arXiv subjects

Yongdong Ouyang

Publications and source records attributed to Yongdong Ouyang.

5 recordsLinked to original sources

arXiv2026

Which Small-Sample Correction Should Be Used When Analyzing Stepped-Wedge Designs with Time-Varying Treatment Effects?

Stepped-wedge cluster randomized trials (SW-CRTs) evaluate interventions rolled out across clusters over time. Standard analyses typically use immediate-treatment (IT) models, which assume effects begin at crossover and remain constant thereafter. When effects vary with exposure duration, IT models may misrepresent target effects. Exposure-time indicator (ETI) models address this by allowing treatment effects to differ by time since exposure and by targeting the time-averaged treatment effect (TATE) and long-term effect (LTE). Like IT models, ETI models require specification of a random-effects structure, which is often misspecified, and the performance of robust variance estimators (RVEs) in this setting is not well understood. We review RVEs for ETI models and evaluate them in simulation studies with continuous and binary outcomes under correctly specified (binary only) and misspecified random-effects structures. We compare the classic sandwich, Kauermann-Carroll (KC), Mancl-DeRouen (MD), and Morel-Bokossa-Neerchal (MBN) estimators for inference on the TATE and LTE. Our simulations show that under misspecified random-effects structures, model-based standard errors (SE) produced undercoverage, whereas RVEs improved performance. For continuous outcomes, MD with a t-distribution and degrees of freedom equal to the number of clusters minus two gave the most consistent coverage probabilities. For binary outcomes, MBN was the only consistently reliable option. MD, however, could be unstable in one-cluster-per-sequence designs because of data sparsity. Across scenarios, both model-based SE and RVE for LTE were unstable, indicating that greater caution is needed when targeting LTE under ETI models.

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arXiv2026

Remote, bivariate expert elicitation to determine the prior probability distribution for sample size calculation in a Bayesian non-inferiority multicenter randomized controlled trial (Croup Dosing Trial)

Prior distributions must be specified for the parameters of interest in a Bayesian clinical trial. When existing evidence on the effects of the trial interventions is limited, prior distributions can be constructed with expert elicitation. However, conventional elicitation requires face-to-face interactions and intensive pre-elicitation training, which can be infeasible. Our remote elicitation was based on established expert elicitation methods. We used bivariate prior distributions for dependencies between elicited quantities. We elicited a prior distribution for the Croup Dosing Trial, which will assess the number of return visits to the emergency department within 7 days in children with croup. This trial evaluates the non-inferiority of 0.15 mg/kg of dexamethasone, compared to the standard dose of 0.60 mg/kg to treat croup. We conducted three remote workshops to elicit expert beliefs on the efficacy of the two doses of dexamethasone. Each workshop consisted of two survey rounds, separated by a group discussion. Prior to the workshop, experts reviewed provided literature on the effects of the two doses of dexamethasone. Beliefs were aggregated with expert-specific bivariate distributions. The aggregated distribution and surveyed non-inferiority margin determined the sample size. Twelve emergency medicine physicians participated in our remote elicitation exercise. The elicitation generated a prior distribution centered at 6% for the 0.60 mg/kg dose and 8% for the 0.15 mg/kg dose. The aggregated prior distribution produced a sample size of 1850, based on a non-inferiority margin of 4%. We elicited a prior distribution that incorporated past evidence and expert opinion. The elicited prior is consistent with literature on the efficacy of the dexamethasone doses in treating croup. Our approach demonstrates the feasibility of remotely eliciting bivariate distributions for clinical trials.

