arXiv subjects

Joseph G. Ibrahim

Publications and source records attributed to Joseph G. Ibrahim.

At least 19 recordsLinked to original sources

arXiv2026

From priors to performance: enhancing statistical efficiency with Bayesian dynamic borrowing

One of the main advantages of the Bayesian approach to statistical inference is the flexibility in incorporating information from various sources, from expert opinion to historical data. Whereas the literature on Bayesian dynamic borrowing is rich, practical guidance for how to implement such methods is comparatively sparse. We thoroughly review the most common dynamic borrowing approaches for external data, including how to incorporate multiple historical data sets. We then show how these techniques can be used in practice, using publicly available software, to perform important statistical tasks such as model selection, average treatment effect estimation and prior sensitivity analysis. The aim is to make analysts more confident in their use of Bayesian methods to incorporate external data. All code is made publicly available in a companion GitHub repository (https://github.com/EzequielEBS/hdbayes-tutorial).

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arXiv2025

Cure Rate Joint Model for Time-to-Event Data and Longitudinal Tumor Burden with Potential Change Points

In non-small cell lung cancer (NSCLC) clinical trials, tumor burden (TB) is a key longitudinal biomarker for assessing treatment effects. Typically, standard-of-care (SOC) therapies and some novel interventions initially decrease TB; however, many patients subsequently experience an increase-indicating disease progression-while others show a continuous decline. In patients with an eventual TB increase, the change point marks the onset of progression and must occur before the time of the event. To capture these distinct dynamics, we propose a novel joint model that integrates time-to-event and longitudinal TB data, classifying patients into a change-point group or a stable group. For the change-point group, our approach flexibly estimates an individualized change point by leveraging time-to-event information. We use a Monte Carlo Expectation-Maximization (MCEM) algorithm for efficient parameter estimation. Simulation studies demonstrate that our model outperforms traditional approaches by accurately capturing diverse disease progression patterns and handling censoring complexities, leading to robust marginal TB outcome estimates. When applied to a Phase 3 NSCLC trial comparing cemiplimab monotherapy to SOC, the treatment group shows prolonged TB reduction and consistently lower TB over time, highlighting the clinical utility of our approach. The implementation code is publicly available on https://github.com/quyixiang/JoCuR.

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arXiv2025

hdbayes: An R Package for Bayesian Analysis of Generalized Linear Models Using Historical Data

There has been increased interest in the use of historical data to formulate informative priors in regression models. While many such priors for incorporating historical data have been proposed, adoption is limited due to access to software. Where software does exist, the implementations between different methods could be vastly different, making comparisons between methods difficult. In this paper, we introduce the R package hdbayes, an implementation of the power prior, normalized power prior, Bayesian hierarchical model, robust meta-analytic prior, commensurate prior, and latent exchangeability prior for generalized linear models. The bulk of the package is written in the Stan programming language, with user-friendly R wrapper functions to call samplers.

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arXiv2025

ANPP: the Adapted Normalized Power Prior for Borrowing Information from Multiple Historical Datasets in Clinical Trials

The power prior is a popular class of informative priors for incorporating information from historical data. It involves raising the likelihood for the historical data to a power, which acts as a discounting parameter. When the discounting parameter is modeled as random, the normalized power prior (NPP) is recommended. When there are multiple historical datasets, there has been limited research on how to choose priors for the multiple discounting parameters of the NPP to induce desirable information borrowing behavior. In this work, we address this question by investigating the analytical relationship between the NPP and the Bayesian hierarchical model (BHM), which is a widely used method for synthesizing information from different sources. We develop the adapted normalized power prior (ANPP), which establishes dependence between the dataset-specific discounting parameters of the NPP, leading to inferences that are identical to the BHM. We establish a direct relationship between the prior for the dataset-specific discounting parameters of the ANPP and the prior for the variance parameter of the BHM. Establishing this relationship not only justifies the NPP from the perspective of hierarchical modeling, but also achieves easy prior elicitation for the NPP for the purpose of dynamic borrowing. We examine the borrowing properties of the ANPP through simulations, and apply it to a case study for a pediatric lupus trial.

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arXiv2025

Residual-based Alternative Partial Least Squares for Generalized Functional Linear Models

Many biomedical studies collect high-dimensional medical imaging data to identify biomarkers for the detection, diagnosis, and treatment of human diseases. Consequently, it is crucial to develop accurate models that can predict a wide range of clinical outcomes (both discrete and continuous) based on imaging data. By treating imaging predictors as functional data, we propose a residual-based alternative partial least squares (RAPLS) model for a broad class of generalized functional linear models that incorporate both functional and scalar covariates. Our RAPLS method extends the alternative partial least squares (APLS) algorithm iteratively to accommodate additional scalar covariates and non-continuous outcomes. We establish the convergence rate of the RAPLS estimator for the unknown slope function and, with an additional calibration step, we prove the asymptotic normality and efficiency of the calibrated RAPLS estimator for the scalar parameters. The effectiveness of the RAPLS algorithm is demonstrated through multiple simulation studies and an application predicting Alzheimer's disease progression using neuroimaging data from the Alzheimer's Disease Neuroimaging Initiative (ADNI).

