Related papers: ROSE: Randomized Optimal Selection Design for Dose…
An individualized dose rule recommends a dose level within a continuous safe dose range based on patient level information such as physical conditions, genetic factors and medication histories. Traditionally, personalized dose finding…
The Randomized Controlled Trial (RCT) or A/B testing is considered the gold standard method for estimating causal effects. Fisher famously advocated randomly allocating experiment units into treatment and control groups to preclude…
We propose to use Bayesian optimization (BO) to improve the efficiency of the design selection process in clinical trials. BO is a method to optimize expensive black-box functions, by using a regression as a surrogate to guide the search.…
The treatment assignment mechanism in a randomized clinical trial can be optimized for statistical efficiency within a specified class of randomization mechanisms. Optimal designs of this type have been characterized in terms of the…
Immunotherapies and targeted therapies have gained popularity due to their promising therapeutic effects across multiple treatment areas. The focus of early phase dose-finding clinical trials has shifted from finding the maximum tolerated…
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…
We consider robust optimal experimental design (ROED) for nonlinear Bayesian inverse problems governed by partial differential equations (PDEs). An optimal design is one that maximizes some utility quantifying the quality of the solution of…
In a sequential multiple-assignment randomized trial (SMART), a sequence of treatments is given to a patient over multiple stages. In each stage, randomization may be done to allocate patients to different treatment groups. Even though…
We propose Locally Optimal Restricted Designs (LORDs) for phase I/II dose-finding studies that focus on both efficacy and toxicity outcomes. As an illustrative application, we find various LORDs for a 4-parameter continuation-ratio (CR)…
Development and optimization of biopharmaceutical production processes with cell cultures is cost- and time-consuming and often performed rather empirically. Efficient optimization of multiple-objectives like process time, viable cell…
Allocating patients to treatment arms during a trial based on the observed responses accumulated prior to the decision point, and sequential adaptation of this allocation,, could minimize the expected number of failures or maximize total…
Nonlinear regression models addressing both efficacy and toxicity outcomes are increasingly used in dose-finding trials, such as in pharmaceutical drug development. However, research on related experimental design problems for corresponding…
Minimizing the number of patients exposed to potentially harmful drugs in early onco logical trials is a major concern during planning. Adaptive designs account for the inherent uncertainty about the true effect size by determining the…
Group sequential designs (GSDs) are well established and the most commonly used adaptive design in confirmatory clinical trials with interim analyses. However, they remain underutilised, and their implementation involves unique theoretical…
Recently, the strategy for dose optimization in oncology has shifted to conduct Phase 2 randomized controlled trials with multiple doses. Optimal biologic dose selection from Phase 1 trial data to determine candidate doses for Phase 2…
Effective disease treatment often requires precise control of the release of the active pharmaceutical ingredient (API). In this work, we present a computational inverse design approach to determine the optimal drug composition that yields…
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…
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…
The Finite Selection Model (FSM) was developed by Carl Morris in the 1970s for the design of the RAND Health Insurance Experiment (HIE) (Morris 1979, Newhouse et al. 1993), one of the largest and most comprehensive social science…
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…