US Food and Drug Administration Analysis of Patient-Reported Diarrhea and Its Impact on Function and Quality of Life in Patients Receiving Treatment for Breast Cancer

•Many trials report “no meaningful difference” in health-related quality of life (HRQL) or function between arms despite observing notable differential toxicity. A possible explanation is that mean change from baseline analyses of function or HRQL can obscure important change in subgroups experiencing symptomatic toxicity.•In our case examples, for those patients who remained on treatment and completed patient-reported outcome assessments, there was a greater proportion of patients in the treatment arm reporting diarrhea. Patients reporting more frequent diarrhea reported lower physical functioning and global health status and quality of life than patients with no diarrhea, regardless of treatment arm.•When differential toxicity between arms is observed, additional exploratory analyses aided by data visualization that evaluate functioning or HRQL by symptomatic adverse event are needed. This information can further inform the safety and tolerability of the investigational agent under study.