Precision medicine Bayesian Statistics

Identifying predictive factors for an outcome of interest via a multivariable analysis is often difficult when the data set is small. Combining data from different medical centers into a single (larger) database would alleviate this problem, but is in practice challenging due to regulatory and logistic problems. Federated learning (FL) is a machine learning approach that aims to construct from local inferences in separate data centers what would have been inferred had the data sets been merged. It seeks to harvest the statistical power of larger data sets without actually creating them...

BACKGROUND: The prospective cohort study PROTECT is the largest study in pediatric ulcerative colitis (UC) with standardized treatments, providing valuable data for predicting clinical outcomes. PROTECT and previous studies have identified characteristics associated with clinical outcomes. In this study, we aimed to compare predictive modeling between Bayesian analysis including machine learning and frequentist analysis. METHODS: The key outcomes for this analysis were week 4, 12 and 52 corticosteroid (CS)-free remission following standardized treatment from diagnosis...

The Birnbaum-Saunders distribution plays a crucial role in statistical analysis, serving as a model for failure time distribution in engineering and the distribution of particulate matter 2.5 (PM2.5) in environmental sciences. When assessing the health risks linked to PM2.5, it is crucial to give significant weight to percentile values, particularly focusing on lower percentiles, as they offer a more precise depiction of exposure levels and potential health hazards for the population. Mean and variance metrics may not fully encapsulate the comprehensive spectrum of risks connected to PM2...

Precision medicine is a promising framework for generating evidence to improve health and health care. Yet, a gap persists between the ever-growing number of statistical precision medicine strategies for evidence generation and implementation in real-world clinical settings, and the strategies for closing this gap will likely be context-dependent. In this paper, we consider the specific context of partial compliance to wound management among patients with peripheral artery disease. Using a Gaussian process surrogate for the value function, we show the feasibility of using Bayesian optimization to learn optimal individualized treatment rules...

Combination antiretroviral therapy (ART) with at least three different drugs has become the standard of care for people with HIV (PWH) due to its exceptional effectiveness in viral suppression. However, many ART drugs have been reported to associate with neuropsychiatric adverse effects including depression, especially when certain genetic polymorphisms exist. Pharmacogenetics is an important consideration for administering combination ART as it may influence drug efficacy and increase risk for neuropsychiatric conditions...

This study presents a comprehensive analysis of historical fire and climatic data to estimate the monthly frequency of vegetation fires in Kenya. This work introduces a statistical model that captures the behavior of fire count data, incorporating temporal explanatory factors and emphasizing the predictive significance of maximum temperature and rainfall. By employing Bayesian approaches, the paper integrates literature information, simulation studies, and real-world data to enhance model performance and generate more precise prediction intervals that encompass actual fire counts...

Recently, many studies have addressed the performance of phylogenetic tree-building methods (maximum parsimony, maximum likelihood, and Bayesian inference), focusing primarily on simulated data. However, for discrete morphological data, there is no consensus yet on which methods recover the phylogeny with better performance. To address this lack of consensus, we investigate the performance of different methods using an empirical dataset for hexapods as a model. As an empirical test of performance, we applied normalized indices to effectively measure accuracy (normalized Robinson-Foulds metric, nRF) and precision, which are measured via resolution, one minus Colless' consensus fork index (1-CFI)...

Background: The introduction of foods or fluids other than breast milk in the first few days after birth interferes with the establishment of breastfeeding. This study aimed to investigate the association of formula introduction during the first 3 days of life with maternal sociodemographic characteristics, hospital practices, and breastfeeding duration. Materials and Methods: Information from the National Survey of Demographic Dynamics, 2018, which includes 17,686 mother-baby pairs was analyzed. Mother-baby pairs were classified into categories according to breastfeeding duration: <5 months and ≥5 months...

BACKGROUND: The initiation biomarker-driven trials have revolutionized oncology drug development by challenging the traditional phased approach and introducing basket studies. Notable successes in non-small cell lung cancer (NSCLC) with ALK, ALK/ROS1, and EGFR inhibitors have prompted the need to expand this approach to other cancer sites. OBJECTIVES: This study explores the use of dose response modeling and time-to-event algorithms on the biomarker molecular targeted agent (MTA)...

In the recent JAVELIN Bladder 100 phase 3 trial, avelumab plus best supportive care significantly prolonged overall survival relative to best supportive care alone as first-line maintenance therapy following first-line platinum-based chemotherapy in patients with advanced urothelial cancer (aUC). Discovering biomarkers using genomic profiling to understand potential patient heterogeneity is essential to help improve patient care with precision medicine. For the JAVELIN Bladder 100 trial, it is unclear which variable selection methods can most reliably identify biomarkers to inform patient care because the dataset is characterized by high collinearity and low signal...

