Benedetti, Massimo Massi, Valentine, William, Goodall, Gordon, Foos, Victor, Palmer, Andrew, Huebner, Reinhold, Luebben, Georg, and Pang, Francis
In PROactive (PROspective pioglitAzone Clinical Trial In macroVascular Events), a long-term cardiovascular (CV) events trial in patients with type 2 diabetes (T2D) and macrovascular disease, pioglitazone (PIO) was associated with a 10% reduction in the primary endpoint (P=0.09) and a 16% reduction in the key secondary cardiovascular endpoint (P=0.03) vs placebo (PBL) when administered on top of existing diabetes and CV therapies, including statins. The aim of this study was to apply PROactive outcome data to the validated CORE Diabetes Model (CDM) in order to estimate the long-term clinical and economic outcomes associated with PIO vs PLB for the German setting. The CDM was modified to accommodate data from PROactive and included 18 relevant disease and procedure specific interdependent Markov sub-models to simulate disease progression over patient lifetimes. Direct medical costs (treatment, management and complication) were derived from published German sources and expressed in 2005 Euros (€). Health utilities were taken from the Cost of Diabetes in Europe - Type 2 study (CODE-2). Clinical and economic outcomes were discounted at 5% per annum (per the Hannover Consensus Group Statement for Economic Evaluations). PIO was projected to have an additional discounted life expectancy of 0.172 years over PLB at an additional direct cost of €1,599 giving an incremental cost-effectiveness ratio (ICER) of €9,281 per life year gained. PIO was also associated with an additional 0.120 QALYs generating an ICER of €13,294 per QALY gained. Probabilistic sensitivity analysis demonstrated that, at a willingness to pay of €50,000 per QALY gained, there was a 78.2% probability of PIO being cost-effective. Univariate sensitivity analyses showed that the results were most sensitive to the time horizon and duration of PIO benefit. Addition of PIO to existing therapies in patients with T2D and pre-existing macrovascular disease leads to improved life expectancy, quality-adjusted life expectancy and reduced incidence of most diabetes-related complications compared to PLB. This health economic analysis demonstrates that the addition of PIO is cost-effective and is likely to represent good value for money in the German setting. [ABSTRACT FROM AUTHOR]