Incomplete Toxicity Reporting and Use of Toxicity-Minimizing Language in Phase III Oncology Trials.

Abstract

Purpose: This study aimed to determine complete toxicity reporting (CTR), and the use of subjective toxicity-minimizing language (TML) among phase III oncology trials.

Methods: Two-arm superiority-design phase III oncology trials published from 2002 to 2020 were reviewed for toxicity data. CTR was defined as reporting total adverse events (TAEs), total serious adverse events (SAEs), total deaths, and study therapy discontinuations because of toxicity. Guideline concordance was defined according to guidelines published in the BMJ (defined as reporting total SAEs, total deaths, and study therapy discontinuations because of toxicity). TML was defined as a set of terms that subjectively downplay the harm of therapies.

Results: A total of 407 trials enrolling 322,645 patients were included. Most (51%, n = 207) reported SAEs, 88% (n = 358) reported total deaths, and 84% (n = 340) reported study therapy discontinuation because of toxicity. Although 55% of trials (n = 223) reported TAEs, only 32% (n = 131; 95% credible interval, 28 to 37) fit the criteria for CTR. CTR was more common in trials with industry sponsorship (37%) than with cooperative group sponsorship (4%). All 131 trials where CTR was observed were industry-sponsored, and only 3% (4/131) were cooperative group-sponsored trials. TML was used in 46% of trials (n = 186; 95% credible interval, 41 to 51), with no trial-related factors (including sponsorship source) associated with the odds of TML use.

Conclusion: Toxicity in phase III oncology clinical trials is often incompletely reported and is frequently minimized in its interpretation. Industry-sponsored trials more comprehensively report toxicity than do cooperative group-sponsored trials. CTR may improve patients' and oncologists' understanding of new treatments; thus, a more standardized approach to reporting toxicity data is needed.