"I don't buy the long term effects reason because you can't prove it. If you see something happening to your fish a long time later it could have been almost anything from high nitrites, high nitrate, high this, high that, etc"
Some people still don't believe smoking causes lung cancer for a similar reason.
"For those who claim they saw instant death after using dose/fill directly method. Well was that your first time doing that? How about the previous times? What happened?"
I had that happen; so I'm a believer in the harm caused by in-tank mixing. I had an established 75G tank of small fish (e.g., rams, neons, guppies, swordtails, etc.). I was performing weekly water changes with a 5G bucket. I premixed the Prime in the bucket before dumping it in the tank. No fish loss after WCs for the year I did that. I then got a Python and during my first WC I added enough Prime for the whole tank and after the 25% change I lost a ram and a number of neons. The next water change I tried adding Prime while I was filling up the tank. Lost more fish. I also had another tank with African Cichlids that I was using the same procedure. I didn't loose any of them but I noticed that they shook their heads and flashed on the gravel during and ~ an hour after the change.
I then switched back to pre-mixing the Prime; this time using two 35G trash cans and a pump. No fish loss since, and I have not seen any of the Cichlids react to WCs; even after moving up to 50%.