arXiv subjects

Fabio Rigat

Publications and source records attributed to Fabio Rigat.

6 recordsLinked to original sources

arXiv2026

Calibration of clinical trial sample size based on design utility

Clinical trial design relies on both statistical and clinical considerations for pre-specification of potentially practice-changing target treatment effects. As larger trials tend to be associated with high power and modest minimal detectable benefit, trial sample size is typically calibrated with reference to relevant precedents to prevent overpowering. Albeit trial sponsors and regulators are accustomed to this practice, there is scope for simplification to enhance the robustness, transparency and cross-trial consistency of this aspect of the design process. To this end, a design utility index is proposed here as a formal basis for sample size calibration, balancing the increase in power at higher sample sizes against the corresponding reduction in the magnitude of minimum detectable treatment effects, without requiring additional statistical assumptions or bespoke software. Application of utility calibration to a broad range of designs demonstrates consistency with regulatory expectations for minimum power, particularly in confirmatory settings, and effective protection against overpowering and against overly aggressive interim analyses.

stat.AP↗

arXiv2025

Equipoise calibration of clinical trial design

Clinical trial design ensures that primary analysis outcomes have strong statistical properties. However, mainstream methodology for randomised study design does not establish a formal link between statistical and clinical significance. This paper contributes to bridging this gap by calibrating the operational characteristics of primary trial outcomes to establishing clinical equipoise imbalance. Common late phase designs are shown to provide at least 90% evidence of equipoise imbalance. Designs carrying 95% power at 5% false positive rate are shown to demonstrate 95% evidence of equipoise imbalance, providing an operational definition of a robustly powered study. Equipoise calibration is applied to design of clinical development plans comprising phase 2 and phase 3 studies using standard oncology endpoints. Commonly used power and false positive error rates are shown to provide strong equipoise imbalance when positive outcomes are observed in both phase 2 and phase 3. Establishing strong equipoise imbalance based on inconsistent outcomes of phase 2 and phase 3 studies is shown to require large sample sizes unlikely to be associated with clinically meaningful effect sizes.

stat.AP↗

arXiv2023

A Conservative Approach to Leveraging External Evidence for Effective Clinical Trial Design

Prior probabilities of clinical hypotheses are not systematically used for clinical trial design yet, due to a concern that poor priors may lead to poor decisions. To address this concern, a conservative approach to Bayesian trial design is illustrated here, requiring that the operational characteristics of the primary trial outcome are stronger than the prior. This approach is complementary to current Bayesian design methods, in that it insures against prior-data conflict by defining a sample size commensurate to a discrete design prior. This approach is ethical, in that it requires designs appropriate to achieving pre-specified levels of clinical equipoise imbalance. Practical examples are discussed, illustrating design of trials with binary or time to event endpoints. Moderate increases in phase II study sample size are shown to deliver strong levels of overall evidence for go/no-go clinical development decisions. Levels of negative evidence provided by group sequential confirmatory designs are found negligible, highlighting the importance of complementing efficacy boundaries with non-binding futility criteria.

stat.ME↗

arXiv2014

Bayesian Density Estimation via Multiple Sequential Inversions of 2-D Images with Application in Electron Microscopy

We present a new Bayesian methodology to learn the unknown material density of a given sample by inverting its two-dimensional images that are taken with a Scanning Electron Microscope. An image results from a sequence of projections of the convolution of the density function with the unknown microscopy correction function that we also learn from the data. We invoke a novel design of experiment, involving imaging at multiple values of the parameter that controls the sub-surface depth from which information about the density structure is carried, to result in the image. Real-life material density functions are characterised by high density contrasts and typically are highly discontinuous, implying that they exhibit correlation structures that do not vary smoothly. In the absence of training data, modelling such correlation structures of real material density functions is not possible. So we discretise the material sample and treat values of the density function at chosen locations inside it as independent and distribution-free parameters. Resolution of the available image dictates the discretisation length of the model; three models pertaining to distinct resolution classes are developed. We develop priors on the material density, such that these priors adapt to the sparsity inherent in the density function. The likelihood is defined in terms of the distance between the convolution of the unknown functions and the image data. The posterior probability density of the unknowns given the data is expressed using the developed priors on the density and priors on the microscopy correction function as elicitated from the Microscopy literature. We achieve posterior samples using an adaptive Metropolis-within-Gibbs inference scheme. The method is applied to learn the material density of a 3-D sample of a real nano-structure and of simulated alloy samples.

stat.AP↗

arXiv2010

Semi-parametric dynamic time series modelling with applications to detecting neural dynamics

This paper illustrates novel methods for nonstationary time series modeling along with their applications to selected problems in neuroscience. These methods are semi-parametric in that inferences are derived by combining sequential Bayesian updating with a non-parametric change-point test. As a test statistic, we propose a Kullback--Leibler (KL) divergence between posterior distributions arising from different sets of data. A closed form expression of this statistic is derived for exponential family models, whereas standard Markov chain Monte Carlo output is used to approximate its value and its critical region for more general models. The behavior of one-step ahead predictive distributions under our semi-parametric framework is described analytically for a dynamic linear time series model. Conditions under which our approach reduces to fully parametric state-space modeling are also illustrated. We apply our methods to estimating the functional dynamics of a wide range of neural data, including multi-channel electroencephalogram recordings, longitudinal behavioral experiments and in-vivo multiple spike trains recordings. The estimated dynamics are related to the presentation of visual stimuli, to the evaluation of a learning performance and to changes in the functional connections between neurons over a sequence of experiments.

stat.AP↗

arXiv2008

Parallel hierarchical sampling: a practical multiple-chains sampler for Bayesian model selection

This paper introduces the parallel hierarchical sampler (PHS), a Markov chain Monte Carlo algorithm using several chains simultaneously. The connections between PHS and the parallel tempering (PT) algorithm are illustrated, convergence of PHS joint transition kernel is proved and and its practical advantages are emphasized. We illustrate the inferences obtained using PHS, parallel tempering and the Metropolis-Hastings algorithm for three Bayesian model selection problems, namely Gaussian clustering, the selection of covariates for a linear regression model and the selection of the structure of a treed survival model.

stat.CO↗