What is the proper way to run the spyware detection programs

The procedure should be followed as written when you are having problems that you cannot get cleaned up by normal methods (including scanning in normal mode). So many times you can just do weekly or bimonthly scans in normal boot mode. Many problems can be found and cleaned in normal boot. Some stubborn ones require safe mode. There are also times when certain problems do no show themselves at all in safe mode. These are exceptions to the rule and may require that you at least boot in normal mode to find them. Cleaning this type can prove to be more challenging.