Related papers: Optimal designs for active controlled dose finding…
We consider the optimal design problem for identifying effective dose combinations within drug combination studies where the effect of the combination of two drugs is investigated. Drug combination studies are becoming increasingly…
In a recent paper Dette et al. (2014) introduced optimal design problems for dose fnding studies with an active control. These authors concentrated on regression models with normal distributed errors (with known variance) and the problem of…
We consider design issues for toxicology studies when we have a continuous response and the true mean response is only known to be a member of a class of nested models. This class of non-linear models was proposed by toxicologists who were…
An important tool to evaluate the performance of any design is an optimal benchmark proposed by O'Quigley and others (2002, Biostatistics 3(1), 51-56) that provides an upper bound on the performance of a design under a given scenario. The…
The issue of determining not only an adequate dose but also a dosing frequency of a drug arises frequently in Phase II clinical trials. This results in the comparison of models which have some parameters in common. Planning such studies…
Phase 1-2 designs provide a methodological advance over phase 1 designs for dose finding by using both clinical response and toxicity. A phase 1-2 trial still may fail to select a truly optimal dose. because early response is not a perfect…
We construct optimal designs for estimating fetal malformation rate, prenatal death rate and an overall toxicity index in a toxicology study under a broad range of model assumptions. We use Weibull distributions to model these rates and…
In Phase I/II dose-finding trials, the objective is to find the Optimal Biological Dose (OBD), a dose that is both safe and efficacious that maximises some optimality criterion based on safety and efficacy. This is further complicated when…
The US Food and Drug Administration launched Project Optimus with the aim of shifting the paradigm of dose-finding and selection towards identifying the optimal biological dose that offers the best balance between benefit and risk, rather…
The purpose of a phase I dose-finding clinical trial is to investigate the toxicity profiles of various doses for a new drug and identify the maximum tolerated dose. Over the past three decades, various dose-finding designs have been…
Dose-finding trials are a key component of the drug development process and rely on a statistical design to help inform dosing decisions. Triallists wishing to choose a design require knowledge of operating characteristics of competing…
A common problem in Phase II clinical trials is the comparison of dose response curves corresponding to different treatment groups. If the effect of the dose level is described by parametric regression models and the treatments differ in…
In the development of new cancer treatment, an essential step is to determine the maximum tolerated dose (MTD) via phase I clinical trials. Generally speaking, phase I trial designs can be classified as either model-based or algorithm-based…
We consider the problem of constructing optimal designs for population pharmacokinetics which use random effect models. It is common practice in the design of experiments in such studies to assume uncorrelated errors for each subject. In…
We propose a Bayesian optimal phase 2 design for jointly monitoring efficacy and toxicity, referred to as BOP2-TE, to improve the operating characteristics of the BOP2 design proposed by Zhou et al. (2017). BOP2-TE utilizes a…
In this article, we propose a phase I-II design in two stages for the combination of molecularly targeted therapies. The design is motivated by a published case study that combines a MEK and a PIK3CA inhibitors; a setting in which higher…
Many chemical and biological experiments involve multiple treatment factors and often it is convenient to fit a nonlinear model in these factors. This nonlinear model can be mechanistic, empirical or a hybrid of the two. Motivated by…
The keyboard design is a novel phase I dose-finding method that is simple and has good operating characteristics. This paper studies theoretical properties of the keyboard design, including the optimality of its decision rules, coherence in…
Project Optimus, an initiative by the FDA's Oncology Center of Excellence, seeks to reform the dose-optimization and dose-selection paradigm in oncology. We propose a dose-optimization design that considers plateau efficacy profiles,…
We propose a computational approach to constructing exact designs on finite design spaces that are optimal for multiresponse regression experiments under a combination of the standard linear and specific 'sparsity' constraints. The linear…