy (kidney damage) and neuropathy (nerve damage). Macrovascular complications result from damage to large blood vessels and include heart disease and foot ulceration. |
| 2.2 | It is estimated that there are over 2 million people with diabetes in the UK, of which approximately 80% have type 2 diabetes. Around 90,000 people are newly diagnosed each year. Type 1 diabetes generally affects younger people. Type 2 diabetes usually appears in people over the age of 40 years, but it often appears earlier in South Asian and African-Caribbean people. |
| 2.3 | The key goal in the management of diabetes is the normalisation of blood glucose levels. Current guidelines recommend that treatment should aim to achieve a level of haemoglobin A1c (HbA1c) of between 6.5% and 7.5%. |
| 2.4 | In type 1 diabetes, the pancreas makes little or no insulin, and individuals usually depend on daily insulin injections to survive. There are three main types of insulin preparations: (1) short-acting, which have a relatively rapid onset of action; (2) intermediate action and (3) long-acting, which have a slower onset of action and act for long periods. The duration of action of a particular type of insulin varies considerably from one patient to another, and needs to be assessed individually. Insulin is generally given by subcutaneous injection into the layer of tissue immediately beneath the skin. Short-acting insulins can also be given by continuous subcutaneous infusion using a portable infusion pump. This device delivers a continuous basal insulin infusion and patient-activated bolus doses at meal times. |
| 2.5 | NICE guidelines state that the insulin regimen for people with type 1 diabetes should be tailored to meet the needs of the individual, including taking into account preference for number of injections. People with type 1 diabetes often need to adjust their dosage on a day-to-day basis in order to achieve optimal control. A common management strategy for type 1 diabetes is the basal-bolus regimen; the use of a short-acting insulin before each meal (the ?bolus? or mealtime dose), and long-acting insulin at bedtime (the ?basal? dose). Alternatively, pre-mixed insulin regimens can be used, which contain a fixed mixture of short- and intermediate-acting insulin; this is more convenient but cannot be adjusted easily. Under certain circumstances, continuous subcutaneous insulin infusion via an insulin pump may be used. |
| 2.6 | Type 2 diabetes results from reduced insulin production and/or reduced tissue sensitivity to insulin (insulin resistance). Type 2 diabetes is managed initially through diet and exercise. As the disease progresses, most individuals require oral anti-diabetic drugs to maintain satisfactory blood glucose levels. However, when the disease further progresses, insulin therapy may be necessary. The 2002 NICE guideline on the management of blood glucose in people with type 2 diabetes concluded that there was little research evidence available about optimal insulin regimens and recommended that local experience, patient preference and relative costs should inform the choice of insulin type and regimen. |
| 2.7 | Some people with diabetes experience problems with insulin injections. A recent study identified problems related to the frequency of injections, locating suitable injection sites, pain, fear of needles and a dislike of injecting in public. |
| 3 | The technology |
| 3.1 | Inhaled insulin (Exubera, Pfizer Ltd) is inhaled, rapid-acting, dry-powder, human insulin produced by recombinant DNA technology. It should be administered before meals and as part of a daily treatment regimen that also includes once-daily injected long-acting insulin or oral anti-diabetic drugs. It has a UK marketing authorisation for the treatment of adults with type 1 diabetes, in addition to long- or intermediate-acting subcutaneous insulin, for whom the potential benefits of adding inhaled insulin outweighs the potential safety concerns. It also has a UK marketing authorisation for the treatment of adults with type 2 diabetes not adequately controlled with oral anti-diabetic agents and requiring insulin therapy. |
