Evaluation of Control Arm Quality in Recent Radiation Oncology Randomized Clinical Trials.

Abstract

Background: For randomized controlled trials (RCTs) to provide the highest levels of evidence for clinical practice, it is ethically imperative for patients assigned to the control arm to receive standard-of-care treatment. Oncologic medical trials investigating new systemic agents have demonstrated a high proportion of RCTs with inadequate control arms. It is unknown whether this finding is prevalent in oncologic trials investigating radiation therapy (RT) for cancer.

Methods: ClinicalTrials.gov was queried for registered clinical trials investigating RT in patients with cancer from 2013 to 2023. Each control arm was analyzed, with the standard of care determined by National Comprehensive Cancer Center Network (NCCN) guidelines at the time of initial trial posting.

Results: Five hundred eight interventional studies with results registered were included, of which 12 met inclusion criteria for final analysis. Two trials each investigated RT usage in central nervous system, prostate, head and neck, and breast disease sites, and 1 each for lung, hepatobiliary, rectal, and bone disease sites. Most trials were industry-funded (83%); 75% of studies took place in the United States. Hundred percent of trials had an adequate control arm per the corresponding NCCN guidelines.

Conclusion: All recently completed oncologic RCTs investigating RT for cancer involved an adequate control arm. This finding contrasts with the high proportion of inadequate control arms in medical oncology trials. These findings suggest that adequate control arm treatments are feasible to achieve in trial design, emphasizing both the need for continued focus on improving the quality of ethical oncologic research trials and a possible subspecialty that may serve as an exemplar.