This is a very easy answer. If you can't scope so that you have a very, very solid target on the work required to finish the project then you have to price it by time/materials.

There is no other sound way to do it and not lose your shorts. The bigger the project, the more the risk/variables, the more complex it is to scope.

I like the approach of "here are my best estimates of how far we'll be after 3/6/9 months, here is what it will cost, and here are the resources I have to commit to it. "

Cheers,
Ryan