| 3.2 | Inhaled insulin is administered via the pulmonary route using a specifically designed hand-held inhaler device. This allows the insulin to be delivered to the alveoli in the lungs, from where it is absorbed into the bloodstream. |
| 3.3 | The most commonly observed side effects are hypoglycaemia and mild cough, which appears to decrease over time. There is also uncertainty about lung damage with long-term use. It is stated in the Summary of Product Characteristics that people with diabetes must have stopped smoking at least 6 months before starting Exubera therapy and must not smoke during therapy with Exubera. Exubera is contraindicated in people with poorly controlled, unstable or severe asthma, or severe chronic obstructive pulmonary disease. |
| 3.4 | The cost of the inhaled insulin regimens is based on the assumption that people with diabetes would need to receive 0.15 mg of insulin per kg of body weight per day. Using an average weight of 76.5 kg and 83.7 kg for people with type 1 and type 2 diabetes, respectively, a dosage of 13 mg/day and a unit cost of £0.23/mg, the annual cost can be estimated to be £1102. This cost includes the device. Costs may vary in different settings because of negotiated procurement discounts. |
| 4 | Evidence and interpretation |
| The Appraisal Committee considered evidence from a number of sources (see appendix B). | |
| 4.1 | Clinical effectiveness |
| 4.1.1 | The Assessment Group identified five randomised controlled trials (RCTs) in type 1 diabetes and two in type 2 diabetes. The manufacturer identified the same studies in type 2 diabetes, but only four of the studies in type 1 diabetes. However, the manufacturer added two different studies in type 1 diabetes, which the Assessment Group did not include. The duration of the studies ranged from 12 to 52 weeks, and a total of 2204 people were enrolled. All studies included people who were stable on their current insulin regimen (entry HbA1c value was in the range 5?11%) and who used at least two injections of insulin per day. None of the studies compared inhaled insulin with continuous subcutaneous infusion or with regimens using rapid-acting insulin analogues. Only two studies compared regimens, which varied only in terms of bolus insulin, with basal insulin being kept standard between the inhaled and control groups. Most studies gave little or no detail of patients recruited and had a large number of exclusion criteria. |
| Diabetes control | |
| 4.1.2 | The primary outcome measure was change in HbA1c. This reflected the average blood glucose level over the preceding 3 months, as a measure of how well the diabetes was controlled . |
| 4.1.3 | In six of the seven RCTs in type 1 diabetes, the relative risk (RR) of HbA1c < 7.0% with inhaled insulin compared with short-acting subcutaneous insulin was: 0.80 (95% confidence interval [CI] 0.33 to 1.91), 0.99 (95% CI 0.59 to 1.66); 1.06 (95% CI 0.70 to 1.59); 0.73 (95% CI 0.60 to 0.88); 1.53 (95% CI 0.90 to 2.60); and 0.77 (95% C.I 0.57 to 1.03). In the seventh study, the mean change from baseline HbA1c was +0.1% for short-acting subcutaneous insulin and ?0.3% for inhaled insulin. |
| 4.1.4 | In the two RCTs in type 2 diabetes, the RR of HbA1c of < 7.0% with inhaled insulin compared with short-acting subcutaneous insulin was 1.49 (95% CI 1.10 to 2.00) in the first study, and the mean change from baseline HbA1c was ?0.7% for both short-acting subcutaneous and inhaled insulin in the second study. |
| 4.1.5 | The manufacturer undertook a meta-analysis of six of the identified RCTs in type 1 diabetes. The pooled RR of HbA1c < 7% with inhaled insulin compared with short-acting subcutaneous insulin was 0.89 (CI 0.72 to 1.10). The Assessment Group undertook a meta-analysis of two of these trials and found that the weighted mean difference in change from baseline in HbA1c between the two groups was 0.09 (?0.20 to 0.37). |
| Adverse events | |
