Analytical approach:
The analysis was based on an adapted version of the validated Center for Outcomes Research (CORE) Diabetes Model (Palmer, et al. 2004, see 'Other Publications of Related Interest' below for bibliographic details), which was developed to determine the long-term health outcomes and economic consequences of interventions in diabetes. A lifetime horizon (up to 35 years) was considered. The authors stated that the perspective was that of the third-party health care payer in Germany.
Effectiveness data:
The CORE Diabetes Model was adapted to incorporate the pioglitazone treatment. The main estimates of the treatment effectiveness, which were the event rates associated with macrovascular outcomes and the annual hazard ratios, over the short term (up to three years), and the patient baseline characteristics (demographics, risk factors, and complications) were derived from the PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive). This was a multinational, prospective, double-blind, placebo, randomised controlled trial (RCT), with 5,238 patients in 321 centres. Assumptions were required to extrapolate the clinical trial data to the patient's lifetime. The key model input was the change in glycated haemoglobin (HbA
1c) with pioglitazone, compared with placebo, at one, two, and three years and its impact on diabetes-related complications.
Monetary benefit and utility valuations:
The events in the PROactive were linked to health state utilities from the Cost of Diabetes in Europe – Type 2 (CODE-2) study (Bagust, et al. 2005, see 'Other Publications of Related Interest' below for bibliographic details), where possible, and ignored if it was not possible. The remaining utilities were those from the original model publication (Palmer, et al. 2004).
Measure of benefit:
The benefits were measured in quality-adjusted life-years (QALYs) and life-years (LYs) and these were discounted at a rate of 5% per annum.
Cost data:
The direct medical costs included the drugs, patient management (screening for retinopathy, nephropathy, and foot ulcers), and diabetes-related complications. Most of the resource use data were derived from the PROactive. All unit costs were in Euros (EUR), from published German sources, and discounted at a rate of 5% per annum. The price year was 2005.
Analysis of uncertainty:
The authors performed one-way sensitivity analyses on the key model parameters, including the discount rate, time horizon, change in HbA
1c, event rates, utility values, and unit costs. Several scenario analyses were conducted by including the quality of life utilities for events that were not included in the CODE-2 study (base case) and a worst-case scenario was examined using the most pessimistic values for the key event utilities. A Monte Carlo simulation, with 1,000 iterations was performed, using nonparametric bootstrapping, and the results were presented in a scatter plot and as a cost-effectiveness acceptability curve.