arXiv subjects

Scott Hummel

Publications and source records attributed to Scott Hummel.

3 recordsLinked to original sources

arXiv2025

Integrating Prioritized and Non-Prioritized Structures in Win Statistics

Composite endpoints are frequently used as primary or secondary analyses in cardiovascular clinical trials to increase clinical relevance and statistical efficiency. Alternatively, the Win Ratio (WR) and other Win Statistics (WS) analyses rely on a strict hierarchical ordering of endpoints, assigning higher priority to clinically important endpoints. However, determining a definitive endpoint hierarchy can be challenging and may not adequately reflect situations where endpoints have comparable importance. In this study, we discuss the challenges of endpoint prioritization, underscore its critical role in WS analyses, and propose Rotation WR (RWR), a hybrid prioritization framework that integrates both prioritized and non-prioritized structures. By permitting blocks of equally-prioritized endpoints, RWR accommodates endpoints of equal or near equal clinical importance, recurrent events, and contexts requiring individualized shared decision making. Statistical inference for RWR is developed using U-statistics theory, including the hypothesis testing procedure and confidence interval construction. Extensions to two additional WS measures, Rotation Net Benefit and Rotation Win Odds, are also provided. Through extensive simulation studies involving multiple time-to-event endpoints, including recurrent events, we demonstrate that RWR achieves valid type I error control, desirable statistical power, and accurate confidence interval coverage. We illustrate both the methodological and practical insights of our work in a case study on endpoint prioritization with the SPRINT clinical trial, highlighting its implications for real-world clinical trial studies.

stat.ME↗

arXiv2025

Practical considerations when designing an online learning algorithm for an app-based mHealth intervention

The ubiquitous nature of mobile health (mHealth) technology has expanded opportunities for the integration of reinforcement learning into traditional clinical trial designs, allowing researchers to learn individualized treatment policies during the study. LowSalt4Life 2 (LS4L2) is a recent trial aimed at reducing sodium intake among hypertensive individuals through an app-based intervention. A reinforcement learning algorithm, which was deployed in one of the trial arms, was designed to send reminder notifications to promote app engagement in contexts where the notification would be effective, i.e., when a participant is likely to open the app in the next 30-minute and not when prior data suggested reduced effectiveness. Such an algorithm can improve app-based mHealth interventions by reducing participant burden and more effectively promoting behavior change. We encountered various challenges during the implementation of the learning algorithm, which we present as a template to solving challenges in future trials that deploy reinforcement learning algorithms. We provide template solutions based on LS4L2 for solving the key challenges of (i) defining a relevant reward, (ii) determining a meaningful timescale for optimization, (iii) specifying a robust statistical model that allows for automation, (iv) balancing model flexibility with computational cost, and (v) addressing missing values in gradually collected data.

stat.ME↗

arXiv2024

Generalizing the Finkelstein-Schoenfeld Test to Incorporate Multiple Alternating Thresholds

Composite endpoints consisting of both terminal and non-terminal events, such as death and hospitalization, are frequently used in cardiovascular clinical trials. The Finkelstein-Schoenfeld (FS) test provides a way to employ a hierarchical structure to combine fatal and non-fatal events by giving death information an absolute priority, which may limit the contribution of clinically meaningful non-fatal events. To provide a more flexible alternative, we propose the Finkelstein-Schoenfeld with Multiple Thresholds (FS-MT) test, which extends the standard FS test by incorporating multiple thresholds applied sequentially and alternating across endpoints. A weighted adaptive approach is also developed to help determine the thresholds in FS-MT. The proposed approach retains the statistical properties of the FS test while allowing more flexible use of information from lower-priority events. We evaluate the operating characteristics of the proposed test through simulations that vary the follow-up time, the correlation between events, and the treatment effect sizes. A case study based on the Digitalis Investigation Group clinical trial data is presented to further illustrate our proposed method. An R package ``FSMT'' that implements the proposed methodology has been developed.

stat.ME↗