| 4.1.6 | In the RCTs in type 1 diabetes, compared with short-acting subcutaneous insulin, inhaled insulin was found to be associated with a slightly lower RR of overall hypoglycaemic episodes in two studies: RR = 0.96 (95% CI 0.93 to 0.99) and RR = 0.94 (95% CI 0.91 to 0.97), respectively. Similar rates were found in four studies, in which the RRs were: 1.17 (95% CI 0.98 to 1.40); 1.01 (95% CI 0.99 to 1.04); 1.05 (95% CI 0.96 to 1.15); and 1.00 (95% CI 0.97 to 1.03). A higher rate was found in one study: RR = 1.24 (95% CI 1.17 to 1.31). |
| 4.1.7 | In the two RCTs in type 2 diabetes, which compared inhaled insulin with short-acting subcutaneous insulin, one reported no difference in hypoglycaemic episodes, and the other reported a slightly lower risk of overall hypoglycaemic episodes (RR = 0.89, 95% CI 0.82 to 0.97). |
| 4.1.8 | All seven studies in type 1 diabetes reported on severe hypoglycaemic events. Of these, two studies identified a higher risk of severe hypoglycaemic event with inhaled insulin than with short-acting subcutaneous insulin: RR = 2.00 (95% CI 1.28 to 3.12) and RR = 2.87 (95% C.I 0.32 to 25.55). Four studies found similar rates of severe hypoglycaemic events in the two treatment groups, with RRs of: 1.29 (95% CI 0.38 to 4.40), 1.18 (95% CI 0.78 to 2.00), 1.16 (95% CI 0.76 to 1.76), and 0.77 (95% CI 0.56 to 1.06). One trial reported fewer severe hypoglycaemic episodes with inhaled insulin compared with short-acting subcutaneous insulin: RR = 0.52 (95% CI 0.30 to 0.86). |
| 4.1.9 | The manufacturer undertook a meta-analysis of six of the trials in type 1 diabetes. The pooled RR (inhaled insulin vs short-acting subcutaneous insulin) was found to be 1.01 (95% CI 0.99 to 1.03) for hypoglycaemic events and 0.93 (95% CI 0.74 to 1.16) for severe hypoglycaemic events. |
| 4.1.10 | Both trials in type 2 diabetes reported similar rates of severe hypoglycaemic events between treatment groups. No events were reported in any treatment group in one study, and in the other study the rate of severe hypoglycaemic events was 0.5 per patient month for inhaled insulin and 0.1 per patient month for subcutaneous insulin. |
| 4.1.11 | Data on other adverse events were cited, including pulmonary function, carbon monoxide diffusing capacity and cough. No significant differences between intervention groups in terms of any pulmonary outcome were identified. Four studies reported a greater incidence of cough with inhaled insulin, but the cough appeared to be mild and decreased during the study period. Some RCTs reported a significantly greater mean decrease in carbon monoxide diffusing capacity for inhaled insulin. The assessment report stated that higher insulin antibody levels observed in the inhaled insulin groups in the trials did not result in any apparent clinical change. |
| 4.1.12 | Of the six RCTs in type 1 diabetes that reported on weight change, none identified any statistically significant differences between inhaled and short-acting subcutaneous insulin. In the studies in type 2 diabetes, one study found a statistically significantly greater weight gain with short-acting subcutaneous insulin (adjusted mean group difference ?1.29 kg (95% CI -1.98 to ?0.59). The second study found no difference between treatment groups. The manufacturer?s meta-analysis of studies involving people with type 1 diabetes or insulin-experienced people with type 2 diabetes reported a statistically significant greater gain in body weight with short-acting subcutaneous insulin, compared with inhaled insulin (adjusted mean group difference ?0.74 kg (95% CI ?1.02 to ?0.47 kg). |
| Patient satisfaction | |
| 4.1.13 | Five trials (three involving people with type 1 diabetes and two involving insulin-experienced people with type 2 diabetes) reported on patient satisfaction, measured using the Patient Satisfaction with Insulin Therapy Questionnaire. All five trials showed statistically significantly greater satisfaction with the inhaled insulin regimen (in overall satisfaction and most subscales). The manufacturer?s meta-analysis identified a pooled difference in overall satisfaction of 24.3 (95% CI 18.14 to 30.44) in favour of inhaled insulin. |
| Quality of life | |
| 4.1.14 | Three RCTs reported on quality of life (two in type 1 diabetes and one in type 2 diabetes). All reported that overall quality of life and subscales showed more favourable improvement among people taking inhaled insulin (p < 0.05). |
