Related papers: Bayesian Model Averaging for Partial Ordering Cont…
Recent years have seen increased interest in combining drug agents and/or schedules. Several methods for Phase I combination-escalation trials are proposed, among which, the partial ordering continual reassessment method (POCRM) gained…
The study of combinations of drugs/drug-schedules gained increasing attention in various therapeutic areas recently. In oncology, the aim of phase I combination clinical trial is to find the maximum tolerated combination (MTC). Many…
This paper proposes a novel criterion for the allocation of patients in Phase~I dose-escalation clinical trials aiming to find the maximum tolerated dose (MTD). Conventionally, using a model-based approach the next patient is allocated to…
In Oncology, trials evaluating drug combinations are becoming more common. While combination therapies bring the potential for greater efficacy, they also create unique challenges for ensuring drug safety. In Phase-I dose escalation trials…
Successful pharmaceutical drug development requires finding correct doses that provide an optimum balance between efficacy and toxicity. Competing responses to dose such as efficacy and toxicity often will increase with dose, and it is…
During the last twenty years there have been considerable methodological developments in the design and analysis of Phase 1, Phase 2 and Phase 1/2 dose-finding studies. Many of these developments are related to the continual reassessment…
An accurately identified maximum tolerated dose (MTD) serves as the cornerstone of successful subsequent phases in oncology drug development. Bayesian logistic regression model (BLRM) is a popular and versatile model-based dose-finding…
For many cancer sites low-dose risks are not known and must be extrapolated from those observed in groups exposed at much higher levels of dose. Measurement error can substantially alter the dose-response shape and hence the extrapolated…
This work introduces the Burdened Bayesian Logistic Regression Model (BBLRM), an enhancement of the Bayesian Logistic Regression Model (BLRM) for dose-finding in phase I oncology trials. The BLRM determines the maximum tolerated dose (MTD)…
Drug combination trials are increasingly common nowadays in clinical research. However, very few methods have been developed to consider toxicity attributions in the dose escalation process. We are motivated by a trial in which the…
The partially observable constrained optimization problems (POCOPs) impede data-driven optimization techniques since an infeasible solution of POCOPs can provide little information about the objective as well as the constraints. We endeavor…
Almost 30% of prostate cancer (PCa) patients undergoing radical prostatectomy (RP) experience biochemical recurrence (BCR), characterized by increased prostate specific antigen (PSA) and associated with increased mortality. Accurate early…
Most conventional risk analysis methods rely on a single best estimate of exposure per person which does not allow for adjustment for exposure-related uncertainty. Here, we propose a Bayesian model averaging method to properly quantify the…
Dose-finding trials for oncology studies are traditionally designed to assess safety in the early stages of drug development. With the rise of molecularly targeted therapies and immuno-oncology compounds, biomarker-driven approaches have…
The primary object of a phase I clinical trial is to determine the maximum tolerated dose (MTD). Typically, the MTD is identified using a dose-escalation study, where initial subjects are treated at the lowest dose level and subsequent…
We develop a nonparametric Bayesian modeling framework for clustered ordinal responses in developmental toxicity studies, which typically exhibit extensive heterogeneity. The primary focus of these studies is to examine the dose-response…
An important objective in biomedical risk assessment is estimation of minimum exposure levels that induce a pre-specified adverse response in a target population. The exposure/dose points in such settings are known as Benchmark Doses…
Background: The proportional odds (PO) model is the most common analytic method for ordinal outcomes in randomised controlled trials. While parameter estimates obtained under departures from PO can be interpreted as an average odds ratio,…
Autonomous Experimentation Platforms (AEPs) are advanced manufacturing platforms that, under intelligent control, can sequentially search the material design space (MDS) and identify parameters with the desired properties. At the heart of…
Mixed Models for Repeated Measures (MMRMs) are ubiquitous when analyzing outcomes of clinical trials. However, the linearity of the fixed-effect structure in these models largely restrict their use to estimating treatment effects that are…