Journal of the Royal Statistical Society Series C: Applied Statistics
We propose an adaptive hybrid control causal (AHCC) design to leverage historical control data to... more We propose an adaptive hybrid control causal (AHCC) design to leverage historical control data to reduce the sample size demanded by standard randomised controlled trials (RCT). Under the causal inference framework, we define the causal estimand of the average treatment effect and derive the corresponding estimator based on the trial data and historical control data. The AHCC design takes a multistage or group sequential approach. The number of patients randomised to the concurrent control is adaptively adjusted based on the amount of information borrowed from the historical control data. At each stage, based on the interim data, the contribution of the historical control data, quantified by the effective sample size, is updated and used to determine the randomisation ratio between the treatment and control arms for the next stage, with the goal to resemble a standard RCT upon the completion of the trial. Simulation studies show that the AHCC design has desirable operating character...
Existing phase II clinical trial designs focus on a single scalar endpoint, such as a binary, con... more Existing phase II clinical trial designs focus on a single scalar endpoint, such as a binary, continuous, or survival endpoint. In some clinical trials, such as pain management studies, the efficacy endpoint of interest is measured longitudinally. We propose a Bayesian phase II design for such clinical trials. We model the longitudinal measurement process using Bayesian hierarchical model, where subject‐specific trajectory shrinks toward the population trajectory to borrow information across subjects. The Bayesian penalized spline is used to model subject‐specific and population trajectories without making strong parametric assumption on their shapes. We use the area under the curve of the trajectory as the summary of the treatment effect over time. The design takes a group sequential approach and takes into account both statistical significance and clinical relevance. Bayesian criteria is proposed to make interim and final decisions based on the evidence of statistical significance...
Statistics in Biopharmaceutical Research, Jun 1, 2021
Abstract Traditional vaccine clinical development is an undertaking involving meticulous, multipl... more Abstract Traditional vaccine clinical development is an undertaking involving meticulous, multiple studies in multiple populations at risk of infection and disease over multiple years. SARS-CoV-2 and COVID-19 vaccine development is following this traditional development pathway, and accelerated Phase I-II-III clinical programs are being applied. This is not the first time vaccines have been manufactured and tested quickly to meet a public health crisis. Selected statistical concepts pertaining to vaccine efficacy and safety, relevant during the design and implementation of such clinical development programs, will be discussed.
Industries such as the manufacturing or logistics industry need algorithms that are flexible to h... more Industries such as the manufacturing or logistics industry need algorithms that are flexible to handle novel or unknown objects. Many current solutions in the market are unsuitable for grasping these objects in high-mix and low-volume scenarios. Finally, there are still gaps in terms of grasping accuracy and speed that we would like to address in this research. This project aims to improve the robotic grasping capability for novel objects with varying shapes and textures through the use of soft grippers and data-driven learning in a hyper-personalization line. A literature review was conducted to understand the tradeoffs between the deep reinforcement learning (DRL) approach and the deep learning (DL) approach. The DRL approach was found to be data-intensive, complex, and collision-prone. As a result, we opted for a data-driven approach, which to be more specific, is PointNet GPD in this project. In addition, a comprehensive market survey was performed on tactile sensors and soft gr...
Initial release of the Isabelle/HoTT object logic, coinciding with the submission of my MS thesis... more Initial release of the Isabelle/HoTT object logic, coinciding with the submission of my MS thesis. There is still lots of work to be done, and it is quite likely that future versions will not look very much like the current state. In particular, polymorphism is a pain. Also proof methods.
Even when racially diversified, American organizations remain dominated by whites. The color line... more Even when racially diversified, American organizations remain dominated by whites. The color line regularly reasserts itself through racialized structures and social patterns. Many academics therefore argue that racial integration does not work. However, this argument has two limitations. Theoretically, the argument conflates integration with desegregation. Most diverse institutions are integrated in principle but desegregated in practice. Whereas desegregation dismantles racial barriers to entry, it leaves existing structures unchanged. Integration, by contrast, makes changes that facilitate the structural inclusion of people of color. Empirically, the majority of research is drawn from studies of predominantly white organizations. Theories of colorblind racism show how such organizations can be expected to sustain white hegemony. By contrast, I analyze two years worth of ethnographic, interview, and survey data from two organizations where whites are not dominant: a church in the ...
