Nearly half of the randomized breast cancer treatment trials in a registry review had at least one sign of research waste. The analysis classified waste as a trial that was never published, was inadequately reported, or had limitations in its design. That standard was met by 113 of 240 studies, or 47.1%.
The study focused on the trials themselves, asking how often they were published, adequately reported and designed without the specified limitations, and whether those problems varied by treatment strategy. Its main comparison was between de-escalation and escalation studies; other treatment-optimization studies were kept as a descriptive group.
A closer look at the trial set
It was a cross-sectional review of randomized controlled trials using publicly available ClinicalTrials.gov data. The search was conducted in 2025 and covered interventional breast cancer studies in phases 2, 3 and 4 that were registered from 2011 through 2021 and completed by 2022.
The final analysis included 240 studies involving 72,529 participants. Trial enrolment ranged from 2 to 4,804 participants, with a median of 163. The set included 15 de-escalation studies, 139 escalation studies and 86 other treatment-optimization studies.
In this classification, de-escalation meant reducing treatment intensity or components while aiming to maintain efficacy and safety. Escalation meant increasing intensity or adding components. The other group included trials testing dose schedules, treatment sequences, routes of administration or treatment modalities.
How the waste appeared
Of the 240 trials, 186, or 77.5%, were published in peer-reviewed journals. The median time from completion to publication was 21.5 months. The review counted 54 trials as unpublished.
Among published trials, 149 of 186, or 80.1%, were adequately reported. Yet 30 published trials, or 16.1%, had design limitations. Problems with the randomization process were the most common design issue, affecting 22 studies, or 11.8% of published trials.
Forty-five of 240 trials, or 18.8%, were discontinued prematurely, and the median difference between planned and actual enrolment was 90 participants. Poor recruitment accounted for 18 of those trials, or 40.0%; resource problems for eight, or 17.8%; and futility for seven, or 15.6%. Discontinuation was more common in trials with palliative intent than in those with curative intent, 23.3% versus 11.1%.
The patterns behind the numbers
When the researchers adjusted for multiple study features, premature discontinuation was associated with higher odds of research waste: the odds ratio was 9.227, with a 95% confidence interval from 3.639 to 23.398. An odds ratio compares the odds of an outcome between groups; a value above 1 indicates higher odds and a value below 1 lower odds in this comparison. Double-blind design was associated with lower odds, OR 0.399 (95% confidence interval 0.182 to 0.872), as was a large sample size, OR 0.192 (95% confidence interval 0.062 to 0.596). The intervals show the uncertainty around each estimate.
Those figures describe associations, not proof that stopping a trial caused waste or that blinding and larger samples prevented it. The review's cross-sectional design can show patterns in the records, but it cannot establish causation.
Escalation studies had higher premature-discontinuation rates than de-escalation studies, 21.6% versus 13.3%, and higher nonpublication, 24.5% versus 13.3%. After adjustment, escalation was associated with higher odds of waste than de-escalation, with an odds ratio of 4.337 and a 95% confidence interval from 1.165 to 18.567. The pattern was not consistent across every measure: inadequate reporting was numerically lower in escalation studies, 24.8% versus 30.8%, as were design deficiencies, 13.3% versus 15.4%.
The groups also differed in their design and funding profiles. Non-pharmacological interventions appeared in 26.7% of de-escalation studies and 1.4% of escalation studies; national recruitment in 86.7% and 40.3%; and non-industry funding in 73.3% and 20.1%. Escalation trials more often had palliative intent, 71.2% versus 40.0%, and double-blind designs, 42.4% versus 6.7%.
Why the comparison needs care
The uneven group sizes are a reason to read the comparison cautiously. Only 15 de-escalation studies were available, compared with 139 escalation studies and 86 other optimization studies. The review therefore reports a relationship within this ClinicalTrials.gov set, not evidence that one treatment strategy creates more or less waste. Its cross-sectional design means the estimates should be treated as associations.
Taken together, the findings describe a problem in the trial record rather than a verdict on treatment choices. Nearly half of the studies met at least one of the review's waste criteria, but the cross-sectional analysis cannot show whether study type or any other characteristic caused the waste.
Paper data and sources
Original title: Profiles of research waste in randomized clinical trials comparing de-escalation and escalation strategies for breast cancer treatment
Authors: Tang Y, Lin W, Li Z et al.
Journal/Repository: Frontiers in oncology
Status: Peer-reviewed
First online: 2026-10-09
DOI: Not available
Original paper · Full text