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Ying Yuan

Publications and source records attributed to Ying Yuan.

At least 73 records · Page 4Linked to original sources

SAM: Self-adapting Mixture Prior to Dynamically Borrow Information from Historical Data in Clinical Trials

Mixture priors provide an intuitive way to incorporate historical data while accounting for potential prior-data conflict by combining an informative prior with a non-informative prior. However, pre-specifying the mixing weight for each component remains a crucial challenge. Ideally, the mixing weight should reflect the degree of prior-data conflict, which is often unknown beforehand, posing a significant obstacle to the application and acceptance of mixture priors. To address this challenge, we introduce self-adapting mixture (SAM) priors that determine the mixing weight using likelihood ratio test statistics or Bayes factor. SAM priors are data-driven and self-adapting, favoring the informative (non-informative) prior component when there is little (substantial) evidence of prior-data conflict. Consequently, SAM priors achieve dynamic information borrowing. We demonstrate that SAM priors exhibit desirable properties in both finite and large samples and achieve information-borrowing consistency. Moreover, SAM priors are easy to compute, data-driven, and calibration-free, mitigating the risk of data dredging. Numerical studies show that SAM priors outperform existing methods in adopting prior-data conflicts effectively. We developed an R package and web application that are freely available to facilitate the use of SAM priors.

stat.ME↗

Design and Sample Size Determination for Multiple-dose Randomized Phase II Trials for Dose Optimization

The conventional more-is-better dose selection paradigm, which targets the maximum tolerated dose (MTD), is not suitable for the development of targeted therapies and immunotherapies as the efficacy of these novel therapies may not increase with the dose. The U.S. Food and Drug Administration (FDA) has launched Project Optimus "to reform the dose optimization and dose selection paradigm in oncology drug development", and recently published a draft guidance on dose optimization, which outlines various approaches to achieve this goal. One highlighted approach involves conducting a randomized phase II trial following the completion of a phase I trial, where multiple doses (typically including the MTD and one or two doses lower than the MTD) are compared to identify the optimal dose that maximizes the benefit-risk tradeoff. This paper focuses on the design of such a multiple-dose randomized trial, specifically the determination of the sample size. We propose a MERIT (Multiple-dosE RandomIzed Trial design for dose optimization based on toxicity and efficacy) design that can be easily implemented with pre-calculated decision boundaries included in the protocol. We generalized the standard definitions of type I error and power to accommodate the unique characteristics of dose optimization and derived a decision rule along with an algorithm to determine the optimal sample size. Simulation studies demonstrate that the resulting MERIT design has desirable operating characteristics. To facilitate the implementation of the MERIT design, we provide software, available at www.trialdesign.org.

stat.ME↗

Search for light dark matter from atmosphere in PandaX-4T

We report a search for light dark matter produced through the cascading decay of $η$ mesons, which are created as a result of inelastic collisions between cosmic rays and Earth's atmosphere. We introduce a new and general framework, publicly accessible, designed to address boosted dark matter specifically, with which a full and dedicated simulation including both elastic and quasi-elastic processes of Earth attenuation effect on the dark matter particles arriving at the detector is performed. In the PandaX-4T commissioning data of 0.63 tonne$\cdot$year exposure, no significant excess over background is observed. The first constraints on the interaction between light dark matter generated in the atmosphere and nucleus through a light scalar mediator are obtained. The lowest excluded cross-section is set at $5.9 \times 10^{-37}{\rm cm^2}$ for dark matter mass of $0.1$ MeV$/c^2$ and mediator mass of 300 MeV$/c^2$. The lowest upper limit of $η$ to dark matter decay branching ratio is $1.6 \times 10^{-7}$.

hep-ex↗

A Search for Light Fermionic Dark Matter Absorption on Electrons in PandaX-4T

We report a search on a sub-MeV fermionic dark matter absorbed by electrons with an outgoing active neutrino using the 0.63 tonne-year exposure collected by PandaX-4T liquid xenon experiment. No significant signals are observed over the expected background. The data are interpreted into limits to the effective couplings between such dark matter and electrons. For axial-vector or vector interactions, our sensitivity is competitive in comparison to existing astrophysical bounds on the decay of such dark matter into photon final states. In particular, we present the first direct detection limits for an axial-vector (vector) interaction which are the strongest in the mass range from 25 to 45 (35 to 50) keV/c$^2$.