| Patient preference | |
| 4.1.15 | Two trials reported on patient preferences (one in type 1 diabetes and one in type 2 diabetes). Both found that patients on inhaled insulin were statistically significantly more likely to prefer to continue with the insulin modality they received during the trial compared with patients who had received subcutaneous insulin. |
| 4.1.16 | An additional RCT was identified, which involved people with type 2 diabetes in whom dietary control and/or oral hypoglycaemic agents therapy had failed to achieve target glycaemic control. One group of patients was given written information about existing treatment options (oral hypoglycaemic agents and subcutaneous insulin). A second group received the same information plus details of the risks and benefits of inhaled insulin. Both groups were then asked to make choices about future diabetes therapy. When the choices of insulin therapy included inhaled insulin, 43% chose to start insulin, and 35% chose inhaled insulin. In the group for which inhaled insulin was not an option, only 15.5% opted for (subcutaneous) insulin. |
| 4.2 | Cost effectiveness |
| 4.2.1 | The Assessment Group and the manufacturer?s submission did not identify any published cost effectiveness studies on inhaled insulin. |
| 4.2.2 | The manufacturer?s submission provided an economic analysis. This was based on a probabilistic Monte Carlo simulation model, using a modified Markov process with yearly intervals and a 20-year time horizon. This model was validated against the study data used in the development of the model itself (internal validation) and showed that all model results were within a +/- 10% deviation. External validation was undertaken against studies not used in the model?s construction. |
| 4.2.3 | Only patients with uncontrolled diabetes (HbA1c > 7.4%) were considered in the model. It was assumed that inhaled and subcutaneous basal-bolus insulin regimens achieve the same level of blood glucose control. Compliance was assumed to be 100%. All patients were assumed to be non-smokers, to have a medium level of physical activity, and to be Caucasian. In addition to the cost of insulin and glucose monitoring, a cost of £25/year was added to the annual cost of inhaled insulin in order to take into account the annual spirometry tests that may be required. |
| 4.2.4 | Based on a hypothetical study carried out in insulin-naïve people with diabetes, it was assumed that 35% of people with poorly controlled diabetes in the inhaled insulin arm of the model would move to inhaled insulin therapy immediately, and the remaining 65% would start inhaled insulin 4 years later. For the modelling of the control arm (subcutaneous insulin), it was assumed that 15% of people with poorly controlled diabetes would move to subcutaneous insulin immediately, and the remaining 85% would start subcutaneous insulin 4 years later. |
| 4.2.5 | Utility gains from the use of inhaled insulin compared with subcutaneous insulin, used in the manufacturer?s model, were derived from a utility elicitation study in 132 people with type 1 diabetes and 212 people with type 2 diabetes using the time-trade-off method and the EQ5D method. The values derived from the time-trade off method suggested a substantially higher benefit than the values derived by the EQ5D method. The model used the utility gains derived from the time-trade-off method. |
| 4.2.6 |
In the manufacturer?s model, patient subgroups were analysed on the basis of their current treatment regimen as follows:
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| 4.2.7 | The Assessment Group did not develop a separate model but re-ran the manufacturer?s model using alternative assumptions on estimates of utility decrements associated with complications (such as heart failure, stroke, end-stage renal disease, peripheral vascular disease and minor amputation). The Assessment Group used a 2-year delay for the take up of insulin treatment in the base-case scenarios, rather than a 4-year delay used in the manufacturer?s submission. |
| 4.2.8 |
The Assessment Group modelled only two different type 2 diabetes patient populations.
