definiens: means, in relation to the CombiD Study, all of the following : ( a ) that Statistical Significance is achieved for the Overall Survival Endpoint ; ( b ) that the FDA accepts or agrees that Statistical Significance has been achieved forthe Overall Survival Endpoint ; and ( c ) the absence of a New Material Safety Signal ; ( ii ) means both of the following : ( a ) in relation to the CombiD Study, both : 52 ( A ) achievement of a point estimate for the Hazard Ratio ( HR ) on the OverallSurvival Endpoint that is [ * * * ] or better ( that is, lower than [ * * * ] ) ; and ( B ) the absence of a New Material Safety Signal ; and ( b ) the FDA not disallowing, within 12 months of Conclusion of the CombiD Study, continued use in the product insert of the claim that the Combination is moreefficacious than the constituent mono - therapies ; ( iii ) means the later of ( i ) the date that is 12 months afterConclusion of the CombiD Study, and ( ii ) 31 December 2015 ; ( iv ) means the Phase III, randomized, double - blinded study comparing thecombination of the BRAF inhibitor, dabrafenib and the MEK inhibitor, trametinib to dabrafeniband placebo as first - line therapy in subjects with unresectable ( Stage IIIC ) or metastatic(Stage IV ) BRAF V600E / K mutation - positive cutaneous melanoma ( the ) ; ( v ) means when the Overall Survival Endpoint is analysed and the CombiD Studyis closed ; ( vi ) means a Safety Signal : ( a ) which is identified in the results of the CombiD Study ; ( b ) which was not described in the approval of the Combination by the FDA or therespective approvals of the BRAF and MEK components of the Combination ; and ( c ) in respect of which, within 12 months of the Conclusion of the CombiD Study, theFDA requires inclusion of a on the product insert for the Combination, theBRAF inhibitor and the MEK inhibitor ; ( vii ) means, as defined in the study protocol for the CombiD Studyand the statistical analysis plan agreed with the FDA in respect thereof, the time fromrandomization until death due to any cause, where : ( a ) all - cause mortality is used and censoring is performed using the date of the lastknown contact for those who were alive at the time of analysis ; and ( b ) overall survival is summarized using the Kaplan - Meier method and treatmentcomparisons are made using a stratified log rank test ( stratified by LDH status andmutation status ) ; 53 ( viii ) means information that arises from one or multiple sources that suggests anew, potentially causal association, or a new aspect of a known association, between anintervention and event or set of related events, which is adverse ; and ( ix ) means a one - sided p - value less than [ * * * ]