Profiles of research waste in randomized clinical trials comparing de-escalation and escalation strategies for breast cancer treatment.

Background: Cancer clinical trials produce a substantial amount of research waste. The relationship between different study types, such as de-escalation and escalation studies, and research waste has not been studied. Methods: This cross-sectional study reviewed phase 2, 3 and 4 randomized clinical trials of breast cancer therapy registered at ClinicalTrials.gov between 2011-2021. Research waste was defined as the presence of one or more of the following three features: nonpublication, inadequate reporting, and design limitations. Studies were categorized as de-escalation, escalation, or other treatment optimization studies, based on the interventions in the experimental and control groups. Results: In total, 240 studies were included, including 15 de-escalation studies, 139 escalation studies, and 86 other treatment-optimization studies. De-escalation studies were more likely to be non-pharmacological (26.7%), national (86.7%), or non-industry-funded (73.3%). Escalation studies were more likely to have a palliative intent (71.2%) and a double-blind design (42.4%). Heterogeneity among the three study types was observed across the three components of research waste as well as study discontinuation. Overall, 113 of the 240 studies (47.1%) demonstrated research waste. After adjusting for study characteristics such as design and discontinuation, escalation studies were independently associated with an increased risk of research waste compared to de-escalation studies (odds ratio, 4.337; 95% confidence interval, 1.165-18.567; P = 0.028). Conclusion: A substantial burden of research waste was observed among phase 2 to 4 breast cancer treatment studies. The burden of research waste varied across study types, highlighting the need for tailored strategies to mitigate waste. Given the limited number of de-escalation studies, these exploratory findings require further validation.