Related papers: Optimal Approximate Designs for Comparison with Co…
In phase I dose escalation studies for dual-agent combinations, at least one drug often has an established monotherapy dose. Consequently, substantial prior clinical safety data often exist for one or more monotherapies, allowing the study…
In this paper, we study the design and analysis of experiments conducted on a set of units over multiple time periods where the starting time of the treatment may vary by unit. The design problem involves selecting an initial treatment time…
Adaptive experimental designs have gained popularity in clinical trials and online experiments. Unlike traditional, fixed experimental designs, adaptive designs can dynamically adjust treatment randomization probabilities and other design…
Hierarchical random effect models are used for different purposes in clinical research and other areas. In general, the main focus is on population parameters related to the expected treatment effects or group differences among all units of…
The primary objective of phase I cancer clinical trials is to evaluate the safety of a new experimental treatment and to find the maximum tolerated dose (MTD). We show that the MTD estimation problem can be regarded as a level set…
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…
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…
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…
This article discusses $A$-, $D$- and $E$-optimality results for multivariate crossover designs, where more than one response is measured from every period for each subject. The motivation for these multivariate designs comes from a $3…
In medical treatment and elsewhere, it has become standard to base treatment intensity (dosage) on evidence in randomized trials. Yet it has been rare to study how outcomes vary with dosage. In trials to obtain drug approval, the norm has…
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…
Dose optimization is a hallmark of Project Optimus for oncology drug development. The number of doses to include in a dose optimization study depends on the totality of evidence, which is often unclear in early-phase development. With equal…
The U.S. Food and Drug Administration (FDA) launched Project Optimus to shift the objective of dose selection from the maximum tolerated dose to the optimal biological dose (OBD), optimizing the benefit-risk tradeoff. One approach…
In this paper, the tools provided by the theory of Optimal Experimental Design are applied to a nonlinear calibration model. This is motivated by the need of estimating radiation doses using radiochromic films for radiotherapy purposes. The…
We consider repeated measurement designs when a residual or carry-over effect may be present in at most one later period. Since assuming an additive model may be unrealistic for some applications and leads to biased estimation of treatment…
The conventional more-is-better dose selection paradigm, which targets the maximum tolerated dose (MTD), is not suitable for the development of targeted therapies and immunotherapies as the efficacy of these novel therapies may not increase…
Phase I dose-finding trials are increasingly challenging as the relationship between efficacy and toxicity of new compounds (or combination of them) becomes more complex. Despite this, most commonly used methods in practice focus on…
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…
Aims: Combinations of treatments can offer additional benefit over the treatments individually. However, trials of these combinations are lower priority than the development of novel therapies, which can restrict funding, timelines and…
Nowadays, more and more clinical trials choose combinational agents as the intervention to achieve better therapeutic responses. However, dose-finding for combinational agents is much more complicated than single agent as the full order of…