Patient-centered adverse event reporting in clinical trials: A novel approach using ECOG-ACRIN E2211.

Abstract

658 Background: The Common Terminology Criteria for Adverse Events (CTCAE) classifies adverse events (AEs) in clinical trials but traditionally limits the analysis to a single occurrence per patient and grade 3-4 AEs, overlooking frequent and lower grade AEs. We propose a new approach of AE reporting that captures both the safety profile and patient experience. Methods: We analyzed related AEs collected in the ECOG-ACRIN E2211 [Phase II capecitabine + temozolomide (Arm A) vs. temozolomide (Arm B) in advanced pancreatic neuroendocrine neoplasms] by CTCAE v4.0 and limited to hematologic and gastrointestinal (GI) categories for this exploratory analysis. We calculated AE burden, defined as the average occurrence of AE per patient experiencing the AE, measured by total occurrence of AEs, and divided by number of patients who developed the AE. We then compared burden of grade 3-4 AEs vs. grades 1-4 AEs. Sex differences were evaluated using t-tests. Results: For hematologic AEs, 72 patients reported 426 occurrences across grades 1-4 and 24 patients reported 39 occurrences for grades 3-4, resulting in AE burdens of 5.9 (grades 1-4) versus 1.6 (grades 3-4). For GI AEs, 108 patients reported 997 grade 1-4 events, and 13 patients reported 22 grade 3-4 events, resulting in AE burdens of 9.23 versus 1.69, respectively. Sex differences in AE burden are tabulated below (Table). For example, in Arm B, anemia burden was 4.8 (males) vs 2.7 (females) [p=0.068] for grades 1-4 and 0 (males) vs 1 (females) for grades 3 and 4. Conclusions: This AE reporting approach, accounting for the burden across grade 1-4, offers a different and more patient-centered assessment of AEs in clinical trials and may help better identify sex-based differences. Burden of AEs by treatment arm and sex distribution. Burden of Related AEs Categories of AEs Arm A (N=65) Arm B (N=68) Grade 1-Grade 4 Grade 3-Grade 4 Grade 1-Grade 4 Grade 3-Grade 4 Male Female p-value Male Female p-value Male Female p-value Male Female p-value Hematologic Anemia 2.9 3 0.937 0 0 4.8 2.7 0.068 0 1* Neutropenia 1.7 2.2 0.686 1 1* 1.2 2.3 0.064 1 1.1 0.356 Thrombocytopenia 4.3 2.6 0.241 1* 1.2 3.6 3.3 0.781 1 1 ** Gastrointestinal Abdominal pain 2.5 2.2 0.835 0 0 3.1 3 0.955 0 1* Constipation 4.1 3.2 0.515 1* 0 4.9 3.3 0.169 0 0 Diarrhea 1.8 3.6 0.158 0 0 2.6 2.5 0.940 1.25 1 0.390 Nausea 4.2 4.9 0.619 0 0 4.4 4.2 0.893 1 1** ** Vomiting 2.2 1.9 0.703 0 0 1.8 2.8 0.241 1 1 ** *Only 1 patient in each group **No variance within each group.