Our statistical approach adopted PFS as the primary outcome measure and involved ( i ) searching for biomarkers with prognostic relevance or which related to between-individual variation in bevacizumab effect ; ( ii ) unbiased determination of cutoffs for putative biomarker values ; ( iii ) investigation of biologically meaningfully predictive combinations of putative biomarkers ; and ( iv ) replicating the analysis on candidate biomarkers in the validation dataset .