PURPOSE: In metastatic colorectal cancer, the detection of RAS mutations by circulating tumor DNA (ctDNA) has emerged as a valid and noninvasive alternative approach to determining RAS status. However, some RAS mutations may be missed, that is, false negatives can occur, possibly compromising important treatment decisions. We propose a statistical model to assess the probability of false negatives when performing ctDNA testing for RAS. METHODS: Cohorts of 172 subjects with tissue and multipanel ctDNA testing from MD Anderson Cancer Center and 146 subjects from Massachusetts General Hospital were collected...

Antibiotic use is becoming increasingly challenging with the emergence of multidrug-resistant organisms. Pharmacokinetic (PK) alterations result from complex pathophysiologic changes in some patient populations, particularly those with critical illness. Therefore, antibiotic dose individualization in such populations is warranted. Recently, there have been advances in dose optimization strategies to improve the utilization of existing antibiotics. Bayesian-based dosing is one of the novel approaches that could help clinicians achieve target concentrations in a greater percentage of their patients earlier during therapy...

Accurate identification of synergistic treatment combinations and their underlying biological mechanisms is critical across many disease domains, especially cancer. In translational oncology research, preclinical systems such as patient-derived xenografts (PDX) have emerged as a unique study design evaluating multiple treatments administered to samples from the same human tumor implanted into genetically identical mice. In this paper, we propose a novel Bayesian probabilistic tree-based framework for PDX data to investigate the hierarchical relationships between treatments by inferring treatment cluster trees, referred to as treatment trees (Rx -tree)...

Electroencephalography and magnetoencephalography recordings are non-invasive and temporally precise, making them invaluable tools in the investigation of neural responses in humans. However, these recordings are noisy, both because the neuronal electrodynamics involved produces a muffled signal and because the neuronal processes of interest compete with numerous other processes, from blinking to day-dreaming. One fruitful response to this noisiness has been to use stimuli with a specific frequency and to look for the signal of interest in the response at that frequency...

To achieve the goal of providing the best possible care to each individual under their care, physicians need to customize treatments for individuals with the same health state, especially when treating diseases that can progress further and require additional treatments, such as cancer. Making decisions at multiple stages as a disease progresses can be formalized as a dynamic treatment regime (DTR). Most of the existing optimization approaches for estimating dynamic treatment regimes including the popular method of Q-learning were developed in a frequentist context...

Borrowing information from historical or external data to inform inference in a current trial is an expanding field in the era of precision medicine, where trials are often performed in small patient cohorts for practical or ethical reasons. Even though methods proposed for borrowing from external data are mainly based on Bayesian approaches that incorporate external information into the prior for the current analysis, frequentist operating characteristics of the analysis strategy are often of interest. In particular, type I error rate and power at a prespecified point alternative are the focus...

Recent innovation in trial design to improve study efficiency has led to the development of basket trials in which a single therapeutic treatment is tested on several patient populations, each of which forms a basket. In a common setting, patients across all baskets share a genetic marker and as such, an assumption can be made that all patients may have a homogeneous response to treatments. Bayesian information borrowing procedures utilize this assumption to draw on information regarding the response in one basket when estimating the response rate in others...

The Glasgow outcome scale-extended (GOS-E), an ordinal scale measure, is often selected as the endpoint for clinical trials of traumatic brain injury (TBI). Traditionally, GOS-E is analyzed as a fixed dichotomy with favorable outcome defined as GOS-E ≥ 5 and unfavorable outcome as GOS-E < 5. More recent studies have defined favorable vs unfavorable outcome utilizing a sliding dichotomy of the GOS-E that defines a favorable outcome as better than a subject's predicted prognosis at baseline...

In the era of precision medicine, many biomarkers have been discovered to be associated with drug efficacy and safety responses, which can be used for patient stratification and drug response prediction. Due to the small sample size and limited power of randomized clinical studies, meta-analysis is usually conducted to aggregate all available studies to maximize the power for identifying prognostic and predictive biomarkers. However, it is often challenging to find an independent study to replicate the discoveries from the meta-analysis (e...

BACKGROUND: Predicting protein levels from genotypes for proteome-wide association studies (PWAS) may provide insight into the mechanisms underlying cancer susceptibility. METHODS: We performed PWAS of breast, endometrial, ovarian, and prostate cancers and their subtypes in several large European-ancestry discovery consortia (effective sample size: 237,483 cases/317,006 controls) and tested the results for replication in an independent European-ancestry GWAS (31,969 cases/410,350 controls)...