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Patients with anaplastic lymphoma kinase-positive (ALK+) advanced non–small-cell lung cancer should benefit from targeted therapy. The effect of increased use of an immunohistochemical technique was estimated using a health care–economics analysis. Extensive use of D5F3 has resulted in a diagnostic costs decrease. These savings could be reinvested to test a greater number of patients (53% vs. 75%). Reinvesting the saving would lead to an overall survival gain (+20%).To ensure identification of anaplastic lymphoma kinase-positive (ALK+) patients, the Italian Drug Agency suggested a testing algorithm based on the use of fluorescence in situ hybridization (FISH) and/or immunohistochemistry. The aim was to evaluate the clinical and economic effects of adopting an immunohistochemical test (Ventana ALK D5F3) as an option for detecting ALK protein expression in advanced non–small cell lung cancer (NSCLC) patients.A budget impact model was developed by adopting the Italian National Health Service (NHS) perspective and a 5-year period to compare 2 scenarios: the current use of D5F3 (28%; current scenario) and increased use of D5F3 (60%; alternative scenario). The testing cost and the number and cost of the identified ALK+ patients were evaluated.A more extensive use of D5F3 in the alternative scenario showed a decrease in diagnostic costs of ˜€468,000 compared with current scenario when considering all advanced NSCLC patients. If these savings were allocated to test more NSCLC patients (75% vs. 53%), an incremental cost per identified ALK+ patient of €63 would be required, leading to an overall survival gain for the alternative scenario compared with the current scenario (32.4 vs. 27.1 months; relative increase, 20%).The use of D5F3 would provide a cost savings for the NHS owing to a lower acquisition cost than FISH and a comparable detection rate. The savings could be reinvested to test a greater number of patients, leading to more efficient identification, use of targeted therapy, and improvement in clinical outcomes of ALK+ patients.