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You don't have to run out of i-form or whatever. You can and should call runs from 3wr/4wr formations just like you should call passes from 2wr formations. Having audibles you know like the back of your hand helps a lot as well.

Speaking of audibles, against a human I typically have a couple audibles out of my favorite formations at least 1 run and 1 pass for each. This way if they come out with too many linebackers I make sure I'm throwing or if I read blitz I can throw into the vacated area.

I especially like running singleback formations like 3wide where it clears out the middle a little bit.