Furthermore, the Assessment Group explored alternative scenarios with regard to patient age and duration of diabetes (patients aged 40, 50 and 60 years were assumed to have durations of diabetes of 5, 8 and 12 years, respectively). |
| 4.2.9 | The Assessment Group reviewed the utility gains derived from inhaled insulin compared with injected insulin used in the manufacturer?s analysis. The Assessment Group thought that it was not intuitively clear that the use of inhaled insulin would be sufficient to result in utility gains similar to avoiding blindness in one eye or diabetic foot syndrome. Using the EQ5D profiles from the manufacturer?s utility elicitation study, the Assessment Group reanalysed the utility gains using different assumptions on the likelihood of severity ratings. As a consequence, the utility value from the use of inhaled insulin was judged to be more likely to lie below 0.02, which is more in line with some published data. |
| 4.2.10 | The Assessment Group calculated the cost effectiveness for inhaled insulin assuming greater and earlier acceptance of insulin therapy alone (without any change in health-related quality of life, that is, utility gain 0.00) and also assuming an increase in health-related quality of life from taking insulin by inhalation rather than injection (utility gains 0.02 and 0.04). |
| 4.2.11 | When only the greater and earlier acceptance of insulin therapy alone was considered with no utility gain, the ICERs were above £200,000 for both scenarios and all age groups analysed. When a utility gain of 0.02 was used, the ICERs were above £30,000 for all groups analysed, apart from patients with type 2 diabetes currently uncontrolled on a subcutaneous basal regimen and compared with moving to basal-bolus, for which the ICERs were around £21,000 for all age groups considered. When a utility gain of 0.04 was used, the ICERs were between £22,000 and £24,000 for patients with type 2 diabetes currently uncontrolled on an oral regimen and between £10,000 and £17,000 for patients with type 2 diabetes currently uncontrolled on a subcutaneous basal regimen . |
| 4.2.12 | Both the manufacturer?s analysis and the Assessment Group?s modelling contained various sensitivity analyses, using alternative assumptions on discount rate, costs data, compliance data and uptake of insulin. These sensitivity analyses did not lead to substantially different ICERs. |
| 4.2.13 | In summary, the manufacturer?s analysis led to much lower ICERs than the Assessment Group?s analysis. This is likely to be a result of the more favourable utility gains from the use of Exubera that were used in the manufacturer?s submission. |
| 4.3 | Consideration of the evidence |
| 4.3.1 | The Committee reviewed the data available on the clinical and cost effectiveness of inhaled insulin for the treatment of diabetes (types 1 and 2), having considered evidence on the nature of the condition and the value placed on the benefits of inhaled insulin by people with diabetes mellitus, those who represent them, and clinical experts. It was also mindful of the need to take account of the effective use of NHS resources. |
| 4.3.2 | The Committee sought the opinion of the clinical and patient experts about the likely level of need for inhaled insulin in clinical practice. The experts advised the Committee that using injected insulin is not usually a concern for the majority of people with diabetes, given the availability of patient support and education, modern small needle types and insulin pens. The experts also pointed out that the availability of inhaled insulin would not completely replace the need for injections of insulin for most people with diabetes, and that inhaled insulin might not fully alleviate any problems relating to true needle phobia, because individuals would still need to use needles for glucose testing. |
| 4.3.3 | However, the Committee understood that there were reasons why some individuals, who need to improve their glycaemic control, were reluctant either to start insulin therapy or to intensify injection regimens. For example, some people with type 2 diabetes are concerned about hypoglycaemic attacks, or believe that the move to insulin injections represents a failure on their part with oral therapy, or think that the change in therapy indicates that their diabetes has become much worse. Some people with diabetes may also be concerned about the impact of using insulin on their driving licence status and employment, but these concerns would be equally relevant with inhaled insulin. The Committee also heard from the clinical and patient experts that a small group of people with diabetes are so averse to injections for psychological or cultural reasons that they would rather face the prospect of diabetic complications than use subcutaneous insulin. |
| 4.3.4 | The Committee discussed the use of inhaled insulin in people with type 1 diabetes, many of whom need to adjust their dosage on a day-to-day basis in order to achieve optimal control. It was pointed out by the patient experts that the inhaled insulin device does not allow patients to adjust their insulin dose sufficiently. This limitation may lead to difficulties in glucose control compared with injections. |
