Table 1.

Classification of Adverse Events and Their Relationship to Ferumoxytol Administration

A. Classification of Adverse Events (AE)a
Severity	Definition
Mild (grade 1)	Experience resulting in transient or mild discomfort; no limitation in activity; no medical intervention or therapy required. The patient may be aware of the sign or symptom but tolerates it reasonably well.
Moderate (grade 2)	Experience resulting in mild to moderate limitation in age‐appropriate instrumental activity of daily living (ADLs)b; noninvasive or minimal medical intervention/therapy required.
Severe (grade 3)	Experience resulting in marked limitation in age‐appropriate self‐care ADLsb but not life‐threatening, medical intervention/therapy required, hospitalizations or prolongation of hospitalizations possible.
Life‐threatening (grade 4)	Experience resulting in risk of death due to the adverse experience as it occurred; urgent intervention required.
Fatal (grade 5)	Experience resulting in death related to AE, persistent or significant disability/incapacity, and congenital anomaly/birth defect.
B. Relationship of AE to Ferumoxytol Administration
Classification	Definition
Definitely	Previously known toxicity of agent; or an event that follows a reasonable temporal sequence from administration of the drug; that follows a known or expected response pattern to the suspected drug; that is confirmed by stopping or reducing the dosage of the drug; and that is not explained by any other reasonable hypothesis.
Probably	An event that follows a reasonable temporal sequence from administration of the drug; that follows a known or expected response pattern to the suspected drug; that is confirmed by stopping or reducing the dosage of the drug; and that is unlikely to be explained by the known characteristics of the subject's clinical state or by other interventions.
Possibly	An event that follows a reasonable temporal sequence from administration of the drug; that follows a known or expected response pattern to that suspected drug; but that could readily have been produced by a number of other factors.
Unrelated	An event that can be determined with certainty to have no relationship to the study drug.

^aBased on the Common Terminology Criteria for Adverse Events (CTCAE) v4.0 developed by the National Cancer Institute(22). Adverse events (AE) are defined as any unfavorable and unintended signs, symptoms, or disease temporally associated' with the administration of ferumoxytol regardless of the causal relationship.

^bActivities of daily living (ADLs). Definitions are as defined in CTCAE v4.0: Instrumental ADLs refer to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc. Self‐care ADLs refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden.