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Abstract In this study, we focus on estimating the heterogeneous treatment effect (HTE) for survival outcome. The outcome is subject to censoring and the number of covariates is high-dimensional. We utilize data from both the randomized controlled trial (RCT), considered as the gold standard, and real-world data (RWD), possibly affected by hidden confounding factors. To achieve a more efficient HTE estimate, such integrative analysis requires great insight into the data generation mechanism, particularly the accurate characterization of unmeasured confounding effects/bias. With this aim, we propose a penalized-regression-based integrative approach that allows for the simultaneous estimation of parameters, selection of variables, and identification of the existence of unmeasured confounding effects. The consistency, asymptotic normality, and efficiency gains are rigorously established for the proposed estimate. Finally, we apply the proposed method to estimate the HTE of lobar/sublobar resection on the survival of lung cancer patients. The RCT is a multicenter non-inferiority randomized phase 3 trial, and the RWD comes from a clinical oncology cancer registry in the United States. The analysis reveals that the unmeasured confounding exists and the integrative approach does enhance the efficiency for the HTE estimation. 

Abstract Rejective sampling improves design and estimation efficiency of single-phase sampling when auxiliary information in a finite population is available. When such auxiliary information is unavailable, we propose to use two-phase rejective sampling (TPRS), which involves measuring auxiliary variables for the sample of units in the first phase, followed by the implementation of rejective sampling for the outcome in the second phase. We explore the asymptotic design properties of double expansion and regression estimators under TPRS. We show that TPRS enhances the efficiency of the double-expansion estimator, rendering it comparable to a regression estimator. We further refine the design to accommodate varying importance of covariates and extend it to multi-phase sampling. We start with the theory for the population mean and then extend the theory to parameters defined by general estimating equations. Our asymptotic results for TPRS immediately cover the existing single-phase rejective sampling, under which the asymptotic theory has not been fully established. 

Summary Functional principal component analysis has been shown to be invaluable for revealing variation modes of longitudinal outcomes, which serve as important building blocks for forecasting and model building. Decades of research have advanced methods for functional principal component analysis, often assuming independence between the observation times and longitudinal outcomes. Yet such assumptions are fragile in real-world settings where observation times may be driven by outcome-related processes. Rather than ignoring the informative observation time process, we explicitly model the observational times by a general counting process dependent on time-varying prognostic factors. Identification of the mean, covariance function and functional principal components ensues via inverse intensity weighting. We propose using weighted penalized splines for estimation and establish consistency and convergence rates for the weighted estimators. Simulation studies demonstrate that the proposed estimators are substantially more accurate than the existing ones in the presence of a correlation between the observation time process and the longitudinal outcome process. We further examine the finite-sample performance of the proposed method using the Acute Infection and Early Disease Research Program study. 

ABSTRACT Many trials are designed to collect outcomes at or around pre-specified times after randomization. If there is variability in the times when participants are actually assessed, this can pose a challenge to learning the effect of treatment, since not all participants have outcome assessments at the times of interest. Furthermore, observed outcome values may not be representative of all participants’ outcomes at a given time. Methods have been developed that account for some types of such irregular and informative assessment times; however, since these methods rely on untestable assumptions, sensitivity analyses are needed. We develop a sensitivity analysis methodology that is benchmarked at the explainable assessment (EA) assumption, under which assessment and outcomes at each time are related only through data collected prior to that time. Our method uses an exponential tilting assumption, governed by a sensitivity analysis parameter, that posits deviations from the EA assumption. Our inferential strategy is based on a new influence function-based, augmented inverse intensity-weighted estimator. Our approach allows for flexible semiparametric modeling of the observed data, which is separated from specification of the sensitivity parameter. We apply our method to a randomized trial of low-income individuals with uncontrolled asthma, and we illustrate implementation of our estimation procedure in detail. 

Longitudinal clinical trials for which recurrent events endpoints are of interest are commonly subject to missing event data. Primary analyses in such trials are often performed assuming events are missing at random, and sensitivity analyses are necessary to assess robustness of primary analysis conclusions to missing data assumptions. Control‐based imputation is an attractive approach in superiority trials for imposing conservative assumptions on how data may be missing not at random. A popular approach to implementing control‐based assumptions for recurrent events is multiple imputation (MI), but Rubin's variance estimator is often biased for the true sampling variability of the point estimator in the control‐based setting. We propose distributional imputation (DI) with corresponding wild bootstrap variance estimation procedure for control‐based sensitivity analyses of recurrent events. We apply control‐based DI to a type I diabetes trial. In the application and simulation studies, DI produced more reasonable standard error estimates than MI with Rubin's combining rules in control‐based sensitivity analyses of recurrent events. 

The surge in advanced manufacturing techniques has led to a paradigm shift in the realm of material design from developing completely new chemistry to tailoring geometry within existing materials. Kirigami, evolved from a traditional cultural and artistic craft of cutting and folding, has emerged as a powerful framework that endows simple 2D sheets with unique mechanical, thermal, optical, and acoustic properties, as well as shape‐shifting capabilities. Given its flexibility, versatility, and ease of fabrication, there are significant efforts in developing kirigami algorithms to create various architectured materials for a wide range of applications. This review summarizes the fundamental mechanisms that govern the transformation of kirigami structures and elucidates how these mechanisms contribute to their distinctive properties, including high stretchability and adaptability, tunable surface topography, programmable shape morphing, and characteristics of bistability and multistability. It then highlights several promising applications enabled by the unique kirigami designs and concludes with an outlook on the future challenges and perspectives of kirigami‐inspired metamaterials toward real‐world applications.