re combo trials Dew - you make great points. Although if vrtx can't hit great svrs in the tx-refractory prove-3 trial then perhaps the calculus changes and we do see combo trials sooner rather than later because 1. the unmet need in this group would still not be met 2. in that population there is a higher threshold for tolerance of side effects 2. vrtx will have plenty of naive trial data that is not tainted by more than one investigational compound