Research in context
Evidence before this study
Conventional reporting of toxic effects in cancer trials is inadequate in the era of chronically administered, novel cancer treatments. The traditional maximum grade approach to reporting toxic effects does not depict onset, duration, or trajectory of adverse events, nor does it address longer lasting, lower grade toxic effects that might occur at substantial expense to a patient's quality of life. A narrow focus on high-grade toxic effects is insufficient and potentially misleading.
Longitudinal and graphical methods of assessing adverse events exist, but to our knowledge, there have not been any clinically focused efforts specifically aimed at modernising the approach to adverse event evaluation to better show the side-effects of newer, chronic treatments for cancer. We aimed to challenge conventional methods of adverse event reporting and present a novel approach to toxicity analysis that assesses adverse events over time.
Added value of this study
Using adverse event data from two completed trials, our findings show that the Toxicity over Time (ToxT) method can be used to construct clinically meaningful statistical summaries of adverse event data over time. The various outputs recorded in the ToxT analysis uncover clinically relevant information such as time to onset of adverse events and the potential to identify subpopulations of patients with atypical adverse event responses.
Implications of all the available evidence
Our study demonstrates a practical application of a new, longitudinal approach to adverse event analysis. An improved, clinically oriented, longitudinal approach adverse event analysis fulfils an important and unmet need in oncology. ToxT has a role in the clinic, for optimally counselling individual patients on the anticipated side-effects of a given treatment, and in clinical trials, to better depict adverse events of novel agents or combinations, and to make trials more patient-centred. This type of information might also be central to the process of securing regulatory approval for novel agents in the future.