Analysis of adverse events attribution and reporting in cancer clinical trials: A systematic review. (April 2021)

• Record Type: Journal Article
• Authors: Enrico, Diego; Waisberg, Federico; Burton, Jeannette; Mandó, Pablo; Chacón, Matías
• Is Part Of: Critical reviews in oncology/hematology. Volume 160(2021)
• Publication Date: 2021-04
• Subjects: Attribution -- Adverse event -- Clinical trial -- Placebo -- Cancer treatment -- Toxicity; Oncology -- Periodicals; Hematology -- Periodicals; 616.994
• DOI: 10.1016/j.critrevonc.2021.103296
• Languages: English
• ISSNs: 1040-8428

Abstract

Graphical abstract: Highlights: Drug safety investigation is crucial in cancer clinical trials. We reviewed adverse events (AEs) reporting and attribution process in oncology trials. Among 60 manuscripts analyzed, the majority (66.6 %) presented an incomplete report of AEs attribution. One-third of the studies did not specify the total frequency of all-grade and grade 3−4 AEs. Half of the patients suffering from AEs in the placebo arms were misattributed to an inert substance. Abstract: We systematically reviewed the quality of AEs reports in published oncology trials analyzing also the bias in the attribution process. We searched MEDLINE, PubMed (2000–2019) selecting randomized, double-blind, placebo-controlled, and phase 3 cancer trials using exclusively targeted therapy or immunotherapy-related drugs. The proportion of publications with complete AE reports (including both all-cause and drug-related AE data) and the AEs attribution ratio (patients with drug-related over all-cause AE) were investigated. Among 60 trials (38, 174 patients) included, 40 (66.6 %) presented an incomplete report of AEs attribution. Journals with the lowest impact factor were significantly associated with deficient reports of grade 3−4 AEs (p = 0.02). Under placebo administration, the median incidence of all-grade drug-related AEs was 49 % (IQR 39–56). The median attribution ratio for all-grade AEs in the active and placebo arms was 88.9 % (IQR 79.8–93) and 53.9 % (IQR 43.4–60.9), respectively. The AEs reporting and attribution process appear to be more unreliable than expected.