Robust Permutation Test of Intraclass Correlation Coefficient for Assessing Agreement

Background: Inter-rater reliability is critical in oncology to ensure consistent and reliable measurements across raters and methods, such as when evaluating biomarker levels in different laboratories or comparing tumor size assessments by radiation oncologists during therapy planning. This consistency is essential for informed decision-making in both clinical and research contexts, and the intraclass correlation coefficient (ICC) is a widely recommended statistic for assessing agreement. This work focuses on hypothesis testing of the ICC(2,1) with two raters. Methods: We evaluated the performance of a naive permutation test for testing the hypothesis H0:ICC=0 and found that it fails to reliably control the type I error rate. To address this, we developed a robust permutation test based on a studentized statistic, which we prove to be asymptotically valid even when paired variables are uncorrelated but dependent. Results: Simulation studies demonstrate that the proposed test consistently maintains type I error control, even with small sample sizes, outperforming the naive approach across various data-generating scenarios. Conclusions: The proposed studentized permutation test for ICC(2,1) offers a statistically valid and robust method for assessing inter-rater reliability and demonstrates practical utility when applied to two real-world oncology datasets.