Patient-Reported Outcomes to Inform Tolerability Characterization in Cancer Trials: A Critical Perspective on Unresolved Methodological Issues

Patient-reported outcomes assessing treatment toxicity and its impact, and aspects of quality of life, have become increasingly important components of oncology drug development including early phase dose optimization studies. Despite insights from these data, there are limitations on drawing inferences about whether a treatment is tolerable or intolerable, which requires understanding individual risk-benefit assessments that vary between patients, cancer types, and stages of disease. This commentary examines unresolved methodological issues requiring more research rigor and attention: the development of tolerability thresholds based upon toxicity severity data; the direct measurement of tolerability through specific patient self-report measures; and overcoming the challenge of baseline value assessment in important measures such as single item side-effect bother assessments. We call for further research to resolve these challenges and drive more robust inference-making from patient-reported outcomes data collected in cancer clinical trials.