I've talked about my form to manage in another post;
1- if I don't see the name of one player during a match (usually MC's, and ST's as a 2nd option) I change this near the minute 55-60
2- If one ST, as a first option, (MC as a second but not always), do lots of shoots, and fail all, I change this player too in the 60' aprox.
The 3rd substitute is used near the minute 80, if I win, I try to protect my better player of an injury.