From the rules page...
The coach will sometimes use his own judgment to decide what the proper balance is between starters, backups, reserves, and even players on the bench but not in the depth chart at all.
You can set the balance between how much coaches use their own judgment or defer to yours with the substitutions box. You can use entirely your judgment (Strictly Follow Depth Chart), entirely the coach's judgment (Let Coach Decide), a mix between the two (Coach Picks from Depth Chart), or you can use your depth chart strictly until the 4th quarter, then tell the coach to try and win the game however he thinks is best (Depth Chart until 4th).