Title : Research waste in ewing sarcoma: Predictors of clinical trial discontinuation and nonpublication
Abstract:
Background: Ewing sarcoma is a rare primary bone and soft tissue malignancy encountered in orthopaedic oncology, where high-quality clinical evidence is essential for guiding treatment. Premature trial discontinuation and nonpublication reduce the available evidence and contribute to research waste. This study evaluated the prevalence and predictors of these outcomes in registered Ewing sarcoma clinical trials.
Methods: A cross-sectional analysis was conducted using interventional Ewing sarcoma trials registered on ClinicalTrials.gov between January 1999 and March 2025. Trial characteristics including study phase, funding source, enrolment size, intervention type, masking, and study design were extracted. Publication status was determined through ClinicalTrials.gov together with PubMed and Google Scholar searches. Multivariable logistic regression identified predictors of trial discontinuation and nonpublication.
Results: A total of 181 eligible trials were included. Of these, 141 (77.9%) were completed, while 40 (22.1%) were discontinued. Only 33 completed trials (23.4%) were subsequently published. Trials enrolling fewer than 100 participants demonstrated significantly higher discontinuation rates than larger studies (26.2% vs. 7.4%, p=0.028) and were substantially more likely to remain unpublished (86.1% vs. 51.9%, p=0.002). NIH-funded trials had significantly lower odds of discontinuation than industry-funded studies (adjusted OR 0.12, 95% CI 0.02–0.71). Multicentre studies were independently associated with a lower likelihood of nonpublication (adjusted OR 0.15, 95% CI 0.05–0.46), while enrolment of at least 100 participants was also protective against nonpublication (adjusted OR 0.30, 95% CI 0.11–0.81).
Conclusions: Clinical trials in Ewing sarcoma experience substantial rates of discontinuation and nonpublication. Small enrolment and single-centre study design are major contributors to unsuccessful trial completion and dissemination. Strengthening multicentre collaboration, improving recruitment strategies, and ensuring timely reporting of all trial outcomes may reduce research waste and improve the evidence base for this rare orthopaedic malignancy.
