Background The National Clinical Trials Network (NCTN) is the largest government sponsored organization in the United States tasked with funding randomized controlled trials (RCTs) in oncology. It is unknown whether there are differences in study design by treatment modality. We evaluated differences in methodology between trials testing radiotherapy versus systemic therapy. Methods The Clinical Trials Support Unit website was used to identify active RCTs of systemic or radiotherapy across NCTN cooperative groups through December 31, 2023. Studies in disease sites with > 5 radiotherapy trials were included. Each trial’s protocol was reviewed to obtain key design information that were descriptively compared: primary endpoint, hypothesis testing type (superiority vs non-inferiority), non-inferiority margin, hypothesized effect size, power, and significance level. Results A total of 186 RCTs (142 systemic therapy, 44 radiotherapy) were examined. Comparing primary endpoints, 59.1% vs 26.8% of radiotherapy vs systemic therapy trials, respectively, had a primary endpoint of overall survival. Nearly 1/3 of radiotherapy trials (31.2%) were non-inferiority vs 6.3% of systemic therapy trials. Among breast cancer trials, 75% of radiotherapy studies were non-inferiority vs 11.1% systemic. Target effect size, power, and significance level were similar by treatment modality within tumor types and disease settings. Conclusion Among NCTN cooperative group RCTs, there were marked differences in study design between radiotherapy vs systemic therapy trials. A higher benchmark for defining success for radiotherapy interventions was observed with greater emphasis on overall survival as primary endpoint. This may reflect differences in therapeutic mechanism by modality and types of study questions posed.

中文翻译：

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放疗与全身治疗成功的基准美国国家临床试验网络 （NCTN） 由美国国家癌症研究所 （NCI） 赞助的随机对照试验


背景 美国国家临床试验网络 （NCTN） 是美国最大的政府资助组织，负责资助肿瘤学随机对照试验 （RCT）。目前尚不清楚不同治疗方式的研究设计是否存在差异。我们评估了测试放疗与全身治疗的试验之间的方法学差异。方法 临床试验支持单位网站用于确定截至 2023 年 12 月 31 日的 NCTN 合作小组中全身或放疗的活跃 RCT。纳入了 > 5 项放疗试验的疾病部位的研究。审查每项试验的方案以获得关键设计信息，并进行描述性比较：主要终点、假设检验类型 （优效性与非劣效性）、非劣效性边际、假设效应大小、功效和显着性水平。结果 共检查了 186 篇 RCT （142 篇全身治疗，44 篇放疗）。比较主要终点，放疗与全身治疗试验的主要终点分别为 59.1% 和 26.8%，主要终点为总生存期。近 1/3 的放疗试验 （31.2%） 是非劣效性的，而全身治疗试验的 6.3% 是非劣效性的。在乳腺癌试验中，75% 的放疗研究是非劣效性的，而 11.1% 是全身性的。肿瘤类型和疾病环境中的治疗方式的靶效应大小、功效和显着性水平相似。结论 在 NCTN 合作组 RCT 中，放疗与全身治疗试验的研究设计存在显著差异。观察到定义放疗干预成功的更高基准，更加强调总生存期作为主要终点。 这可能反映了治疗机制因方式和所提出的研究问题类型而异。