arXiv subjects

Marius Thomas

Publications and source records attributed to Marius Thomas.

5 recordsLinked to original sources

arXiv2026

An ionic clock qubit inside a circular Rydberg atom

Neutral atoms trapped in optical tweezers and excited to Rydberg states, together with trapped ions, are among the most advanced platforms for quantum simulation and quantum computing. Current experiments often rely on additional atoms in neighboring traps to encode ancilla qubits for local manipulation and readout. Here, we demonstrate a dual ion-Rydberg system comprising two qubits encoded in two individually controlled electrons of the same alkaline-earth atom. The first, a microwave qubit, is encoded in a pair of circular Rydberg states, while the second, an optical qubit, is encoded on a narrow quadrupole transition of the Rydberg atom's ionic core. We demonstrate coherent control of the optical qubit and achieve coherence times of several hundred microseconds under dynamical decoupling. Furthermore, we realize coherent coupling between the two electrons via electrostatic quadrupole interactions over the large separation between the Rydberg electron and the ionic core, and map out its angular tunability. Finally, we demonstrate a two-qubit operation, reminiscent of a M{\o}lmer-S{\o}rensen gate, that evolves through an entangled state of the two qubits driven by the quadrupole coupling. Our work opens a pathway to exploit a pair of individually controlled electronic qubits with tunable coupling for quantum simulation and quantum metrology.

physics.atom-ph↗

arXiv2018

Identifying treatment effect heterogeneity in dose-finding trials using Bayesian hierarchical models

An important task in drug development is to identify patients, which respond better or worse to an experimental treatment. Identifying predictive covariates, which influence the treatment effect and can be used to define subgroups of patients, is a key aspect of this task. Analyses of treatment effect heterogeneity are however known to be challenging, since the number of possible covariates or subgroups is often large, while samples sizes in earlier phases of drug development are often small. In addition, distinguishing predictive covariates from prognostic covariates, which influence the response independent of the given treatment, can often be difficult. While many approaches for these types of problems have been proposed, most of them focus on the two-arm clinical trial setting, where patients are given either the treatment or a control. In this paper we consider parallel groups dose-finding trials, in which patients are administered different doses of the same treatment. To investigate treatment effect heterogeneity in this setting we propose a Bayesian hierarchical dose-response model with covariate effects on dose-response parameters. We make use of shrinkage priors to prevent overfitting, which can easily occur, when the number of considered covariates is large and sample sizes are small. We compare several such priors in simulations and also investigate dependent modeling of prognostic and predictive effects to better distinguish these two types of effects. We illustrate the use of our proposed approach using a Phase II dose-finding trial and show how it can be used to identify predictive covariates and subgroups of patients with increased treatment effects.

stat.ME↗

arXiv2018

A multiple comparison procedure for dose-finding trials with subpopulations

Identifying subgroups of patients with an enhanced response to a new treatment has become an area of increased interest in the last few years. When there is knowledge about possible subpopulations with an enhanced treatment effect before the start of a trial it might be beneficial to set up a testing strategy, which tests for a significant treatment effect not only in the full population, but also in these prespecified subpopulations. In this paper we present a parametric multiple testing approach for tests in multiple populations for dose-finding trials. Our approach is based on the MCP-Mod methodology, which uses multiple comparison procedures to test for a dose-response signal, while considering multiple possible candidate dose-response shapes. Our proposed methods allow for heteroscedasticity between populations and control the FWER over tests in multiple populations and for multiple candidate models. We show in simulations, that the proposed multi-population testing approaches can increase the power to detect a significant dose-response signal over the standard single-population MCP-Mod, when the considered subpopulation has an enhanced treatment effect.

stat.ME↗

arXiv2018

Subgroup identification in dose-finding trials via model-based recursive partitioning

An important task in early phase drug development is to identify patients, which respond better or worse to an experimental treatment. While a variety of different subgroup identification methods have been developed for the situation of trials that study an experimental treatment and control, much less work has been done in the situation when patients are randomized to different dose groups. In this article we propose new strategies to perform subgroup analyses in dose-finding trials and discuss the challenges, which arise in this new setting. We consider model-based recursive partitioning, which has recently been applied to subgroup identification in two arm trials, as a promising method to tackle these challenges and assess its viability using a real trial example and simulations. Our results show that model-based recursive partitioning can be used to identify subgroups of patients with different dose-response curves and improves estimation of treatment effects and minimum effective doses, when heterogeneity among patients is present.

stat.ME↗

arXiv2016

Comparing Approaches to Treatment Effect Estimation for Subgroups in Clinical Trials

Identifying subgroups, which respond differently to a treatment, both in terms of efficacy and safety, is an important part of drug development. A well-known challenge in exploratory subgroup analyses is the small sample size in the considered subgroups, which is usually too low to allow for definite comparisons. In early phase trials this problem is further exaggerated, because limited or no clinical prior information on the drug and plausible subgroups is available. We evaluate novel strategies for treatment effect estimation in these settings in a simulation study motivated by real clinical trial situations. We compare several approaches to estimate treatment effects for selected subgroups, employing model averaging, resampling and Lasso regression methods. Two subgroup identification approaches are employed, one based on categorization of covariates and the other based on splines. Our results show that naive estimation of the treatment effect, which ignores that a selection has taken place, leads to bias and overoptimistic conclusions. For the considered simulation scenarios virtually all evaluated novel methods provide more adequate estimates of the treatment effect for selected subgroups, in terms of bias, MSE and confidence interval coverage.

stat.CO↗