Personalized medicine in biomarker identification at their optimal cut-off selection.

Introduction: Retrospective exploratory analysis to identify biomarker pairs in the AVAGAST Phase III study. Aim: The main hypothesis of this retrospective exploratory biomarker analysis is the identification of dichotomization levels based on optimal selection driven by the predictive value of single biomarkers. The outcome of interest optimization might unveil additional treatment benefits. Furthermore, testing the biomarker pairs at their optimal cut-off selection might provide the predictive score candidates. Material and methods: 712 plasma 92% and 727 plasma 94% tumor samples of all patients were using Cox model by identifying optimal dichotomization to maximize treatment benefit. A quadrant analysis grouped biomarker pairs into subsets yielded the best clinical benefit. Candidate biomarker score using the nested 2-fold cross-validation method was used to adjust the optimal cut-off selection. Results: Patients with lower VEGF-R1 at optimal cut-off with low IHER2G showed significant improvement in PFS - first line (HR = 0.62; 95% CI: 0.50 to 0.78). The interaction p-value of the biomarker pair was adjusted at 0.0147094. Conclusions: The predictive biomarker is a potential candidate for PFS - first line in patients with advanced gastric cancer treated with Bevacizumab.

Revealed preferences towards the appraisal of orphan drugs in Poland - multi criteria decision analysis.

BACKGROUND: A Multi Criteria Decision Analysis (MCDA) technique was adopted to reveal the preferences of the Appraisal Body of the Polish HTA agency towards orphan drugs (OMPs). RESULTS: There were 34 positive and 23 negative HTA recommendations out of 54 distinctive drug-indication pairs. The MCDA matrix consisted of 13 criteria, seven of which made the most impact on the HTA process. Appraisal of clinical evidence, cost of therapy, and safety considerations were the main contributors to the HTA guidance, whilst advancement of technology and manufacturing costs made the least impact. CONCLUSIONS: MCDA can be regarded as a valuable tool for revealing decision makers' preferences in the healthcare sector. Given that only roughly half of all criteria included in the MCDA matrix were deemed to make an impact on the HTA process, there is certainly some room for improvement with respect to the adaptation of a new approach towards the value assessment of OMPs in Poland.