Yes, it is OKAY to make changes in OverDriveNTool while the miner is running.  Let's say you have 4 Vega cards and one is the proverbial mutt.  If you are using the Jericho Jones script, you might opt to have the script load a pretty conservative, lower hashing rate OverDriveNTool profile just so that Cast or XMR start mining smoothly.  Then you can go into OverDriveNTool and apply a different profile for the three cards that work great, one by one, while the miner is running.  You should see changed hash rates for those cards in under a minute.  Or you could create two different profiles, and load the slower one for the mutt card, and the better one for the three good cards using the VideoTools option explained within the script and at the vegaminingblog.

Changing settings in OverDriveNTool while the miner is running can help you determine which card(s) is or are the dog(s) (your miner will crash after you hit "apply" for that card, even if it did not crash for the other cards).

You can fine tune your setup in this way.  But be aware that OverDriveNTool numbers the cards differently than the miner program.  So change one card's settings and see which card # in the miner window is affected.