| 4.3.5 | The Committee considered the evidence on clinical effectiveness and was persuaded that inhaled insulin can be regarded as effective in controlling HBA1c levels as short-acting subcutaneous insulin (as used in the RCTs). However, concerns were raised regarding the methods of the reported RCTs, none of which compared inhaled insulin with current standard care in the UK, which uses a range of alternative injection therapies including insulin pens, insulin analogues and insulin glargine. The methods used limit the assessment of the generalisability of the results to routine clinical practice. In addition, none of the RCTs examined the effectiveness of inhaled insulin exclusively in people whose blood glucose levels are uncontrolled on their current regimen. |
| 4.3.6 | The Committee also discussed the uncertainties regarding the long-term safety of inhaled insulin in terms of potential pulmonary effects and the reported higher levels of insulin antibodies in people with type 1 diabetes. |
| 4.3.7 | The Committee concluded that the evidence for the effect of inhaled insulin on patient satisfaction and preference was crucial to the cost-effectiveness analysis. The Committee agreed that the effects on patient preference would only be relevant to this appraisal if they translated into proven utility gain and changes in health-related quality of life. |
| 4.3.8 | The Committee expressed concerns about the methods and generalisability of the manufacturer?s studies used to show patient preferences and, in particular, the hypothetical nature of the data and the lack of strength of preferences expressed. The estimation of probable take up of inhaled insulin was questioned on several grounds: because the available hypothetical study was among people with type 2 diabetes on diet or oral hypoglycaemic therapy, who made theoretical choices about whether to use inhaled insulin; because it was not stated whether all alternative options (such as night-time single injections or the use of insulin pens) were explored; and because detailed information on recruitment procedures, which would be needed in order to assess the likely validity of the results, was not available. The Committee considered that, outside the RCT setting, patients may state an initial preference for inhaled insulin, but some may reconsider when they become aware of the size of the device, the time taken to set it up, and the fact that its use is less discreet and may be less flexible than other methods of blood glucose control. |
| 4.3.9 | The Committee discussed the ICERs derived from the manufacturer?s analysis, which were all below £17,000/QALY and based on utility gains of 0.04 or more. The Committee concluded that the utility values suggested in the manufacturer?s submission were unlikely to be realistic in clinical practice. Although the Committee was not fully persuaded by the Assessment Group?s approach to the utility estimation, it concluded that, on balance, a utility gain from moving from an injected to an inhaled formulation of more than 0.02 across the entire population of patients with diabetes was unproven, taking into account comparisons with published utility values for other conditions. |
| 4.3.10 | The Committee considered the effect of improved and earlier acceptance of insulin therapy on the cost effectiveness of inhaled insulin. It understood that delays in moving to insulin treatment could have important effects on avoidance of the long-term complications of diabetes. However, the Committee concluded from the Assessment Group?s economic modelling of type 2 diabetes that this effect alone was insufficient to provide support for a cost-effective use of this technology. Therefore, cost effectiveness was entirely dependent on the magnitude of the utility gain derived from inhaled insulin compared with injected insulin. |
| 4.3.11 | The Committee was persuaded that inhaled insulin could be cost effective in people with diabetes who experience a true and severe fear of insulin injections and who refuse to accept injected insulin therapy despite a high risk of complications. However, the Committee considered that the evidence base currently available did not enable it to evaluate the clinical effectiveness of inhaled insulin with any certainty in this context. Additionally, the Committee was not persuaded that there was a clear way to identify the characteristics of patient who would gain sufficient benefit for this technology to be cost-effective. |
| 4.3.12 | Given the evidence on clinical effectiveness and cost effectiveness, the Committee concluded that inhaled insulin should not be recommended for the diabetic (type 1 or type 2) population as a whole. Furthermore, inhaled insulin should not be recommended for patients whose blood glucose levels remained uncontrolled because of a very strong aversion to insulin injections. The Committee reached this conclusion is because there is (1) currently insufficient evidence of clinical effectiveness in this patient group and (2) uncertainty about how to identify this patient group in routine clinical practice with the accuracy necessary to ensure cost effectiveness. |
| 4.3.13 | The Appraisal Committee concluded that further research is needed to assess the clinical and cost effectiveness of inhaled insulin compared with injected insulin in people with diabetes whose blood sugar levels are uncontrolled with their current diabetes regimen. Studies with relevant outcome measures to evaluate effects on quality of life are particularly needed. The Committee therefore recommended that treatment with inhaled insulin should be offered only as part of appropriately designed clinical trials. |