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arXiv2024

Jointly modeling time-to-event and longitudinal data with individual-specific change points: a case study in modeling tumor burden

In oncology clinical trials, tumor burden (TB) stands as a crucial longitudinal biomarker, reflecting the toll a tumor takes on a patient's prognosis. With certain treatments, the disease's natural progression shows the tumor burden initially receding before rising once more. Biologically, the point of change may be different between individuals and must have occurred between the baseline measurement and progression time of the patient, implying a random effects model obeying a bound constraint. However, in practice, patients may drop out of the study due to progression or death, presenting a non-ignorable missing data problem. In this paper, we introduce a novel joint model that combines time-to-event data and longitudinal data, where the latter is parameterized by a random change point augmented by random pre-slope and post-slope dynamics. Importantly, the model is equipped to incorporate covariates across for the longitudinal and survival models, adding significant flexibility. Adopting a Bayesian approach, we propose an efficient Hamiltonian Monte Carlo algorithm for parameter inference. We demonstrate the superiority of our approach compared to a longitudinal-only model via simulations and apply our method to a data set in oncology.

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arXiv2024

Efficient Computation of High-Dimensional Penalized Generalized Linear Mixed Models by Latent Factor Modeling of the Random Effects

Modern biomedical datasets are increasingly high dimensional and exhibit complex correlation structures. Generalized Linear Mixed Models (GLMMs) have long been employed to account for such dependencies. However, proper specification of the fixed and random effects in GLMMs is increasingly difficult in high dimensions, and computational complexity grows with increasing dimension of the random effects. We present a novel reformulation of the GLMM using a factor model decomposition of the random effects, enabling scalable computation of GLMMs in high dimensions by reducing the latent space from a large number of random effects to a smaller set of latent factors. We also extend our prior work to estimate model parameters using a modified Monte Carlo Expectation Conditional Minimization algorithm, allowing us to perform variable selection on both the fixed and random effects simultaneously. We show through simulation that through this factor model decomposition, our method can fit high dimensional penalized GLMMs faster than comparable methods and more easily scale to larger dimensions not previously seen in existing approaches.

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arXiv2024

glmmPen: High Dimensional Penalized Generalized Linear Mixed Models

Generalized linear mixed models (GLMMs) are widely used in research for their ability to model correlated outcomes with non-Gaussian conditional distributions. The proper selection of fixed and random effects is a critical part of the modeling process since model misspecification may lead to significant bias. However, the joint selection of fixed and random effects has historically been limited to lower-dimensional GLMMs, largely due to the use of criterion-based model selection strategies. Here we present the R package glmmPen, one of the first to select fixed and random effects in higher dimension using a penalized GLMM modeling framework. Model parameters are estimated using a Monte Carlo Expectation Conditional Minimization (MCECM) algorithm, which leverages Stan and RcppArmadillo for increased computational efficiency. Our package supports the Binomial, Gaussian, and Poisson families and multiple penalty functions. In this manuscript we discuss the modeling procedure, estimation scheme, and software implementation through application to a pancreatic cancer subtyping study. Simulation results show our method has good performance in selecting both the fixed and random effects in high dimensional GLMMs.

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arXiv2024

Optimal Priors for the Discounting Parameter of the Normalized Power Prior

The power prior is a popular class of informative priors for incorporating information from historical data. It involves raising the likelihood for the historical data to a power, which acts as discounting parameter. When the discounting parameter is modelled as random, the normalized power prior is recommended. In this work, we prove that the marginal posterior for the discounting parameter for generalized linear models converges to a point mass at zero if there is any discrepancy between the historical and current data, and that it does not converge to a point mass at one when they are fully compatible. In addition, we explore the construction of optimal priors for the discounting parameter in a normalized power prior. In particular, we are interested in achieving the dual objectives of encouraging borrowing when the historical and current data are compatible and limiting borrowing when they are in conflict. We propose intuitive procedures for eliciting the shape parameters of a beta prior for the discounting parameter based on two minimization criteria, the Kullback-Leibler divergence and the mean squared error. Based on the proposed criteria, the optimal priors derived are often quite different from commonly used priors such as the uniform prior.

