Adverse Event Burden Score—A Versatile Summary Measure for Cancer Clinical Trials

SIMPLE SUMMARY: In cancer clinical trials, adverse event data are collected after every treatment cycle, using the Common Terminology Criteria for adverse events, which includes 837 terms. The vast number of potentially reportable adverse events over multiple treatment cycles makes summarizing and analyzing adverse event data challenging. The current standard reporting of adverse event data includes the frequency of the maximum (worst) grade of commonly occurring adverse events. In this article, we propose a single quantitative summary measure that incorporates both the frequency and the severity of multiple adverse events over time; the adverse event burden score. This score is a well-defined measure that enables statistical comparisons analogous to other quantitative endpoints in clinical trials. The adverse event burden score can readily accommodate different trial settings, diseases, and treatments, with diverse safety profiles. ABSTRACT: This article introduces the adverse event (AE) burden score. The AE burden by treatment cycle is a weighted sum of all grades and AEs that the patient experienced in a cycle. The overall AE burden score is the total AE burden the patient experienced across all treatment cycles. AE data from two completed Alliance multi-center randomized double-blind placebo-controlled trials, with different AE profiles (NCCTG 97-24-51: 176 patients, and A091105: 83 patients), were utilized for illustration. Results of the AE burden score analyses corroborated the trials’ primary results. In 97-24-51, the overall AE burden for patients on the treatment arm was 2.2 points higher than those on the placebo arm, with a higher AE burden for patients who went off treatment early due to AE. Similarly, in A091105, the overall AE burden was 1.6 points higher on the treatment arm. On the placebo arms, the AE burden in 97-24-51 remained constant over time; and increased in later cycles in A091105, likely attributable to the increase in disease morbidity. The AE burden score enables statistical comparisons analogous to other quantitative endpoints in clinical trials, and can readily accommodate different trial settings, diseases, and treatments, with diverse AE profiles.