In oncology clinical trials , traditional Adverse Event (AE) reporting of maximum grades ignores the time profile (onset and duration) or the co-occurrence of AEs.
Burden of therapy (BOTh; Abdullah et al, CCT 2016) is a graphical and analytical approach to summarize the daily individual patient toxicity burden based on number, duration and severity of AEs. BOTh can be charted over time, overall and by treatment arm. We applied BOTh to treatment-emergent AE (TEAE) data from the EORTC Brain tumour group trial: EORTC26101 (NCT01290939) assessing the addition of bevacizumab to lomustine at first progression of glioblastoma (Wick et al, NEJM 2017).
A total of 2643 TEAE events were reported in 430 patients who started their allocated treatment. Compared to traditional AE reporting, BOTh showed the additional longlasting burden of grade 3-4 events in the combination arm. Analysis can be limited to specific AE terms and/or subgroups. However displaying burden weighted by AE grade disproportionally overemphasized high grades visually. Fatal adverse events required specific coding to ensure adequate representation.
BOTh is a feasible method to evaluate complete AE burden over time. These longitudinal comprehensive analyses are relevant to clinicians and patients in cancer clinical trials.
Corneel Coens is currently working as a lead statistician at the EORTC Headquarters (Brussels, Belgium). As part of his tasks for the EORTC Quality of Life Department, he is involved in various aspects of Quality of Life in many oncological clinical trials ranging from instrument validation to design, analysis and reporting of QoL endpoints. He is also the designated study statistician for the EORTC Gynaecological Cancer Group since 2001. He is a regular contributor for various EORTC educational courses such as “Clinical Trial Statistics for Non-Statisticians” and is course director for the Joint FECS/AACR/ASCO Workshop “Methods in Clinical Cancer Research”.