Inpharma 1587 - 12 May 2007

Insulin glargine adds up to value for diabetes in the UK– Kimberley Salmon –

Reimbursement, or ‘fourth hurdle’ requirements for new medicines are now becoming more internationallywidespread. As such, appraisal committees must respond in "an appropriate and timely manner" to newevidence regarding drugs and diseases, and "fairly consider evidence from beyond the artificial confines" of therandomised, controlled trial (RCT), contend Dr Simon Dixon from Sheffield University, UK, and Dr John R Petersfrom University Hospital of Wales, Cardiff, UK.1 They feature as guest editors in a supplement of Current MedicalResearch and Opinion, in which their editorial accompanies four original studies evaluating the costeffectiveness of insulin glargine for diabetes mellitus (DM). The studies were all financially supported by sanofi-aventis, and viewed together, "are examples of how the current system of economic appraisal of healthtechnology and its dogmatic reliance on RCT evidence may not be in the best interests of patients", say Drs Dixonand Peters.

NPH insulin were found to be "very similar" to the"Highly cost effective" in type 1 DMoriginal NICE estimate, confirming NICE’s originalInsulin glargine treatment is "highly cost effective"decision, they declare.relative to neutral protamine Hagedorn (NPH) insulin for

patients with type 1 diabetes in the UK, regardless of "Value for money" in type 2 DMwhether a reduction in hypoglycaemia or an Insulin glargine also seems to be cost effective for allimprovement in glycaemic control is seen as the primary patients with type 2 diabetes, "not only those at high riskbenefit, conclude Dr Phil McEwan from Cardiff of hypoglycaemia as currently recommended by NICE",University, UK, and colleagues.2 This finding also say Drs Dixon and Peters.demonstrates that the 2002 decision by UK NICE to use Indeed, in a second modelling study conducted by Drinsulin glargine in the UK has been "vindicated", and that McEwan and colleagues, insulin glargine, whenthere has "likely been considerable health benefit to compared with NPH insulin, was found to representmany patients as a consequence". "good value for money" among patients with type 2

Dr McEwan and colleagues used a discrete event diabetes. 3

simulation (DES) model to evaluate the cost Dr McEwan and colleague again used a DES model,effectiveness of insulin glargine versus NPH insulin from populated with data obtained from the UKPDS studythe perspective of the UK NHS, using either reduced and other published literature, to assess the costhypoglycaemia or improved glycaemic control as the effectiveness of insulin glargine versus NPH insulinprimary benefit. These benefits were considered in among patients with type 2 diabetes from theorder to update the 2002 UK NICE evidence used to perspective of the UK NHS. Cost items (reported insupport the NICE appraisal committee’s original 2005 values) included insulin regimens, and treatmentdecision to reimburse insulin glargine for patients with of hypoglycaemia, macrovascular events, retinopathy,type 1 diabetes in the UK. blindness, nephropathy and peripheral vascular disease;

The DES model was constructed using pooled data discount rates of 3.5% were applied to both costs andobtained from RCTs and other published literature. outcomes.Costs associated with medical treatment were derived In the base-case analysis, the model followed a cohortfrom UK sources and converted to 2005 values; costs of 1000 patients with type 2 diabetes in each arm overwere those related to insulin treatment, hypoglycaemia, 40 years. Under a scenario in which only a difference inmacrovascular events, retinopathy, blindness, hypoglycaemia was considered, total per-patient costsnephropathy, peripheral vascular disease, and and gains in QALYs were estimated at £6433 and £4892ketoacidosis. Where necessary, costs and benefits were and 7797 and 7686 for insulin glargine and NPH insulin,discounted at a rate of 3.5% per annum. respectively.

The subsequent ICER for insulin glargine versus NPH"Very similar" to NICE’s estimateinsulin under this scenario would be £10 027 per QALYConsidering a cohort of ≤ 10 000 patients withgained. Under a second scenario, in which differences indiabetes over a maximum of 40 years, the modelHbA1c were also considered, the mean ICER wasshowed that insulin glargine would have an incrementalestimated at £13 921 per QALY gained for insulincost per quality-adjusted life-year (QALY) gained ofglargine versus NPH insulin, Dr McEwan and colleaguesbetween £3189 and £9767 (discounted). These figuresnote. These ICER values are within commonly acceptedwould depend on the effectiveness data used in thethresholds for treatments that are regarded as "providingbase-case analysis, and the assumed utility decrementvalue for money" by NICE, they comment. Moreover,associated with hypoglycaemia. A detailed sensitivitythe model’s results were "upheld under a range ofanalysis showed that the majority of mean incrementalplausible scenarios", state Dr McEwan and colleagues.cost-effectiveness ratios (ICERs) for insulin glargine

versus NPH insulin were within £20 000 per QALY THIN data flesh out findingsgained. On balance, insulin glargine shows a marginal

Drs Dixon and Peters note that the DES model used improvement in diabetes-related outcomes, comparedby Dr McEwan and colleagues is "considerably more with insulin detemir, according to the results of a studysophisticated " than the deterministic models developed conducted by Dr Craig J Currie from Cardiff University,as part of the 2002 NICE appraisal of insulin glargine.1 UK, and associates.4