hep-ex↗

Bayesian Nonparametric Common Atoms Regression for Generating Synthetic Controls in Clinical Trials

The availability of electronic health records (EHR) has opened opportunities to supplement increasingly expensive and difficult to carry out randomized controlled trials (RCT) with evidence from readily available real world data. In this paper, we use EHR data to construct synthetic control arms for treatment-only single arm trials. We propose a novel nonparametric Bayesian common atoms mixture model that allows us to find equivalent population strata in the EHR and the treatment arm and then resample the EHR data to create equivalent patient populations under both the single arm trial and the resampled EHR. Resampling is implemented via a density-free importance sampling scheme. Using the synthetic control arm, inference for the treatment effect can then be carried out using any method available for RCTs. Alternatively the proposed nonparametric Bayesian model allows straightforward model-based inference. In simulation experiments, the proposed method exhibits higher power than alternative methods in detecting treatment effects, specifically for non-linear response functions. We apply the method to supplement single arm treatment-only glioblastoma studies with a synthetic control arm based on historical trials.

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A First Search for Solar $^8$B Neutrino in the PandaX-4T Experiment using Neutrino-Nucleus Coherent Scattering

A search for interactions from solar $^8$B neutrinos elastically scattering off xenon nuclei using PandaX-4T commissioning data is reported. The energy threshold of this search is further lowered compared with the previous search for dark matter, with various techniques utilized to suppress the background that emerges from data with the lowered threshold. A blind analysis is performed on the data with an effective exposure of 0.48 tonne$\cdot$year, and no significant excess of events is observed. Among results obtained using the neutrino-nucleus coherent scattering, our results give the best constraint on the solar $^8$B neutrino flux. We further provide a more stringent limit on the cross section between dark matter and nucleon in the mass range from 3 to 9 GeV/c$^2$.

hep-ex↗

Measurement of Double Beta Decay Half-life of $^{136}$Xe with the PandaX-4T Detector

Precise measurement of two-neutrino double beta decay (DBD) half-life is an important step for the searches of Majorana neutrinos with neutrinoless double beta decay. We report the measurement of DBD half-life of $^{136}$Xe using the PandaX-4T dual-phase Time Projection Chamber (TPC) with 3.7-tonne natural xenon and the first 94.9-day physics data release. The background model in the fiducial volume is well constrained in situ by events in the outer active region. With a $^{136}$Xe exposure of 15.5 kg-year, we establish the half-life as $2.27 \pm 0.03 (stat.)\pm 0.10 (syst.)\times 10^{21}$ years. This is the first DBD half-life measurement with natural xenon and demonstrates the physics capability of a large-scale liquid xenon TPC in the field of rare event searches.

nucl-ex↗

Seamless Phase 2-3 Design: A Useful Strategy to Reduce the Sample Size for Dose Optimization

The traditional more-is-better dose selection paradigm, developed based on cytotoxic chemotherapeutics, is often problematic When applied to the development of novel molecularly targeted agents (e.g., kinase inhibitors, monoclonal antibodies, and antibody-drug conjugates). The US Food and Drug Administration (FDA) initiated Project Optimus to reform the dose optimization and dose selection paradigm in oncology drug development and call for more attention to benefit-risk consideration. We systematically investigated the operating characteristics of the seamless phase 2-3 design as a strategy for dose optimization, where in stage 1 (corresponding to phase 2) patients are randomized to multiple doses, with or without a control; and in stage 2 (corresponding to phase 3) the efficacy of the selected optimal dose is evaluated with a randomized concurrent control or historical control. Depending on whether the concurrent control is included and the type of endpoints used in stages 1 and 2, we describe four types of seamless phase 2-3 dose-optimization designs, which are suitable for different clinical settings. The statistical and design considerations that pertain to dose optimization are discussed. Simulation shows that dose optimization phase 2-3 designs are able to control the familywise type I error rates and yield appropriate statistical power with substantially smaller sample size than the conventional approach. The sample size savings range from 16.6% to 27.3%, depending on the design and scenario, with a mean savings of 22.1%. Due to the interim dose selection, the phase 2-3 dose-optimization design is logistically and operationally more challenging, and should be carefully planned and implemented to ensure trial integrity.

