In the read-option, the QB "reads" the DE (OLB in 3-4). If the DE takes a step outside to contain the QB, then the QB hands off. If the DE takes a step inside to contain the RB, then the QB keeps the ball and moves to the outside with the option to run or pass.
In theory, the DE is always wrong because he made his move before the hand-off or lack of hand-off.
There have been many articles about how college defenses handle the RO. My understanding is that the most successful college defenses had a pre-snap call that determined how the DE would handle the play. If the other 10 defenders know ahead of time that the DE will be following the QB, then they basically know that the RB will get the ball and vice-versa.
If the DE always follows the QB, then the RB will continually get the ball against a defense that basically has 1 man less (the DE) than they would against a normal running play. The reason for the pre-snap defensive call is to keep the offensive from knowing which action the DE will take.
Another thing that the successful college defenses do is to have the DE fake his action. The DE could fake his 1st step to the inside and immediately move back outside to chase the QB. At this point, it can become a timing game between the DE and the QB. If the QB makes his "read" to early, then the DE's fake could be more successful.
In the NFL, they have announced that once the QB keeps the ball in the read-option, he is then considered a RB not a QB and is no longer operating under QB protection rules.