| 5 | Proposed recommendations for further research |
| 5.1 | The Committee noted that there was an ongoing trial, the Exubera Real World Classic, to assess the impact of inhaled insulin on glycaemic control in people with poorly controlled type 2 diabetes receiving two or more oral anti-diabetic agents. |
| 5.2 | The Committee recommends research into the effectiveness of inhaled insulin to improve compliance and glycaemic control in people with diabetes whose blood sugar levels are uncontrolled with their current diabetes regimen. The comparators should be current best practice, which includes insulin analogues and intensification of subcutaneous insulin, including a support programme. These studies should also report on relevant measures of quality of life that can make a valid contribution to the assessment of clinical and cost effectiveness of inhaled insulin compared with injected insulin in this specific patient group. |
| 5.3 | Additionally, the Committee recommends research into the characteristics and prevalence of patient groups whose blood sugar levels remain uncontrolled because they do not comply with current treatment regimens. |
| 6 | Preliminary views on the resource impact for the NHS |
| The NICE Costing Unit is currently developing this section. A costing template and report will be available at the time of publication of the final guidance. |
| 7 | Proposals for implementation and audit |
| This section presents proposals for implementation and audit based on the preliminary recommendations for guidance in section 1. | |
| 7.1 | NHS organisations and clinicians who care for people who have diabetes mellitus should review their current practice and policies to take account of the guidance set out in section 1. |
| 7.2 | Inhaled insulin is not used in the treatment of people with type 1 or type 2 diabetes mellitus, except in the context of clinical studies designed to evaluate the clinical and cost effectiveness of inhaled insulin compared with injected insulin in people with diabetes whose blood sugar levels are uncontrolled with their current diabetes regimen. These studies should include relevant outcome measures to evaluate quality of life. |
| 8 | Related guidance |
| 8.1 |
The National Institute for Clinical Excellence issued the following related technology appraisal guidance/clinical guidelines. National Institute for Clinical Excellence (2003) Guidance on the use of continuous subcutaneous insulin infusion for diabetes. NICE technology appraisal guidance no. 57. London: National Institute for Clinical Excellence. Available from: www.nice.org.uk/TA057 National Institute for Clinical Excellence (2003) Guidance on the use of glitazones for the treatment of type 2 diabetes. NICE technology appraisal guidance no. 63. London: National Institute for Clinical Excellence. Available from: www.nice.org.uk/TA063 National Institute for Clinical Excellence (2003) Guidance on the use of patient-education models for diabetes. NICE technology appraisal guidance no. 60. London: National Institute for Clinical Excellence. Available from: www.nice.org.uk/TA060 National Institute for Clinical Excellence (2002) Guidance on the use of long-acting insulin analogues for the treatment of diabetes - insulin glargine. NICE Technology Appraisal Guidance no. 53. London: National Institute for Clinical Excellence. Available from: www.nice.org.uk/TA053 National Institute for Clinical Excellence (2004) Type 1 diabetes: Diagnosis and management of type 1 diabetes in children, young people and adults. NICE Inherited Clinical Guideline No.15 . London: National Institute for Clinical Excellence. Available from: www.nice.org.uk/CG015 National Institute for Clinical Excellence (2002) Management of type 2 diabetes. Renal disease ? prevention and early management. NICE Inherited Clinical Guideline F . London: National Institute for Clinical Excellence. Available from: www.nice.org.uk/page.aspx?o=27924 National Institute for Clinical Excellence (2002) Management of type 2 diabetes. Retinopathy ? screening and early management. NICE Inherited Clinical Guideline E . London : National Institute for Clinical Excellence. Available from: www.nice.org.uk/page.aspx?o=27922 National Institute for Clinical Excellence (2002) Management of type 2 diabetes. Management of blood glucose. NICE Inherited Clinical Guideline G . London: National Institute for Clinical Excellence. Available from: www.nice.org.ukpage.aspx?o=36727 National Institute for Clinical Excellence (2002) Management of type 2 diabetes. Management of blood pressure and blood lipids. NICE Inherited Clinical Guideline H . London: National Institute for Clinical Excellence. Available from: www.nice.org.uk/page.aspx?o=38564 |
| 9 | Proposed date for review of guidance |
| 9.1 | 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. |
| 9.2 | It is proposed that the guidance on this technology is considered for review in April 2009. The Institute would particularly welcome comment on this proposed date. |
| David Barnett |
| Chair, Appraisal Committee |
| April 2006 |
| Appendix A. Appraisal Committee members | |
