Clinical Trial and Observational Studies: New Design and Estimation Techniques

Yanran Li Chair
 
Sunday, Aug 3: 2:00 PM - 3:50 PM
4005 
Contributed Papers 
Music City Center 
Room: CC-205C 

Main Sponsor

International Chinese Statistical Association

Presentations

A Minimax Approach for Optimal Incentive Policy Learning

While strategic incentive policies are essential in personalized services, variations in user responses and revenue potentials create significant challenges in identifying optimal incentive policies. Existing literature typically falls short in fully identification of all user types and often assumes a uniform conversion revenue, leading to inefficient incentive allocations. In this study, we propose a minimax policy learning approach within a counterfactual principal strata framework. A value function, accommodating varying rewards across six potentially non-identifiable principal strata, is designed to minimize the worst-case value loss relative to three alternative policies: never-treat, always-treat, and oracle. To learn an optimal policy, we introduce three estimators: Principal Outcome Regression (P-OR), Principal Inverse Propensity Scoring (P-IPS), and Principal Doubly Robust (P-DR), providing theoretical guarantees for their unbiasedness, robustness, and regret upper bound. Extensive numerical experiments validate the effectiveness and superiority of our proposed approach. 

Keywords

Policy learning

Minimax

Counterfactual principal strata

Partial identification

Causal inference 

Co-Author(s)

Yue Liu, School of Statistics, Renmin University of China
Hao Mei, School of Statistics, Renmin University of China

First Author

Chenyang Li, School of Statistics, Renmin University of China

Presenting Author

Hao Mei, School of Statistics, Renmin University of China

Bayesian Functional Factor Analysis and Bayesian Functional Principal Component Analysis

This research explores the application of Functional Data Analysis (FDA) to uncover time-varying patterns in complex dynamic systems. FDA treats data as smooth, continuous functions rather than discrete observations, enabling the analysis of temporal dependencies and underlying dynamic structures. Building on this framework, we apply Bayesian Principal Component Analysis (BPCA) and Bayesian Factor Analysis (BFA) to enhance the study of time-dependent data. BPCA is extended to functional data to address challenges in dimensionality reduction for high-dimensional and noisy datasets, providing robust uncertainty quantification and improved interpretability of temporal principal components. Complementing this, BFA is applied at ten distinct time points, using smoothing splines to visualize dynamic factor loadings and scores, capturing the evolution of latent structures over time. Together, these Bayesian approaches advance our understanding of temporal correlations in dynamic systems, offering a flexible and detailed methodology for applications such as gene regulatory networks and other evolving processes. 

Keywords

Functional Data Analysis (FDA)

Bayesian Principal Component Analysis (BPCA)

Bayesian Factor Analysis (BFA)

Temporal Dependencies

Dynamic Systems


Smoothing Splines 

First Author

Boshi Zhao, Northern Illinois University

Presenting Author

Boshi Zhao, Northern Illinois University

Gaussianized Design Optimization for Covariate Balance in Randomized Experiments

Achieving covariate balance in randomized experiments enhances the precision of treatment effect estimation. However, existing methods often require heuristic adjustments based on domain knowledge and are primarily developed for binary treatments. This paper presents Gaussianized Design Optimization, a novel framework for optimally balancing covariates in experimental design. The core idea is to Gaussianize the treatment assignments: we model treatments as transformations of random variables drawn from a multivariate Gaussian distribution, converting the design problem into a nonlinear continuous optimization over Gaussian covariance matrices. Compared to existing methods, our approach offers significant flexibility in optimizing covariate balance across a diverse range of designs and covariate types. Adapting the Burer-Monteiro approach for solving semidefinite programs, we introduce first-order local algorithms for optimizing covariate balance, improving upon several widely used designs. Furthermore, we develop inferential procedures for constructing design-based confidence intervals under Gaussianization and extend the framework to accommodate continuous treatments. Simulations demonstrate the effectiveness of Gaussianization in multiple practical scenarios. 

