Evaluating Treatment Tolerability Using the Toxicity Index With Patient-Reported Outcomes Data.

ABSTRACT

CONTEXT Summarizing longitudinal symptomatic adverse events during clinical trials is necessary for understanding treatment tolerability. The Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) provides insight for capturing treatment tolerability within trials. Tolerability summary measures, such as the maximum score, are often used to communicate the potential negative symptoms both in the medical literature and directly to patients. Commonly, the proportions of present and severe symptomatic adverse events are used and reported between treatment arms among adverse event types. The toxicity index is also a summary measure previously applied to clinician-reported CTCAE data. OBJECTIVES: Apply the toxicity index to PRO-CTCAE data from the COMET-2 trial alongside the maximum score, then present and discuss considerations for using the toxicity index as a summary measure for communicating tolerability to patients and clinicians. METHODS: Proportions of maximum PRO-CTCAE severity levels and median toxicity index were computed by arm using all trial data and adjusting for baseline symptoms. RESULTS: Group-wise statistical differences were similar whether using severity level proportions or the toxicity index. The impact of adjusting for baseline symptoms was equivalently seen when comparing arms using severity rates or the toxicity index. CONCLUSION: The toxicity index is a useful method when ranking patients from those with the least to most symptomatic adverse event burden. This study showed the toxicity index can be applied to PRO-CTCAE data. Though as a tolerability summary measure, further study is needed to provide a clear clinical or patient-facing interpretation of the toxicity index.