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Sangyoon Yi

Publications and source records attributed to Sangyoon Yi.

4 recordsLinked to original sources

Estimation of treatment effect in clinical trials of continuous endpoints with retrieved dropouts

The estimand framework provides guidance on handling intercurrent events, such as treatment discontinuation, in the analysis of clinical trial responses. Under ICH E9(R1), the treatment policy (TP) strategy incorporates post-discontinuation data to reflect treatment effects in real-world practice. However, many existing approaches focus primarily on imputing missing endpoint values for lost-to-follow-up subjects and do not explicitly model completers, retrieved dropouts (RDs), and lost-to-follow-up subjects within a unified framework. This may obscure the relationship between modeling assumptions and the estimand of interest when RD data are present. We propose a likelihood-based model for continuous endpoints that integrates data from all subject categories, including RDs. The approach combines an analysis of covariance formulation with a probit model for treatment discontinuation, enabling explicit formulation of treatment effects for estimands defined using the hypothetical and TP strategies. Estimation is carried out via a computationally efficient maximum likelihood procedure. Numerical studies demonstrate that the proposed method achieves improved bias and variability properties compared with commonly used imputation-based approaches.

stat.ME

Sensitivity Analysis for False Discovery Rate Estimation with Published p-Values

There is recent interest in estimating the false discovery rate (FDR) with published p-values. However, there is little formal research that addresses the manner and extent to which the presumed selection, or publication, bias model impacts the bias and variance of FDR estimators. This manuscript provides general and closed-form expressions for the bias and variance of an established FDR estimator when the publication bias model (p<0.05) may or may not be correct. Expressions reveal that FDR estimates could be conservative or liberal, depending on how well a $p<0.05$ publication rule approximates the true selection mechanism. Analysis of a well-studied large-scale replication project in psychology, where selection model parameters are estimable, suggests that bias expressions are accurate in practice. Another well-studied collection of p-values mined from medical journal abstracts is used to illustrate how provided closed-form expressions may facilitate a simple sensitivity analysis when the goal is FDR estimation using selected p-values with unknown selection mechanism.

stat.ME

CHIMA: a correlation-aware high-dimensional mediation analysis with its application to the living brain project study

Mediation analysis examines the pathways through which mediators transmit the effect of an exposure to an outcome. In high-dimensional settings, the joint significance test is commonly applied using variable screening followed by statistical inference. However, when mediators are highly correlated, existing methods may experience reduced statistical power due to inaccurate screening and residual bias in asymptotic inference. To address these issues, we propose CHIMA (Correlation-aware High-dimensional Mediation Analysis), an extension of a recently developed high-dimensional mediation analysis framework that enhances performance under correlation by integrating two advances: (i) high-dimensional ordinary least squares projection for accurate screening under correlation; and (ii) approximate orthogonalization for bias reduction. Simulation studies demonstrate that CHIMA effectively identifies active mediators even in the presence of strong correlations and outperforms competing methods across various settings. We further apply CHIMA to ribonucleic acid sequencing (RNA-seq) from the Living Brain Project, identifying genes that mediate the effect of Parkinson's disease on brain cell composition, thereby revealing cell-type-specific mechanisms of disease.

stat.ME

Hierarchical nuclear norm penalization for multi-view data

The prevalence of data collected on the same set of samples from multiple sources (i.e., multi-view data) has prompted significant development of data integration methods based on low-rank matrix factorizations. These methods decompose signal matrices from each view into the sum of shared and individual structures, which are further used for dimension reduction, exploratory analyses, and quantifying associations across views. However, existing methods have limitations in modeling partially-shared structures due to either too restrictive models, or restrictive identifiability conditions. To address these challenges, we formulate a new model for partially-shared signals based on grouping the views into so-called hierarchical levels. The proposed hierarchy leads us to introduce a new penalty, hierarchical nuclear norm (HNN), for signal estimation. In contrast to existing methods, HNN penalization avoids scores and loadings factorization of the signals and leads to a convex optimization problem, which we solve using a dual forward-backward algorithm. We propose a simple refitting procedure to adjust the penalization bias and develop an adapted version of bi-cross-validation for selecting tuning parameters. Extensive simulation studies and analysis of the genotype-tissue expression data demonstrate the advantages of our method over existing alternatives.

stat.ME