Supplement_Inconsistency_Examples_26Jun for Lessons Learned From Multi-regional Trials With Signa... more Supplement_Inconsistency_Examples_26Jun for Lessons Learned From Multi-regional Trials With Signals of Treatment Effect Heterogeneity by Gang Li, Hui Quan, Gordon Lan, Soo Peter Ouyang, Fei Chen, Weining Robieson, William Wang, Bruce Binkowitz, Shuai Sammy Yuan, Yoko Tanaka, Josh Chen, Nobushige Matsuoka, Lanju Zhang, Song Yang, and Paul Gallo in Therapeutic Innovation & Regulatory Science
Abstract Traditional vaccine clinical development is an undertaking involving meticulous, multipl... more Abstract Traditional vaccine clinical development is an undertaking involving meticulous, multiple studies in multiple populations at risk of infection and disease over multiple years. SARS-CoV-2 and COVID-19 vaccine development is following this traditional development pathway, and accelerated Phase I-II-III clinical programs are being applied. This is not the first time vaccines have been manufactured and tested quickly to meet a public health crisis. Selected statistical concepts pertaining to vaccine efficacy and safety, relevant during the design and implementation of such clinical development programs, will be discussed.
Drugs that alter ventricular repolarization have been associated with malignant ventricular arrhy... more Drugs that alter ventricular repolarization have been associated with malignant ventricular arrhythmia, which has been shown to increase with increasing QT interval—the time required for ventricular depolarization and repolarization. To determine whether a new drug, especially a nonanti-arrhythmia drug, can cause an increase in the QT interval is a necessary step in safety evaluation. Since the QT interval is inversely
Journal of the Royal Statistical Society Series C: Applied Statistics
We propose an adaptive hybrid control causal (AHCC) design to leverage historical control data to... more We propose an adaptive hybrid control causal (AHCC) design to leverage historical control data to reduce the sample size demanded by standard randomised controlled trials (RCT). Under the causal inference framework, we define the causal estimand of the average treatment effect and derive the corresponding estimator based on the trial data and historical control data. The AHCC design takes a multistage or group sequential approach. The number of patients randomised to the concurrent control is adaptively adjusted based on the amount of information borrowed from the historical control data. At each stage, based on the interim data, the contribution of the historical control data, quantified by the effective sample size, is updated and used to determine the randomisation ratio between the treatment and control arms for the next stage, with the goal to resemble a standard RCT upon the completion of the trial. Simulation studies show that the AHCC design has desirable operating character...
Existing phase II clinical trial designs focus on a single scalar endpoint, such as a binary, con... more Existing phase II clinical trial designs focus on a single scalar endpoint, such as a binary, continuous, or survival endpoint. In some clinical trials, such as pain management studies, the efficacy endpoint of interest is measured longitudinally. We propose a Bayesian phase II design for such clinical trials. We model the longitudinal measurement process using Bayesian hierarchical model, where subject‐specific trajectory shrinks toward the population trajectory to borrow information across subjects. The Bayesian penalized spline is used to model subject‐specific and population trajectories without making strong parametric assumption on their shapes. We use the area under the curve of the trajectory as the summary of the treatment effect over time. The design takes a group sequential approach and takes into account both statistical significance and clinical relevance. Bayesian criteria is proposed to make interim and final decisions based on the evidence of statistical significance...
