Time To Replace Tubes?

I was wondering when do you guys decide to change your tubes?Are there any indications to listen for to know that you are at the end of your time with a set of tubes short of them blowing up on you?
I have a Wright 3.5 that has the 2a3,6sn7 and 5y3 rectifier tube in it.I was using a set of NOS Brimar's in the 6sn7 position.Recently i started thinking my mids were not there in my system and thought that my newly acquired modwright Sony 999ES may have been part of the problem.Well on a whim i swapped back in the stock EH6sn7's that came with the amp.I have very low hours on those tubes as i put the Brimars in not long after getting the Wright's.WEll my lordy the soundstage became huge and warm and just awesome just with swapping back in those EH's.
Maybe they just work better synergistically with the Modwright player i don't know.Maybe the Brimars are still fine but sounded lean with this player?
But back to my original thought on this is there something you can audibly listen for when you know your tubes are going?
Now i wonder if replacing the 2a3 or the 5y3 will bring even more sonic gains?It sounds incredibly better now just with that 6sn7 swap.I was looking into new speaker wire and possibly a tube preamp and here all i really needed to get those mid guts were to put back in those EH's.I'm loving that too cause they are a heck of alot cheaper then the NOS route.
What a pleasant surprise!! : )