Abstract
PURPOSE: Currently, treatment-emergent adverse events (TEAEs) during a clinical study are summarized over the entire study period. OBJECTIVE: Develop and validate a novel methodology, BURDEN OF THERAPY(©∗) (BOTh(©∗)), to quantify presence and severity of TEAEs on each day of study. METHODS: BOTh utilizes patient-level safety data to derive a quantitative estimate for the burden of TEAEs that all or individual patients experience on each day of a clinical study. Burden estimate for each day is based on number and severity of TEAEs. A chart displays the total burden experienced by patients on each day throughout the study and statistical analyses may be performed with the area under curve. Methodology was applied to two validated and published clinical studies and statistically analyzed. RESULTS: In a peripheral neuropathic pain study, the topical group had a greater incidence of TEAEs than the oral anticonvulsant group when evaluated using current methodology. Utilizing BOTh, TEAEs with the topical agent were of short duration and occurred for three days after application, whereas TEAEs with the oral agent increased during dose titration and persisted to study end. In an overactive bladder study there was a minimal difference in overall TEAEs between groups, but BOTh revealed a higher burden related to dry mouth in the antimuscarinic versus β(3) adrenergic agonist group. CONCLUSIONS: BOTh is a highly sensitive method to evaluate the comparative burden experienced by patients during treatment, and can facilitate better informed treatment selection. We propose BOTh as the new standard for analyzing safety during clinical studies.