Cross over in clinical trials skews up data. This however is a part and parcel of medical ethics. In the AVOREN trial following an interim analysis in December 2006, the superiority of Interferon plus Bevacizumab was significant enough that the study was unblinded and the Data Safety Monitoring Board recommended cross over of patients from placebo group to Bevacizumab group. Further approximately 63% of the patients in the Interferon and placebo group and 55% of the patients in the Interferon and Bevacizumab group went on to receive post protocol second and third line therapies with multitargeted Tyrosine Kinase Inhibitors (MKIs), mTOR inhibitors, cytokines and chemotherapy. This could have had an impact on overall survival results at the time of this analysis.