stat.ME↗

First search for the absorption of fermionic dark matter with the PandaX-4T experiment

Compared with the signature of dark matter elastic scattering off nuclei, the absorption of fermionic dark matter by nuclei opens up a new searching channel for light dark matter with a characteristic monoenergetic signal. In this Letter, we explore the $95.0$-day data from the PandaX-4T commissioning run and report the first dedicated searching results of the fermionic dark matter absorption signal through a neutral current process. No significant signal was found, and the lowest limit on the dark matter-nucleon interaction cross section is set to be $1.5\times10^{-50}$ cm$^2$ for a fermionic dark matter mass of $40$ MeV/$c^2$ with 90\% confidence level.

hep-ex↗

DROID: Dose-ranging Approach to Optimizing Dose in Oncology Drug Development

In the era of targeted therapy, there has been increasing concern about the development of oncology drugs based on the "more is better" paradigm, developed decades ago for chemotherapy. Recently, the US Food and Drug Administration (FDA) initiated Project Optimus to reform the dose optimization and dose selection paradigm in oncology drug development. To accommodate this paradigm shifting, we propose a dose-ranging approach to optimizing dose (DROID) for oncology trials with targeted drugs. DROID leverages the well-established dose-ranging study framework, which has been routinely used to develop non-oncology drugs for decades, and bridges it with established oncology dose-finding designs to optimize the dose of oncology drugs. DROID consists of two seamlessly connected stages. In the first stage, patients are sequentially enrolled and adaptively assigned to investigational doses to establish the therapeutic dose range (TDR), defined as the range of doses with acceptable toxicity and efficacy profiles, and the recommended phase 2 dose set (RP2S). In the second stage, patients are randomized to the doses in RP2S to assess the dose-response relationship and identify the optimal dose. The simulation study shows that DROID substantially outperforms the conventional approach, providing a new paradigm to efficiently optimize the dose of targeted oncology drugs.

stat.ME↗

Neutron-induced nuclear recoil background in the PandaX-4T experiment

Neutron-induced nuclear recoil background is critical to the dark matter searches in the PandaX-4T liquid xenon experiment. This paper studies the feature of neutron background in liquid xenon and evaluates their contribution in the single scattering nuclear recoil events through three methods. The first method is fully Monte Carlo simulation based. The last two are data-driven methods that also use the multiple scattering signals and high energy signals in the data, respectively. In the PandaX-4T commissioning data with an exposure of 0.63 tonne-year, all these methods give a consistent result that there are $1.15\pm0.57$ neutron-induced background in dark matter signal region within an approximated nuclear recoil energy window between 5 and 100 keV.

hep-ex↗

Study of background from accidental coincidence signals in the PandaX-II experiment

The PandaX-II experiment employed a 580kg liquid xenon detector to search for the interactions between dark matter particles and the target xenon atoms. The accidental coincidences of isolated signals result in a dangerous background which mimic the signature of the dark matter. We performed a detailed study on the accidental coincidence background in PandaX-II, including the possible origin of the isolated signals, the background level and corresponding background suppression method. With a boosted-decision-tree algorithm, the accidental coincidence background is reduced by 70% in the dark matter signal region, thus the sensitivity of dark matter search at PandaX-II is improved.

hep-ex↗

A search for two-component Majorana dark matter in a simplified model using the full exposure data of PandaX-II experiment

In the two-component Majorana dark matter model, one dark matter particle can scatter off the target nuclei, and turn into a slightly heavier component. In the framework of a simplified model with a vector boson mediator, both the tree-level and loop-level processes contribute to the signal in direct detection experiment. In this paper, we report the search results for such dark matter from PandaX-II experiment, using total data of the full 100.7 tonne$\cdot$day exposure. No significant excess is observed, so strong constraints on the combined parameter space of mediator mass and dark matter mass are derived. With the complementary search results from collider experiments, a large range of parameter space can be excluded.

hep-ex↗

Low Radioactive Material Screening and Background Control for the PandaX-4T Experiment

