arXiv subjects

Letao Yuan

Publications and source records attributed to Letao Yuan.

2 recordsLinked to original sources

arXiv2026

Component over Composite: Mitigating Type I Error Inflation when Imputing "Days Alive and at Home"

Background: Days Alive and at Home (DAH) over a pre-defined follow-up period is a novel post-intervention composite outcome that combines data from at least three components: (i) initial length of hospital stay, (ii) length of total readmissions or other post-discharge care and (iii) mortality. Missing values bring unique challenges to the analysis of trials with the DAH outcome as the three components may have different rates of missingness caused by distinct missing data mechanisms. Current approaches define DAH as missing if any of the components are missing, and proceed with complete cases or Multiple Imputation (MI) of the composite. Methods: Through a simulation study motivated by the NOTACS trial, we compare several methods of handling missing data, including complete case analysis, MI of the composite, and MI of the components when the primary analysis is a Mann-Whitney-Wilcoxon test. Results: MI on the component level has good properties in terms of type I error control and power. We caution against the use of MI on the composite level with Predictive Mean Matching, which can lead to type I error inflation. Conclusions: Given the complex distributional characteristics of DAH, naive approaches such as defining missingness on the composite level and directly imputing the composite with Predictive Mean Matching, can lead to type I error inflation. Imputing on the component level is recommended, suggested future work included imputation approaches that are compatible with more complex definitions of DAH, as well as recommendations for sensitivity analyses to the Missing at Random assumption.

stat.ME↗

arXiv2026

Beyond the Composite: Enhancing Trial Analysis through a Divide & Conquer Approach to 'Days Alive and at Home': Insights from the NOTACS trial

"Days alive and at home" (DAH) is a recent patient-centered outcome measure for perioperative trials, defined as the number of days a patient spends at home during the follow-up period. DAH typically follows a zero-inflated, left-skewed, bi-modal distribution. Other increasingly used complex endpoints, such as days alive without a ventilator, share these statistical features arising from combining survival with another clinically relevant count outcome into a single, comprehensive measure. A key challenge for DAH and similar endpoints is the lack of a readily identifiable distributional form, which complicates the statistical design of trials using it as the primary endpoint, particularly regarding the robustness of sample size calculations and final analyses where the central limit theorem might not be suitable. Using 200 data points from the interim data of the NOTACS trial (ISRCTN14092678), whose primary endpoint was DAH, we developed a novel 'Divide & Conquer' model that breaks DAH into distinct parts modeled individually. To our knowledge, such a model has not been used before for DAH. We demonstrate that our approach significantly improves model fit compared to existing alternatives, enabling more suitable DAH data generation that can be used for simulation-based sample size calculations and evaluation of operating characteristics of the statistical test(s). Beyond NOTACS, our work has large potential to inform the design and analysis of other trials using DAH or similar complex endpoints.

stat.ME↗