| 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 twice a month except in December, when there are no meetings. The Committee membership is split into two branches , with the chair, vice-chair and a number of other members attending meetings of both branches. 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. | |
| Dr Jane Adam Radiologist, St George's Hospital, London |
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| Professor A E Ades MRC Senior Scientist, MRC Health Services Research Collaboration, Department of Social Medicine, University of Bristol |
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| Dr Tom Aslan General Practitioner, Stockwell, London |
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| Professor David Barnett (Chair) Professor of Clinical Pharmacology, University of Leicester |
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| Mrs Elizabeth Brain Lay Representative |
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| Dr Karl Claxton Health Economist, University of York |
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| Dr Richard Cookson Senior Lecturer in Health Economics, School of Medicine Health Policy and Practice, University of East Anglia |
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| Mrs Fiona Duncan Clinical Nurse Specialist, Anaesthetic Department, Blackpool Victoria Hospital, Blackpool |
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| Professor Christopher Eccleston Director, Pain Management Unit, University of Bath |
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| Dr Paul Ewings Statistician, Taunton and Somerset NHS Trust, Taunton |
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| Professor John Geddes Professor of Epidemiological Psychiatry, University of Oxford |
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| Mr John Goulston Director of Finance, Barts and the London NHS Trust |
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| Mr Adrian Griffin Health Outcomes Manager, Johnson & Johnson Medical Ltd |
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| Ms Linda Hands Consultant Surgeon, John Radcliffe Hospital |
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| Dr Elizabeth Haxby Lead Clinician in Clinical Risk Management, Royal Brompton Hospital |
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| Dr Rowan Hillson Consultant Physician, Diabeticare, The Hillingdon Hospital |
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| Dr Catherine Jackson Clinical Lecturer in Primary Care Medicine, Alyth Health Centre, Angus |
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| Professor Richard Lilford Professor of Clinical Epidemiology, Department of Public Health and Epidemiology, University of Birmingham |
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| Dr Simon Mitchell Consultant Neonatal Paediatrician, St Mary's Hospital, Manchester |
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| Ms Judith Paget Chief Executive, Caerphilly Local Health Board, Wales |
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| Dr Katherine Payne Health Economist, The North West Genetics Knowledge Park, The University of Manchester |
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| Dr Ann Richardson Independent Research Consultant |
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| Dr Stephen Saltissi Consultant Cardiologist, Royal Liverpool University Hospital |
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| Mr Mike Spencer General Manager, Clinical Support Services, Cardiff and Vale NHS Trust |
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| Professor Andrew Stevens (Vice Chair) Professor of Public Health, University of Birmingham |
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| Dr Cathryn Thomas General Practitioner, and Associate Professor, Department of Primary Care and General Practice, University of Birmingham |
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| Dr Norman Vetter Reader, Department of Epidemiology, Statistics and Public Health, College of Medicine, University of Wales, Cardiff |
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| Professor Mary Watkins Professor of Nursing, University of Plymouth |
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| Dr Paul Watson Medical Director, Essex Strategic Health Authority |
| A. NICE Project Team |
| Each appraisal of a technology is assigned to a Health Technology Analyst and a Technology Appraisal Project Manager within the Institute. |
| Helen Tucker and Elisabeth George Technical Lead, NICE project team |
| Sarah Garner Technical Advisor, NICE project team |
| Alana Miller Project Manager, NICE project team |
| Appendix B. Sources of evidence considered by the Committee | ||
| A. |
The assessment report for this appraisal was prepared by the University of Aberdeen.
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| 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) and consultee organisations are provided with the opportunity to appeal against the final appraisal determination (FAD).
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| C |
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 inhaled insulin in diabetes mellitus 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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