title: The cost effectiveness of rapid-acting insulin aspart compared with human insulin in type 2 diabetes patients: an analysis from the Japanese third-party payer perspective.
abstract: OBJECTIVE
  The Nippon Ultra-Rapid Insulin and Diabetic Complication Evaluation Study (NICE Study) (NCT00575172) was a 5-year, open-label, randomised controlled trial which compared cardiovascular outcomes in Japanese type 2 diabetes patients intensively treated with regular human insulin or insulin aspart (NovoRapid; Novo Nordisk A/S, Bagsvaerd, Denmark), a rapid-acting insulin analogue. The aim of the present analysis was to evaluate the cost effectiveness of insulin aspart versus regular human insulin from the perspective of a Japanese third-party healthcare payer.
  
  
  METHODS
  A discrete event-simulation model was developed in Microsoft Excel to assess the within-trial cost effectiveness and make longer-term clinical projections in patients treated with regular human insulin or insulin aspart. In addition to severe hypoglycaemia, the model captured myocardial and cerebral infarction events and percutaneous coronary intervention and coronary artery bypass graft procedures. Within-trial mortality, incidence of severe hypoglycaemia and cardiovascular event probabilities were derived from the annual rates observed during the trial period, while post-trial outcomes were calculated using the event rates from the trial, adjusted for increasing patient age. Event costs were accounted from the healthcare payer perspective and expressed in 2008 Japanese yen (JPY), while health-related quality of life (HRQoL) was captured using event and state utilities. Future costs and clinical benefits were discounted at 3% annually. Life expectancy, quality-adjusted life expectancy, cardiovascular event rates and costs were evaluated over 5- and 10-year time horizons and sensitivity analyses were performed to assess variability in model outcomes.
  
  
  RESULTS
  Over 5 years of treatment, insulin aspart dominated human insulin both in incremental life expectancy and in incremental quality-adjusted life-years (QALYS). Insulin aspart was associated with a small improvement in discounted life expectancy of 0.005 years (4.688 vs. 4.684 years) and an increase of 0.023 quality-adjusted life-years (QALYs) (3.800 vs. 3.776 QALYs) when compared with regular human insulin. Insulin aspart also incurred lower costs (JPY 481,586 vs. 594,717, difference -113,131) which resulted from the decreased incidence of cardiovascular events with insulin aspart (0.013 events per patient year vs. 0.030 on regular human insulin). Breakdown of costs indicated that pharmacy costs were higher with insulin aspart (JPY 346,608 vs. 278,468), but these costs were more than offset by the reduced costs associated with cardiovascular complications and hypoglycaemia over 5 years of treatment (JPY 134,978 vs. 316,249). Sensitivity analysis showed that insulin aspart was still cost-effective in the case where only 18% of the within-trial cardiovascular and mortality benefit over regular human insulin was captured in the model (assuming a willingness-to-pay threshold of JPY 5,000,000).
  
  
  CONCLUSIONS
  The NICE study cohort was relatively small (n = 325), meaning that caution should be exercised when calculating and interpreting the incremental cost-effectiveness ratio. Also, despite the differences in cardiovascular risk profile between the Japanese and UK populations, UKPDS-derived risk equations were used to project MI outcomes and PCI and CABG procedures and UKPDS HRQoL scores were applied to all health states. While these risk formulas and HRQoL utilities may not be directly applicable to the Japanese population, no equivalent Japanese-specific data are currently available.
  
  
  CONCLUSIONS
  In a Japanese type 2 diabetes population, prescribing rapid-acting insulin aspart significantly reduced cardiovascular complications over 5- and 10-year time horizons, resulting in increased quality of life and decreased costs when compared with human insulin.
authors.affiliation: Ossian Health Economics and Communications GmbH, Basel, Switzerland. pollock@ossianconsulting.com
authors.forename: R F
authors.initials: RF
authors.lastname: Pollock
authors.forename: W J
authors.initials: WJ
authors.lastname: Valentine
authors.forename: T
authors.initials: T
authors.lastname: Pilgaard
authors.forename: H
authors.initials: H
authors.lastname: Nishimura
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003362:Cost-Benefit Analysis / Q000191:economics; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000208:ethnology*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000191:economics* / Q000494:pharmacology / Q000627:therapeutic use; D007328:Insulin / Q000031:analogs & derivatives* / Q000191:economics* / Q000494:pharmacology / Q000627:therapeutic use; D061267:Insulin Aspart; D007349:Insurance, Health, Reimbursement; D007564:Japan / Q000208:ethnology; D008017:Life Expectancy; D008297:Male; D008875:Middle Aged
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D061267:Insulin Aspart