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arXiv2025

A systematic review of sample size determination in Bayesian randomized clinical trials: full Bayesian methods are rarely used

Utilizing Bayesian methods in clinical trials has become increasingly popular, as they can incorporate historical data and expert opinions into the design and allow for smaller sample sizes to reduce costs while providing reliable and robust statistical results. Sample size determination (SSD) is a key aspect of clinical trial design and various methods for Bayesian sample size determination are available. However, it is unclear how these methods are being used in practice. A systematic literature review was conducted to understand how sample sizes for Bayesian randomized clinical trials (RCTs) are determined and inform the design of future Bayesian trials. We searched five databases in May 2023, and updated in January 2025, including efficacy RCTs in humans which utilized a Bayesian framework for the primary data analysis, published in English, and enrolled participants between 2009 and 2024. The literature search produced 19,182 records, of which 105 studies were selected for data extraction. Results show that the most common method for SSD in Bayesian RCTs was a hybrid approach in which elements of Bayesian and frequentist theory are combined. Many RCTs did not provide a justification for SSD, while fully Bayesian methods were rarely used in practice, despite significant theoretical development. Our review also revealed a lack of standardized reporting, making it challenging to review the SSD. The CONSORT statement for reporting RCTs states that sample size calculations must be reported, which was poorly adhered to. Among RCTs that reported SSD, relevant information was frequently omitted from the reports and discussed in poorly structured supplementary materials. Thus, there is a critical need for greater transparency, standardization and translation of relevant methodology in Bayesian RCTs.

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arXiv2025

Priors from Envisioned Posterior Judgments: A Novel Elicitation Approach With Application to Bayesian Clinical Trials

Background: The uptake of formalized prior elicitation from experts in Bayesian clinical trials has been limited due to challenges such as complex statistical modeling, lack of practical tools, and the cognitive burden placed on experts arising from needing to quantify their uncertainty probabilistically. Existing methods also fail to address prior-posterior coherence, i.e., how do we ensure that the posterior distribution, obtained mathematically from combining the estimated prior with the trial data, reflects the expert's actual posterior beliefs? Method: In this study, we propose a new elicitation approach that effectuates prior-posterior coherence and reduces cognitive burden. This is achieved by eliciting expert responses, comprising point estimates only, about envisioned posterior judgments under various data outcomes and inferring the prior distribution by minimizing discrepancies between these responses and expected responses derived from the posterior distribution. Via an iterative process, experts receive feedback on the degree of coherency of their responses, and are invited to revise their responses to achieve greater coherency. The feasibility and potential value of this new approach are illustrated through an application to an ongoing trial. Results: We involved 10 experts from Walk 'n watch trial research team. Experts were presented with 16 hypothetical outcome scenarios to experts and elicit the priors followed by the developed elicitation framework. Following two rounds of elicitation, experts' judgments showed substantial improvement in coherency, demonstrating the practical applicability of the proposed elicitation approach. Conclusion: The proposed method provides a practical solution to the challenges of formalized prior elicitation in Bayesian clinical trials by addressing prior-posterior coherence and reducing cognitive demands on experts.

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arXiv2024

Maintaining the validity of inference from linear mixed models in stepped-wedge cluster randomized trials under misspecified random-effects structures

Linear mixed models are commonly used in analyzing stepped-wedge cluster randomized trials (SW-CRTs). A key consideration for analyzing a SW-CRT is accounting for the potentially complex correlation structure, which can be achieved by specifying a random effects structure. Common random effects structures for a SW-CRT include random intercept, random cluster-by-period, and discrete-time decay. Recently, more complex structures, such as the random intervention structure, have been proposed. In practice, specifying appropriate random effects can be challenging. Robust variance estimators (RVE) may be applied to linear mixed models to provide consistent estimators of standard errors of fixed effect parameters in the presence of random-effects misspecification. However, there has been no empirical investigation of RVE for SW-CRT. In this paper, we first review five RVEs (both standard and small-sample bias-corrected RVEs) that are available for linear mixed models. We then describe a comprehensive simulation study to examine the performance of these RVEs for SW-CRTs with a continuous outcome under different data generators. For each data generator, we investigate whether the use of a RVE with either the random intercept model or the random cluster-by-period model is sufficient to provide valid statistical inference for fixed effect parameters, when these working models are subject to misspecification. Our results indicate that the random intercept and random cluster-by-period models with RVEs performed similarly. The CR3 RVE estimator, coupled with the number of clusters minus two degrees of freedom correction, consistently gave the best coverage results, but could be slightly conservative when the number of clusters was below 16. We summarize the implications of our results for linear mixed model analysis of SW-CRTs in practice.

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