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

Abstract

Introduction

Randomized controlled trials (RCTs) are designed to provide the highest levels of evidence for clinical practice; consequently, RCTs are the mainstay for creating guidelines and approving new treatments. It is ethically essential for patients assigned to the control arm in RCTs to receive standard-of-care treatment. This serves to protect patients, optimize adequate treatment, and ensures that RCT findings are compared to current standard-of-care therapy – an ethical imperative of RCT design and implementation. Oncologic medical trials investigating new systemic agents for cancer have a high proportion of RCTs with inadequate control arms (PMID 31046071). It is unknown whether this finding is prevalent in oncologic trials investigating radiation therapy (RT) for cancer.

Methods

We identified registered clinical trials investigating RT in patients with cancer over the past decade. ClinicalTrials.gov was queried for RT as the intervention and cancer and other related terms as the condition between 1/1/13 and 1/1/23. Exclusion criteria included trials with incomplete status or non-oncologic indications. Trials were categorized by indication/primary disease site, first posted date, investigational arm, control arm, and sponsor/collaborator. Each control arm was analyzed, and the standard of care was determined according to National Comprehensive Cancer Center Network (NCCN) guidelines at the time of first posting.

Results

A total of 508 interventional studies with results registered on ClinicalTrials.gov were included. Of these, 360 single-arm studies were excluded. 116 studies investigating a treatment other than RT were excluded. 20 studies that were not completed were excluded. The remaining 12 studies were included in the final analysis. Of the included trials, 2 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. A majority of the trials were industry-funded (83%), and over 2/3 of studies took place in the United States (75%). 100% of the trials were found to have an adequate control arm per the corresponding NCCN.

Conclusion

100% of oncologic RCTs investigating radiation therapy for cancer were found to have an adequate control arm. This finding contrasts with medical oncology trials, which have been shown to have a high proportion of RCTs with inadequate control arms. This disparity highlights the importance of designing oncologic RCTs with adequate control arms, which is crucial for providing the highest level of evidence to guide optimal clinical practice and ensure the safety of patients. 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.