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arXiv2024

BayesPPDSurv: An R Package for Bayesian Sample Size Determination Using the Power and Normalized Power Prior for Time-To-Event Data

The BayesPPDSurv (Bayesian Power Prior Design for Survival Data) R package supports Bayesian power and type I error calculations and model fitting using the power and normalized power priors incorporating historical data with for the analysis of time-to-event outcomes. The package implements the stratified proportional hazards regression model with piecewise constant hazard within each stratum. The package allows the historical data to inform the treatment effect parameter, parameter effects for other covariates in the regression model, as well as the baseline hazard parameters. The use of multiple historical datasets is supported. A novel algorithm is developed for computationally efficient use of the normalized power prior. In addition, the package supports the use of arbitrary sampling priors for computing Bayesian power and type I error rates, and has built-in features that semi-automatically generate sampling priors from the historical data. We demonstrate the use of BayesPPDSurv in a comprehensive case study for a melanoma clinical trial design.

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arXiv2023

LEAP: The latent exchangeability prior for borrowing information from historical data

It is becoming increasingly popular to elicit informative priors on the basis of historical data. Popular existing priors, including the power prior, commensurate prior, and robust meta-analytic prior provide blanket discounting. Thus, if only a subset of participants in the historical data are exchangeable with the current data, these priors may not be appropriate. In order to combat this issue, propensity score (PS) approaches have been proposed. However, PS approaches are only concerned with the covariate distribution, whereas exchangeability is typically assessed with parameters pertaining to the outcome. In this paper, we introduce the latent exchangeability prior (LEAP), where observations in the historical data are classified into exchangeable and non-exchangeable groups. The LEAP discounts the historical data by identifying the most relevant subjects from the historical data. We compare our proposed approach against alternative approaches in simulations and present a case study using our proposed prior to augment a control arm in a phase 3 clinical trial in plaque psoriasis with an unbalanced randomization scheme.

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arXiv2022

Unsupervised Imputation of Non-ignorably Missing Data Using Importance-Weighted Autoencoders

Deep Learning (DL) methods have dramatically increased in popularity in recent years. While its initial success was demonstrated in the classification and manipulation of image data, there has been significant growth in the application of DL methods to problems in the biomedical sciences. However, the greater prevalence and complexity of missing data in biomedical datasets present significant challenges for DL methods. Here, we provide a formal treatment of missing data in the context of Variational Autoencoders (VAEs), a popular unsupervised DL architecture commonly utilized for dimension reduction, imputation, and learning latent representations of complex data. We propose a new VAE architecture, NIMIWAE, that is one of the first to flexibly account for both ignorable and non-ignorable patterns of missingness in input features at training time. Following training, samples can be drawn from the approximate posterior distribution of the missing data can be used for multiple imputation, facilitating downstream analyses on high dimensional incomplete datasets. We demonstrate through statistical simulation that our method outperforms existing approaches for unsupervised learning tasks and imputation accuracy. We conclude with a case study of an EHR dataset pertaining to 12,000 ICU patients containing a large number of diagnostic measurements and clinical outcomes, where many features are only partially observed.

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arXiv2021

BayesPPD: An R Package for Bayesian Sample Size Determination Using the Power and Normalized Power Prior for Generalized Linear Models

The R package BayesPPD (Bayesian Power Prior Design) supports Bayesian power and type I error calculation and model fitting after incorporating historical data with the power prior and the normalized power prior for generalized linear models (GLM). The package accommodates summary level data or subject level data with covariate information. It supports use of multiple historical datasets as well as design without historical data. Supported distributions for responses include normal, binary (Bernoulli/binomial), Poisson and exponential. The power parameter $a_0$ can be fixed or modeled as random using a normalized power prior for each of these distributions. In addition, the package supports the use of arbitrary sampling priors for computing Bayesian power and type I error rates, and has specific features for GLMs that semi-automatically generate sampling priors from historical data. Since sample size determination (SSD) for GLMs is computationally intensive, an approximation method based on asymptotic theory has been implemented to support applications using the power prior. In addition to describing the statistical methodology and functions implemented in the package to enable SSD, we also demonstrate the use of BayesPPD in two comprehensive case studies.

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arXiv2021

A hierarchical prior for generalized linear models based on predictions for the mean response

There has been increased interest in using prior information in statistical analyses. For example, in rare diseases, it can be difficult to establish treatment efficacy based solely on data from a prospective study due to low sample sizes. To overcome this issue, an informative prior for the treatment effect may be elicited. We develop a novel extension of the conjugate prior of Chen and Ibrahim (2003) that enables practitioners to elicit a prior prediction for the mean response for generalized linear models, treating the prediction as random. We refer to the hierarchical prior as the hierarchical prediction prior. For i.i.d. settings and the normal linear model, we derive cases for which the hyperprior is a conjugate prior. We also develop an extension of the HPP in situations where summary statistics from a previous study are available, drawing comparisons with the power prior. The HPP allows for discounting based on the quality of individual level predictions, having the potential to provide efficiency gains (e.g., lower MSE) where predictions are incompatible with the data. An efficient Markov chain Monte Carlo algorithm is developed. Applications illustrate that inferences under the HPP are more robust to prior-data conflict compared to selected non-hierarchical priors.

