The principle problem becomes depth of knowledge.
The longer the run the wider the variety of table layouts and shots that must be shot. And, as the run lengthens, the likelihood of difficult situations that take more knowledge, experience, and skill to overcome, occurs more often.
IOWs, play a few racks and you might not see anything too terrible. Keep going a few more racks and maybe the balls don't open up so well. A few more and maybe you misplay your position or pattern. More racks and perhap you need to manufacture a break ball. More racks and maybe you have to break the balls off a difficult 15th ball. And then there is maintaining focus -- let it wander just a bit and maybe you miss a ball or a positional play you'd normally make.
Wash, rinse and repeat.
That's an interesting observation. I like that.
Beyond the usual missed shot, missed position, and just bad luck, there have been many times I wondered if the balls could be replaced in the 'post-break' position, how often the player would choose an alternative path through the rack.