Health Technology Assessment 2004; Vol 8: number 45
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E Warren, E Weatherley-Jones, J Chilcott* and C Beverley
ScHARR Technology Assessment Group, School of Health and Related Research, University of Sheffield, UK
* Corresponding author
The aim of this review was to evaluate the use of insulin glargine in its licensed basal-bolus indication in terms of both clinical and cost-effectiveness.
A systematic review of the literature, involving a range of databases, was performed to identify all papers relating to insulin glargine.
Nineteen studies met the inclusion criteria but full reports were available for only six.
For type 1 diabetes patients, insulin glargine appears to be more effective than neutral protamine Hagedorn (NPH) in reducing fasting blood glucose (FBG) but not in reducing glycosylated haemoglobin (HbA1c) and there is some evidence that both insulins are as effective as each other in both FBG and HbA1c control. For type 2 patients for whom oral antidiabetic agents provide inadequate glycaemic control, there is no evidence that insulin glargine is more effective than NPH in reducing either FBG or HbA1c and some evidence that both insulins are as effective as each other in both FBG and HbA1c control.
Evidence for control of hypoglycaemia is equivocal. In studies where insulin glargine is demonstrated to be superior to NPH in controlling nocturnal hypoglycaemia, this may be only apparent when compared with once-daily NPH and not twice-daily NPH. Further, this superiority of glargine over NPH in the control of nocturnal hypoglycaemia may relate to one formulation of insulin glargine (HOE901) and not another (HOE901). There is no conclusive evidence that insulin glargine is superior to NPH in controlling symptomatic hypoglycaemia and severe hypoglycaemia. Insufficient data are available to conclude whether insulin glargine is different from each of the commonly used NPH dosing regimens: once daily and more than once daily.
There are no published economic studies on insulin glargine or indeed NPH insulin. An economic evaluation of insulin glargine has been provided in the Aventis submission. Given the lack of a published evidence base for the cost-effectiveness of insulin glargine, the economic review concentrates on a review of the industry submission and an amended ScHARR model. Three economic models are provided in the submission, two relating to type 1 diabetes (previously on other basal-bolus regimes or previously on premix therapies) and one relating to type 2 diabetes. All three models compare the costutility of insulin glargine against NPH insulin. In general, the structures of the models are poor. In all three models, mistakes relating to assumptions and calculations have been made. The industry submission concludes that insulin glargine is highly cost-effective in all three models. The incremental cost per quality-adjusted life year (QALY) ratios generated by the company models are presented in the first table.
|Model||Base-case cost per QALY (£)||Base-case cost per QALY (£)|
|Type 1 (other basal-bolus)||1,1481,292||79245,853|
|Type 1 (premix)||Dominant||Dominant9,509|
Based on the evidence presented, there appears to be no rationale for the two separate models within type 1 diabetes. No evidence has been presented that suggests type 1 patients previously receiving premix therapies would experience better glycaemic control on insulin glargine than patients previously treated by other basal-bolus regimes.
An evaluation of the industry model was made and a separate model was constructed. The assessment team believe that the cost per QALY estimates generated by the Aventis model may be an underestimate for several reasons:
Information from the Aventis submission was submitted in confidence to NICE. This information was made available to the NICE Appraisals Committee but has been removed from this version of the report.
The incremental cost per QALY ratios generated from the assessment team models are presented in the second table.
|Patient group||Base-case cost per QALYa (£)||Cost per QALY range (£)|
|a Cost per QALY ratio depends on the method on administration (vial, cartridge or insulin pen).|
The cost-effectiveness of insulin glargine in both type 1 and type 2 diabetes is highly sensitive to the amount of utility associated with reducing the fear of hypoglycaemia. The industry submission explores this issue through a number of analyses and the claimed base case is based on the most favourable of these analyses. By changing this assumption, the cost per QALY ranges from cost-effective to not cost-effective.
The evidence suggests that, compared with NPH insulin, insulin glargine is effective in reducing the number of nocturnal hypoglycaemic episodes, especially when compared with once-daily NPH. There appears to be no improvement in long-term glycaemic control and therefore insulin glargine is unlikely to reduce the incidence of the long-term microvascular and cardiovascular complications of diabetes.
Further research into insulin glargine is needed in these key areas:
Warren E, Weatherley-Jones E, Chilcott J, Beverley C. Systematic review and economic evaluation of a long-acting insulin analogue, insulin glargine. Health Technol Assess 2004;8(45).
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