Justification, Margin Values, and Analysis Populations for Oncologic Noninferiority and Equivalence Trials: a Meta-Epidemiological Study

Troy J Kleber,Alexander D Sherry, Andrew J Arifin,Gabrielle S Kupferman,Ramez Kouzy,Joseph Abi Jaoude,Timothy A Lin,Esther J Beck,Avital M Miller,Adina H Passy,Zachary R McCaw,Pavlos Msaouel,Ethan B Ludmir

Journal of the National Cancer Institute（2025）

Department of Radiation Oncology | Insitro

Cited 0|Views2

Abstract

BACKGROUND:Noninferiority and equivalence trials evaluate whether an experimental therapy's effect on the primary endpoint is contained within an acceptable margin compared with standard of care. The reliability and impact of this conclusion, however, is largely dependent on the justification for this design, the choice of margin, and the analysis population used. METHODS:A meta-epidemiological study was performed of phase 3 randomized noninferiority and equivalence oncologic trials registered at ClinicalTrials.gov. Data were extracted from each trial's registration page and primary manuscript. RESULTS:We identified 65 noninferiority and 10 equivalence trials that collectively enrolled 61 632 patients. Of these, 61 (81%) trials demonstrated noninferiority or equivalence. A total of 65 (87%) trials were justified in the use of a noninferiority or equivalence design either because of an inherent advantage (53 trials), a statistically significant quality-of-life improvement (6 trials), or a statistically significant toxicity improvement (6 trials) of the interventional treatment relative to the control arm. Additionally, 69 (92.0%) trials reported a prespecified noninferiority or equivalence margin of which only 23 (33.3%) provided justification for this margin based on prior literature. For trials with time-to-event primary endpoints, the median noninferiority margin was a hazard ratio of 1.22 (range = 1.08-1.52). Investigators reported a per-protocol analysis for the primary endpoint in only 28 (37%) trials. CONCLUSIONS:Although most published noninferiority and equivalence trials have clear justification for their design, few provide rationale for the chosen margin or report a per-protocol analysis. These findings underscore the need for rigorous standards in trial design and reporting.

Translated text

求助PDF

上传PDF

Bibtex

AI Read Science

AI Summary

AI Summary is the key point extracted automatically understanding the full text of the paper, including the background, methods, results, conclusions, icons and other key content, so that you can get the outline of the paper at a glance.

Example

Background

Key content

Introduction

Methods

Results

Related work

Fund

Key content

Pretraining has recently greatly promoted the development of natural language processing (NLP)
We show that M6 outperforms the baselines in multimodal downstream tasks, and the large M6 with 10 parameters can reach a better performance
We propose a method called M6 that is able to process information of multiple modalities and perform both single-modal and cross-modal understanding and generation
The model is scaled to large model with 10 billion parameters with sophisticated deployment, and the 10 -parameter M6-large is the largest pretrained model in Chinese
Experimental results show that our proposed M6 outperforms the baseline in a number of downstream tasks concerning both single modality and multiple modalities We will continue the pretraining of extremely large models by increasing data to explore the limit of its performance

Upload PDF to Generate Summary

Must-Reading Tree

Example

Generate MRT to find the research sequence of this paper

Data Disclaimer

The page data are from open Internet sources, cooperative publishers and automatic analysis results through AI technology. We do not make any commitments and guarantees for the validity, accuracy, correctness, reliability, completeness and timeliness of the page data. If you have any questions, please contact us by email: report@aminer.cn

Chat Paper

【要点】：本研究通过元流行病学研究分析了肿瘤学非劣效性和等效性试验的合理性、边缘值选择和分析人群，发现大多数试验设计合理，但很少有试验提供了边缘值选择的理由或报告了按协议分析结果。

【方法】：研究采用元流行病学方法，对在ClinicalTrials.gov注册的3期随机非劣效性和等效性肿瘤学试验进行了分析，数据来源于试验注册页和主要手稿。

【实验】：共识别了65项非劣效性试验和10项等效性试验，涉及61,632名患者，其中81%的试验显示出非劣效性或等效性，92%的试验报告了预设的非劣效性或等效性边缘值，但仅有33.3%的试验提供了基于先前文献的边缘值选择理由。对于时间至事件主要终点（PEP），中位非劣效性边缘值为风险比1.22（范围，1.08-1.52），仅有37%的试验报告了按协议分析结果。