Table 2 Differences in the Reporting Format of AEs (including irSAEs) between Published RCTs and Trial Results posted on ClinicalTrials.gov

Causality

Establishing drug-causality for AEs

Primarily report treatment-related AEs (trAEs)

All-cause AEs are reported regardless of drug causality

Structural hierarchy

The level at which different types of AE are reported

System Organ Class (SOC) and / or Preferred Terms (PTs) according to MedDRA are used

e.g., SOC: higher level group term (e.g., skin, GI)

PT: lower level group term (e.g., rash, colitis)

Report AE occurrence using PTs, but typically not by SOCs

Severity or grade

The intensity of an AE (mild, moderate, severe, etc.)

Often report AE grades; choice of presentation grading categories varies.

e.g., some publications report grade 3–4 combined, others report grades 3, 4 and 5 together.

Grading is most often not reported in trial registry results

Incidence of various types of AE

Reporting the number of patients or events

Generally report the number of AEs

e.g., number of events which included rashes (including all grades and multiple episodes in patients, unless explicitly indicated that the highest grade per patient is reported)

Usually report the number of patients who experienced each specific type of AE

e.g., number of patients in treatment arm 1 who experienced serious autoimmune colitis

Frequency threshold

The incidence of AEs occurring beyond a certain threshold

Authors often choose a higher frequency threshold to report AEs in the main text, however, they may choose to report a more comprehensive list using a lower cutoff in the supplementary tables

e.g., 10% in the main table and 1% in the supplement

ClinicalTrials.gov requires investigators to report all SAEs, and events ≥5% for non-SAEs