arXiv subjects

Kim May Lee

Publications and source records attributed to Kim May Lee.

4 recordsLinked to original sources

arXiv2025

Comparison of Parametric versus Machine-learning Multiple Imputation in Clinical Trials with Missing Continuous Outcomes

The use of flexible machine-learning (ML) models to generate imputations of missing data within the framework of Multiple Imputation (MI) has recently gained traction, particularly in observational settings. For randomised controlled trials (RCTs), it is unclear whether ML approaches to MI provide valid inference, and whether they outperform parametric MI approaches under complex data generating mechanisms. We conducted two simulations in RCT settings that have incomplete continuous outcomes but fully observed covariates. We compared Complete Cases, standard MI (MI-norm), MI with predictive mean matching (MI-PMM) and ML-based approaches to MI, including classification and regression trees (MI-CART), Random Forests (MI-RF) and SuperLearner when outcomes are missing completely at random or missing at random conditional on treatment/covariate. The first simulation explored non-linear covariate-outcome relationships in the presence/absence of covariate-treatment interactions. The second simulation explored skewed repeated measures, motivated by a trial with digital outcomes. In the absence of interactions, we found that Complete Cases yields reliable inference; MI-norm performs similarly, except when missingness depends on the covariate. ML approaches can lead to smaller mean squared error than Complete Cases and MI-norm in specific non-linear settings, but provide unreliable inference for others. MI-PMM can lead to unreliable inference in several settings. In the presence of complex treatment-covariate interactions, performing MI separately by arm, either with MI-norm, MI-RF or MI-CART, provides inference that has comparable or with better properties compared to Complete Cases when the analysis model omits the interaction. For ML approaches, we observed unreliable inference in terms of bias in the estimated effect and/or its standard error when Rubin's Rules are implemented.

stat.ME↗

arXiv2022

Some performance considerations when using multi-armed bandit algorithms in the presence of missing data

When comparing the performance of multi-armed bandit algorithms, the potential impact of missing data is often overlooked. In practice, it also affects their implementation where the simplest approach to overcome this is to continue to sample according to the original bandit algorithm, ignoring missing outcomes. We investigate the impact on performance of this approach to deal with missing data for several bandit algorithms through an extensive simulation study assuming the rewards are missing at random. We focus on two-armed bandit algorithms with binary outcomes in the context of patient allocation for clinical trials with relatively small sample sizes. However, our results apply to other applications of bandit algorithms where missing data is expected to occur. We assess the resulting operating characteristics, including the expected reward. Different probabilities of missingness in both arms are considered. The key finding of our work is that when using the simplest strategy of ignoring missing data, the impact on the expected performance of multi-armed bandit strategies varies according to the way these strategies balance the exploration-exploitation trade-off. Algorithms that are geared towards exploration continue to assign samples to the arm with more missing responses (which being perceived as the arm with less observed information is deemed more appealing by the algorithm than it would otherwise be). In contrast, algorithms that are geared towards exploitation would rapidly assign a high value to samples from the arms with a current high mean irrespective of the level observations per arm. Furthermore, for algorithms focusing more on exploration, we illustrate that the problem of missing responses can be alleviated using a simple mean imputation approach.

stat.ML↗

arXiv2022

Response-adaptive randomization in clinical trials: from myths to practical considerations

Response-Adaptive Randomization (RAR) is part of a wider class of data-dependent sampling algorithms, for which clinical trials are typically used as a motivating application. In that context, patient allocation to treatments is determined by randomization probabilities that change based on the accrued response data in order to achieve experimental goals. RAR has received abundant theoretical attention from the biostatistical literature since the 1930's and has been the subject of numerous debates. In the last decade, it has received renewed consideration from the applied and methodological communities, driven by well-known practical examples and its widespread use in machine learning. Papers on the subject present different views on its usefulness, and these are not easy to reconcile. This work aims to address this gap by providing a unified, broad and fresh review of methodological and practical issues to consider when debating the use of RAR in clinical trials.

stat.ME↗

arXiv2020

A review of Bayesian perspectives on sample size derivation for confirmatory trials

Sample size derivation is a crucial element of the planning phase of any confirmatory trial. A sample size is typically derived based on constraints on the maximal acceptable type I error rate and a minimal desired power. Here, power depends on the unknown true effect size. In practice, power is typically calculated either for the smallest relevant effect size or a likely point alternative. The former might be problematic if the minimal relevant effect is close to the null, thus requiring an excessively large sample size. The latter is dubious since it does not account for the a priori uncertainty about the likely alternative effect size. A Bayesian perspective on the sample size derivation for a frequentist trial naturally emerges as a way of reconciling arguments about the relative a priori plausibility of alternative effect sizes with ideas based on the relevance of effect sizes. Many suggestions as to how such `hybrid' approaches could be implemented in practice have been put forward in the literature. However, key quantities such as assurance, probability of success, or expected power are often defined in subtly different ways in the literature. Starting from the traditional and entirely frequentist approach to sample size derivation, we derive consistent definitions for the most commonly used `hybrid' quantities and highlight connections, before discussing and demonstrating their use in the context of sample size derivation for clinical trials.

stat.AP↗