Statistics in Biopharmaceutical Research, Jun 1, 2021
Abstract Traditional vaccine clinical development is an undertaking involving meticulous, multipl... more Abstract Traditional vaccine clinical development is an undertaking involving meticulous, multiple studies in multiple populations at risk of infection and disease over multiple years. SARS-CoV-2 and COVID-19 vaccine development is following this traditional development pathway, and accelerated Phase I-II-III clinical programs are being applied. This is not the first time vaccines have been manufactured and tested quickly to meet a public health crisis. Selected statistical concepts pertaining to vaccine efficacy and safety, relevant during the design and implementation of such clinical development programs, will be discussed.
Industries such as the manufacturing or logistics industry need algorithms that are flexible to h... more Industries such as the manufacturing or logistics industry need algorithms that are flexible to handle novel or unknown objects. Many current solutions in the market are unsuitable for grasping these objects in high-mix and low-volume scenarios. Finally, there are still gaps in terms of grasping accuracy and speed that we would like to address in this research. This project aims to improve the robotic grasping capability for novel objects with varying shapes and textures through the use of soft grippers and data-driven learning in a hyper-personalization line. A literature review was conducted to understand the tradeoffs between the deep reinforcement learning (DRL) approach and the deep learning (DL) approach. The DRL approach was found to be data-intensive, complex, and collision-prone. As a result, we opted for a data-driven approach, which to be more specific, is PointNet GPD in this project. In addition, a comprehensive market survey was performed on tactile sensors and soft gr...
Initial release of the Isabelle/HoTT object logic, coinciding with the submission of my MS thesis... more Initial release of the Isabelle/HoTT object logic, coinciding with the submission of my MS thesis. There is still lots of work to be done, and it is quite likely that future versions will not look very much like the current state. In particular, polymorphism is a pain. Also proof methods.
Even when racially diversified, American organizations remain dominated by whites. The color line... more Even when racially diversified, American organizations remain dominated by whites. The color line regularly reasserts itself through racialized structures and social patterns. Many academics therefore argue that racial integration does not work. However, this argument has two limitations. Theoretically, the argument conflates integration with desegregation. Most diverse institutions are integrated in principle but desegregated in practice. Whereas desegregation dismantles racial barriers to entry, it leaves existing structures unchanged. Integration, by contrast, makes changes that facilitate the structural inclusion of people of color. Empirically, the majority of research is drawn from studies of predominantly white organizations. Theories of colorblind racism show how such organizations can be expected to sustain white hegemony. By contrast, I analyze two years worth of ethnographic, interview, and survey data from two organizations where whites are not dominant: a church in the ...
Supplement_Inconsistency_Examples_26Jun for Lessons Learned From Multi-regional Trials With Signa... more Supplement_Inconsistency_Examples_26Jun for Lessons Learned From Multi-regional Trials With Signals of Treatment Effect Heterogeneity by Gang Li, Hui Quan, Gordon Lan, Soo Peter Ouyang, Fei Chen, Weining Robieson, William Wang, Bruce Binkowitz, Shuai Sammy Yuan, Yoko Tanaka, Josh Chen, Nobushige Matsuoka, Lanju Zhang, Song Yang, and Paul Gallo in Therapeutic Innovation & Regulatory Science
Abstract Traditional vaccine clinical development is an undertaking involving meticulous, multipl... more Abstract Traditional vaccine clinical development is an undertaking involving meticulous, multiple studies in multiple populations at risk of infection and disease over multiple years. SARS-CoV-2 and COVID-19 vaccine development is following this traditional development pathway, and accelerated Phase I-II-III clinical programs are being applied. This is not the first time vaccines have been manufactured and tested quickly to meet a public health crisis. Selected statistical concepts pertaining to vaccine efficacy and safety, relevant during the design and implementation of such clinical development programs, will be discussed.
Drugs that alter ventricular repolarization have been associated with malignant ventricular arrhy... more Drugs that alter ventricular repolarization have been associated with malignant ventricular arrhythmia, which has been shown to increase with increasing QT interval—the time required for ventricular depolarization and repolarization. To determine whether a new drug, especially a nonanti-arrhythmia drug, can cause an increase in the QT interval is a necessary step in safety evaluation. Since the QT interval is inversely
Uploads
Papers by Josh Chen