In CTCAE, Grade refers to the severity of adverse events. Generally, Grade 1 events are mild; Grade 2 are moderate; Grade 3 are severe; Grade 4 are lifethreatening or disabling; Grade 5 is death. CTCAE grading is by definition a 5- point scale generally corresponding to mild, moderate, severe, life-threatening and death. This grading system inherently places a value on the importance of an event, although, there is not necessarily "proportionality" among grades (a "2" is not necessarily twice as bad as a "1"). Some adverse events are difficult to "fit" into this 5 point schema, but altering the general guidelines of severity scaling would render the system useless for comparing results between trials, an important purpose of the system. Some AES do not have a value for every Grade (e.g., Grade 4 hiccups is blank).