This is a legacy issue with EA's football games in general. Full disclosure, this is the first Madden I've played since maybe Madden 10. I am loving it overall but over the past 5 years, most of my video game time has gone to FIFA. I drifted away from NCAA as the series went through its last few versions and really was never too into Madden, but got bit by the football bug this year and played it on Access and loved it. My point here is this- the last NCAA and EA football game I played before Madden 17 was NCAA 12. Before that I was an annual NCAA guy. Over the years and I distinctly remember this in 12 as well, this exact issue was present in the game logic.
I had 2 very good running backs on my roster my first season of dynasty and wanted to get them both out there as much as I could, so I adjusted the Auto Subs. A poster on these boards explained the issue very well to me then and it was more or less this. Fatigue/stamina depreciates over the course of a game. Players start the game at full 100 stamina, and over the course of the game it naturally decreases. So for example, maybe after the first quarter, if you ran the ball with the same back a lot, he'd be down to 85. To simulate real life, they designed it so that when players rested on the sidelines, they would regenerate their stamina, but only to a certain extent. So maybe this back takes the first series of the 2nd quarter off and is back to 90 stamina. This makes sense in real life, as you can rest up and be subbed out, but you won't get back to full 100% fresh during the course of the game. This leads to the problem with Auto Subs. Once a player falls below the stamina sub in threshold and has reached the point in the game where their stamina will not regenerate to that required rating, the game effectively has sent to the locker room for the remainder of the game. Ill try to be more clear about this below.
So for example, if you have sub in/sub out at say 90/85, this means that a player has to have 90 stamina to sub in I believe. But after a certain point in the game and running a certain number of plays, it becomes impossible for a player whose played enough to be eligible under the games logic to be subbed in again. If your stamina can never get to 90 again in that game, then the game makes the player disappear, as he has to have 90 to be subbed in.
This is a longtime issue with these games and incredibly frustrating that it is still around, especially for those who want to run with multiple backs and split carries like their real life counterparts will do. I am not sure what the solution was back in the old days, other than manually sub in players from the menus yourself and leave the auto subs at default. Obviously this is a big issue for simming/play the moment though.