PandaX-4T is a ton-scale dark matter direct detection experiment using a dual-phase TPC technique at the China Jinping Underground Laboratory. Various ultra-low background technologies have been developed and applied to material screening for PandaX-4T, including HPGe gamma spectroscopy, ICP-MS, NAA, radon emanation measurement system, krypton assay station, and alpha detection system. Low background materials were selected to assemble the detector. Surface treatment procedures were investigated to further suppress radioactive background. Combining measured results and Monte Carlo simulation, the total material background rates of PandaX-4T in the energy region of 1-25 keV$\rm{}_{ee}$ are estimated to be (9.9 $\pm$ 1.9) $\times \ 10^{-3}$ mDRU for electron recoil and (2.8 $\pm$ 0.6) $\times \ 10^{-4}$ mDRU for nuclear recoil. In addition, $^{nat}$Kr in the detector is estimated to be <8 ppt.

physics.ins-det↗

A Search for the Cosmic Ray Boosted Sub-GeV Dark Matter at the PandaX-II Experiment

We report a novel search for the cosmic ray boosted dark matter using the 100~tonne$\cdot$day full data set of the PandaX-II detector located at the China Jinping Underground Laboratory. With the extra energy gained from the cosmic rays, sub-GeV dark matter particles can produce visible recoil signals in the detector. The diurnal modulations in rate and energy spectrum are utilized to further enhance the signal sensitivity. Our result excludes the dark matter-nucleon elastic scattering cross section between 10$^{-31}$cm$^{2}$ and 10$^{-28}$cm$^{2}$ for a dark matter masses from 0.1 MeV/$c^2$ to 0.1 GeV/$c^2$, with a large parameter space previously unexplored by experimental collaborations.

hep-ex↗

BOP2-DC: Bayesian optimal phase II designs with dual-criterion decision making

The conventional phase II trial design paradigm is to make the go/no-go decision based on the hypothesis testing framework. Statistical significance itself alone, however, may not be sufficient to establish that the drug is clinically effective enough to warrant confirmatory phase III trials. We propose the Bayesian optimal phase II trial design with dual-criterion decision making (BOP2-DC), which incorporates both statistical significance and clinical relevance into decision making. Based on the posterior probability that the treatment effect reaches the lower reference value (statistical significance) and the clinically meaningful value (clinical significance), BOP2-DC allows for go/consider/no-go decisions, rather than a binary go/no-go decision, and it is optimized to maximize the probability of a go decision when the treatment is effective or minimize the sample size when the treatment is futile. BOP2-DC is highly flexible and accommodates various types of endpoints, including binary, continuous, time-to-event, multiple, and co-primary endpoints, in single-arm and randomized trials. Simulation studies show that the BOP2-DC design yields desirable operating characteristics. The software to implement BOP2-DC is freely available at \url{www.trialdesign.org}.

stat.ME↗

Dark Matter Search Results from the PandaX-4T Commissioning Run

We report the first dark matter search results using the commissioning data from PandaX-4T. Using a time projection chamber with 3.7-tonne of liquid xenon target and an exposure of 0.63 tonne$\cdot$year, 1058 candidate events are identified within an approximate nuclear recoil energy window between 5 and 100 keV. No significant excess over background is observed. Our data set a stringent limit to the dark matter-nucleon spin-independent interactions, with a lowest excluded cross section (90% C.L.) of $3.8\times10^{-47} $cm$^2$ at a dark matter mass of 30 GeV/$c^2$.

hep-ex↗

Light yield and field dependence measurement in PandaX-II dual-phase xenon detector

The dual-phase xenon time projection chamber (TPC) is one of the most sensitive detector technology for dark matter direct search, where the energy deposition of incoming particle can be converted into photons and electrons through xenon excitation and ionization. The detector response to signal energy deposition varies significantly with the electric field in liquid xenon. We study the detector's light yield and its dependence on the electric field in the PandaX-II dual-phase detector containing 580~kg liquid xenon in the sensitive volume. From our measurements, the light yield at electric fields from 0~V/cm to 317~V/cm is obtained for energy depositions up to 236~keV.

physics.ins-det↗