Keywords

Optimal Experimental Design

Covariate Balance

Continuous Treatments

Mehler's Formula 

Co-Author(s)

Tengyuan Liang, The University of Chicago
Panagiotis Toulis, The University of Chicago, Booth School of Business

First Author

Wenxuan Guo, University of Chicago

Presenting Author

Wenxuan Guo, University of Chicago

Multi-arm multi-stage survival trial design with arm-specific stopping rule

Traditional two-arm randomized trial designs have played a pivotal role in
establishing the efficacy of medical interventions. However, their efficiency is
often compromised when confronted with multiple experimental treatments
or limited resources. In response to these challenges, the multi-arm multi-stage
designs have emerged, enabling the simultaneous evaluation of multiple
treatments within a single trial. In such an approach, if an arm meets
efficacy success criteria at an interim stage, the whole trial stops and the arm
is selected for further study. However when multiple treatment arms are
active, stopping the trial at the moment one arm achieves success diminishes
the probability of selecting the best arm. To address this issue, we have
developed a group sequential multi-arm multi-stage survival trial design
with an arm-specific stopping rule. The proposed method controls the
familywise type I error in a strong sense and selects the best promising
treatment arm with a high probability. 

Keywords

Multi-arm multi-stage

group sequential design

log-rank test

sequential conditional probability ratio test

time-to-event 

Co-Author(s)

Yimei Li
Liang Zhu, St. Jude Children's Research Hospital
Tushar Patni, St Jude

First Author

Jianrong Wu, University of New Mexico, Dept. of Internal Medicine

Presenting Author

Jianrong Wu, University of New Mexico, Dept. of Internal Medicine

Optimal concordant tests

In meta-analysis, unlike model-based methods, such as fixed- or random-effect models, the p-value combining methods are distribution-free and robust. How to appropriately and powerfully combine p-values obtained from various sources remains an important but challenging topic in statistical inference. For cases where all or the majority of the individual alternative hypotheses have the same but unknown direction, concordant tests based on one-sided p-values can substantially improve the detecting power. However, there exist no uniformly most powerful tests; therefore, how to choose a robust and powerful test to combine one-sided p-values for a given data set is desirable. In this paper, we propose and study a class of gamma distribution-based concordant tests. Those concordant tests are optimal under specific conditions. An asymptotically optimal concordant test is also studied. The excellent performances of the proposed tests were demonstrated through numeric simulation study and real data example. 

Keywords

chi-square test

constrained likelihood ratio test

gamma distribution

meta-analysis

uniformly most powerful test 

First Author

Zhongxue Chen

Presenting Author

Zhongxue Chen

Robust Sensitivity Analysis for Inverse Probability Weighting Estimation under Non-Overlap

Sensitivity analysis is essential for evaluating the robustness of causal conclusions in observational studies, particularly when key assumptions such as no unmeasured confounding and overlap may be violated. In this paper, we propose a robust marginal sensitivity model that accounts for the potential heterogeneity in unmeasured confounding strength and allows for non-overlap between treated and control units. We focus particularly on overlap-weighted average treatment effect that can better accommodate extreme treatment probabilities, and construct confidence intervals for the average treatment effect under given constraints on the violation of unconfoundedness and overlap. Our analysis utilizes constraints from the covariate balancing property of the true propensity score, and the proposed inference is applicable to general Z-estimation with overidentified equations and unmeasured variables. 

Keywords

Causal inference

Sensitivity analysis

Unmeasured confounding

Non-Overlap

Overlap-weighted average treatment effect 

Co-Author

Xinran Li

First Author

Han Cui, University of Illinois Urbana-Champaign

Presenting Author

Han Cui, University of Illinois Urbana-Champaign

Sensitivity Analysis of Lost to Follow-up in Life History Data with Multiple Imputation

Life history data describes a process that progresses through various stages before reaching a terminal event, providing detailed insights into the entire disease trajectory. It is increasingly used in health research to evaluate treatment effects, risk factors, and policy implementations. However, handling loss to follow-up (LTF) remains a major challenge since conventional multistate models often assume that LTF-induced censoring is independent of the life history process, an assumption that may not hold in practice. This paper addresses this issue through sensitivity analysis, which characterizes deviations from independent censoring and evaluates the impact on treatment effect estimation. We extend the classical multistate model to include separate pre- and post-LTF transition intensities. Using trace data informed sensitivity assumption, we apply a model-based multiple imputation (MI) to generate the entire latent transitions before and after LTF. We assess the performance of our method through simulation and apply the method using real-world data to assess the impact of the World Health Organization's Treat All policy on HIV disease progression. 

Keywords

life history data

multistate model

lost to follow-up

multiple imputation.

sensitivity analysis 

First Author

Hongbing Zhang, University of Kentucky

Presenting Author

Hongbing Zhang, University of Kentucky