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arXiv2021

The scale transformed power prior for use with historical data from a different outcome model

We develop the scale transformed power prior for settings where historical and current data involve different data types, such as binary and continuous data, respectively. This situation arises often in clinical trials, for example, when historical data involve binary responses and the current data involve time-to-event or some other type of continuous or discrete outcome. The power prior proposed by Ibrahim and Chen (2000) does not address the issue of different data types. Herein, we develop a new type of power prior, which we call the scale transformed power prior (straPP). The straPP is constructed by transforming the power prior for the historical data by rescaling the parameter using a function of the Fisher information matrices for the historical and current data models, thereby shifting the scale of the parameter vector from that of the historical to that of the current data. Examples are presented to motivate the need for a scale transformation and simulation studies are presented to illustrate the performance advantages of the straPP over the power prior and other informative and non-informative priors. A real dataset from a clinical trial undertaken to study a novel transitional care model for stroke survivors is used to illustrate the methodology.

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arXiv2020

Bayesian Multivariate Probability of Success Using Historical Data with Strict Control of Family-wise Error Rate

Given the cost and duration of phase III and phase IV clinical trials, the development of statistical methods for go/no-go decisions is vital. In this paper, we introduce a Bayesian methodology to compute the probability of success based on the current data of a treatment regimen for the multivariate linear model. Our approach utilizes a Bayesian seemingly unrelated regression model, which allows for multiple endpoints to be modeled jointly even if the covariates between the endpoints are different. Correlations between endpoints are explicitly modeled. This Bayesian joint modeling approach unifies single and multiple testing procedures under a single framework. We develop an approach to multiple testing that asymptotically guarantees strict family-wise error rate control, and is more powerful than frequentist approaches to multiplicity. The method effectively yields those of Ibrahim et al. and Chuang-Stein as special cases, and, to our knowledge, is the only method that allows for robust sample size determination for multiple endpoints and/or hypotheses and the only method that provides strict family-wise type I error control in the presence of multiplicity.

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arXiv2020

On the normalized power prior

The power prior is a popular tool for constructing informative prior distributions based on historical data. The method consists of raising the likelihood to a discounting factor in order to control the amount of information borrowed from the historical data. It is customary to perform a sensitivity analysis reporting results for a range of values of the discounting factor. However, one often wishes to assign it a prior distribution and estimate it jointly with the parameters, which in turn necessitates the computation of a normalising constant. In this paper we are concerned with how to recycle computations from a sensitivity analysis in order to approximately sample from joint posterior of the parameters and the discounting factor. We first show a few important properties of the normalising constant and then use these results to motivate a bisection-type algorithm for computing it on a fixed budget of evaluations. We give a large array of illustrations and discuss cases where the normalising constant is known in closed-form and where it is not. We show that the proposed method produces approximate posteriors that are very close to the exact distributions when those are available and also produces posteriors that cover the data-generating parameters with higher probability in the intractable case. Our results show that proper inclusion the normalising constant is crucial to the correct quantification of uncertainty and that the proposed method is an accurate and easy to implement technique to include this normalisation, being applicable to a large class of models. Key-words: Doubly-intractable; elicitation; historical data; normalisation; power prior; sensitivity analysis.

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arXiv2019

Modeling Between-Study Heterogeneity for Improved Reproducibility in Gene Signature Selection and Clinical Prediction

In the genomic era, the identification of gene signatures associated with disease is of significant interest. Such signatures are often used to predict clinical outcomes in new patients and aid clinical decision-making. However, recent studies have shown that gene signatures are often not replicable. This occurrence has practical implications regarding the generalizability and clinical applicability of such signatures. To improve replicability, we introduce a novel approach to select gene signatures from multiple datasets whose effects are consistently non-zero and account for between-study heterogeneity. We build our model upon some rank-based quantities, facilitating integration over different genomic datasets. A high dimensional penalized Generalized Linear Mixed Model (pGLMM) is used to select gene signatures and address data heterogeneity. We compare our method to some commonly used strategies that select gene signatures ignoring between-study heterogeneity. We provide asymptotic results justifying the performance of our method and demonstrate its advantage in the presence of heterogeneity through thorough simulation studies. Lastly, we motivate our method through a case study subtyping pancreatic cancer patients from four gene expression studies.

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