Appendix Table 1.

Classification of AEs by Drug-Relatedness

Category	Definition
Definite	Any event occurring in a timely manner after administration of the study drug(s) that is a known sequela to the administration of the study drug(s) and follows a previously documented pattern of reaction but for which no other explanation is known. This category applies to AEs that the PI believes are incontrovertibly related to the study drug(s).
Probable	Any event occurring in a timely manner after administration of the study drug(s) that follows a known pattern of reaction to the study drug(s) and for which no other explanation is known. This category applies to AEs that, after careful medical consideration at the time they are evaluated, are believed with a high degree of certainty to be related to the study drug(s).
Possible	Any event occurring in a timely manner after administration of the study drug(s) that does not follow a known pattern of reaction and for which no other explanation is known. This category applies to AEs that, after careful medical consideration at the time they are evaluated, are considered unlikely to be related but cannot be ruled out with certainty.
Unlikely	In general, this category can be considered applicable to those AEs that, after careful medical consideration at the time they are evaluated, are considered to be unrelated to administration of the study drug(s).
Not related	Any event for which there is evidence that an alternative etiology exists or for which no timely relationship exists to the administration of the study drug(s) and the AE does not follow any previously documented pattern. This category applies to those AEs that, after careful medical consideration, are clearly and incontrovertibly due to causes other than the study drug(s).
Unclassifiable	There is insufficient information about the AE to allow an assessment of causality.

AE = adverse event; PI = principal investigator.