However, the resulting ICERs for insulin glargine versus

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Single Article

Insulin glargine adds up to value for diabetes in the UK – continuedfor both the insulin glargine and insulin detemir cohortsTable 1: Median antidiabetic prescription costs per (625 and 268 with type 1 diabetes, and 977 and 334person-year (£) for patients with type 1 diabetes in with type 2 diabetes, respectively).the UK

Prescription type Insulin glargine Insulin detemir Table 2: Median antidiabetic prescription costs (£) (n = 625) (n = 268)per person-year for patients with type 2 diabetes in

Insulin (cartridges and 776.46 853.70 the UKpens)Prescription type Insulin glargine Insulin detemirHypoglycaemia rescue 33.39 44.22

(n = 977) (n = 334)medicationReagents 332.85 381.86 Insulin (cartridges and 628.44 920.43Sharps 63.35 84.93 pens)Pen delivery services 58.36 96.61 Oral antidiabetics 43.68 37.10Total antidiabetic costs 1197.68 1330.10 Hypoglycaemia rescue 23.43 35.43

medicationReagents 221.43 263.25

Proprietary data obtained from The Health Sharps 68.82 82.46Improvement Network (THIN) were used to compare Pen delivery services 54.79 108.91the actual clinical outcomes of two of the most recently Total antidiabetic costs 1013.51 1410.31launched basal insulin analogue products, insulinglargine and insulin detemir in routine clinical practice in

The analysis showed that the antidiabetic prescribingthe UK. Data were abstracted for a total of 6378 diabeticcosts were "significantly lower" among patients treatedpatients, 3142 of whom had type 1 diabetes, over awith insulin glargine versus insulin detemir, saytimeframe of ≤ 15 years. The two alternative treatmentsDr Poole and colleagues [see tables 1 and 2].* Thesewere compared for 9 months by quarterly periodsfindings have "clear policy implications in thatfollowing switching to one of these treatments.preferential treatment with glargine over detemir" wouldDue to different launch dates, a greater number ofresult in "substantial cost savings to the payer" forpatients in the study received insulin glargine thanpatients with both type 1 and type 2 diabetes, theyinsulin detemir (5683 vs 694), note Dr Currie anddeclare. Indeed, under the same assumptions employedassociates. Following the switch to either therapy, therein the analysis, for 1000 patients, an overall cost savingwas a 30% reduction in the rate of reportedof £132 000 per year would be expected for insulinhypoglycaemia in the insulin glargine group, comparedglargine versus detemir use in type 1 diabetes, andwith a 9% reduction in the insulin detemir group.£397 000 in type 2 diabetes.However, while insulin detemir was associated with

Drs Dixon and Peters point out that the analysis"almost no weight gain on average" in the first 6 monthsconducted by Dr Poole and colleagues illustrates theof treatment, insulin glargine was associated with an"potential strength of using real-life data in economicaverage gain of 0.5kg per patient over the same period,evaluations as opposed to RCTS".1note Dr Currie and associates. Neither of these

outcomes reached statistical significance, they * Reference prices for costs were taken from the March 2006 DrugTariff, and included those related to insulin acquisition, cartridges forcomment. Nevertheless, these findings "potentially haverefillable pens, disposable per-filled pens, reagent test strips,policy implications", they contend, as conclusivehypoglycaemia rescue medication, sharps (syringes, needles andevidence of insulin glargine’s clinical superiority would lancets), and pen delivery services.

"impact on the relative cost effectiveness of the two1. Dixon S, et al. Evaluating the real cost-effectiveness of health technology:alternative treatments". Importantly, these data would

reconciling the public interest with patients’ interests. Current Medical Researchalso infer that is "also vital to collate intelligence post- and Opinion 23 (Spec. issue 1): 1-6, 2007.

2. McEwan P, et al. Evaluation of the cost-effectiveness of insulin glargine versuslaunch about new drugs and treatments to complementNPH insulin for the treatment of type 1 diabetes in the UK. Current Medicalthe intelligence derived from clinical trials", Dr Currie Research and Opinion 23 (Spec. issue 1): 7-19, 2007.

and associates declare. 3. McEwan P, et al. Evaluation of the cost-effectiveness of insulin glargine versusNPH insulin for the treatment of type 2 diabetes in the UK. Current Medical

"Clear policy implications" Research and Opinion 23 (Spec. issue 1): 21-31, 2007.4. Currie CJ, et al. The outcome of care in people with type 1 and type 2 diabetesIn a sister analysis, the same group of researchers, this

following switching to treatment with either insulin glargine or insulin detemirtime led by Dr Chris D Poole from threesixtydegree in routine general practice in the UK: a retrospective database analysis. Current

Medical Research and Opinion 23 (Suppl. 1): 33-39, 2007.Research Ltd, Penarth, UK, used data obtained from the5. Poole CD, et al. The prescription cost of managing people with type 1 and typeTHIN database to assess differences in the prescribing 2 diabetes following initiation of treatment with either insulin glargine or insulin

costs associated with insulin glargine and insulin detemir in routine general practice in the UK: a retrospective database analysis.Current Medical Research and Opinion 23 (Spec. issue 1): 41-46, 2007.detemir.5

801069466The date of marketing authorisation for insulindetemir in the UK (1 June 2004) defined the earliest date

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