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Main Authors: Liu, Shanshan, Diao, Guoqing
Format: Preprint
Published: 2026
Subjects:
Online Access:https://arxiv.org/abs/2602.19220
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author Liu, Shanshan
Diao, Guoqing
author_facet Liu, Shanshan
Diao, Guoqing
contents Matched case-control studies are commonly employed in epidemiological research for their convenience and efficiency. Analysis of secondary outcomes can yield valuable insights into biological pathways and help identify genetic variants of importance. Naive analysis using standard statistical methods, such as least-squares regression for quantitative traits, can be misleading because they fail to account for unequal sampling induced by the case-control design and matching. In this paper, we propose novel statistical methods that appropriately reflect the study design and sampling scheme in the analysis of secondary outcome data. The new methods provide consistent estimation and accurate coverage probabilities for the confidence interval estimators. We demonstrate the advantages of the new methods through simulation studies and a real application with diabetes patients. R code implementing the proposed methods is publicly available.
format Preprint
id arxiv_https___arxiv_org_abs_2602_19220
institution arXiv
publishDate 2026
record_format arxiv
spellingShingle A likelihood approach to proper analysis of secondary outcomes in matched case-control studies
Liu, Shanshan
Diao, Guoqing
Methodology
Matched case-control studies are commonly employed in epidemiological research for their convenience and efficiency. Analysis of secondary outcomes can yield valuable insights into biological pathways and help identify genetic variants of importance. Naive analysis using standard statistical methods, such as least-squares regression for quantitative traits, can be misleading because they fail to account for unequal sampling induced by the case-control design and matching. In this paper, we propose novel statistical methods that appropriately reflect the study design and sampling scheme in the analysis of secondary outcome data. The new methods provide consistent estimation and accurate coverage probabilities for the confidence interval estimators. We demonstrate the advantages of the new methods through simulation studies and a real application with diabetes patients. R code implementing the proposed methods is publicly available.
title A likelihood approach to proper analysis of secondary outcomes in matched case-control studies
topic Methodology
url https://arxiv.org/abs/2602.19220