Related papers: Two-dose vs. Three-Dose Optimization Under Sample …
A mathematical model for time development of metastases and their distribution in size and carrying capacity is presented. The model is used to theoretically investigate anti-cancer therapies such as surgery and chemical treatments…
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…
Phase I early-phase clinical studies aim at investigating the safety and the underlying dose-toxicity relationship of a drug or combination. While little may still be known about the compound's properties, it is crucial to consider…
Any process in which competing solutions replicate with errors and numbers of their copies depend on their respective fitnesses is the evolutionary optimization process. As during carcinogenesis mutated genomes replicate according to their…
A two-stage adaptive optimal design is an attractive option for increasing the efficiency of clinical trials. In these designs, based on interim data, the locally optimal dose is chosen for further exploration, which induces dependencies…
We use the exact finite sample likelihood and statistical decision theory to answer questions of ``why?'' and ``what should you have done?'' using data from randomized experiments and a utility function that prioritizes safety over…
Although there is an extensive statistical literature showing the disadvantages of discretizing continuous variables, categorization is a common practice in clinical research which results in substantial loss of information. A large…
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 aim of this paper is twofold. First, three theoretical principles are formalized: randomization, overrepresentation and restriction. We develop these principles and give a rationale for their use in choosing the sampling design in a…
Randomization is a common technique used in clinical trials to eliminate potential bias and confounders in a patient population. Equal allocation to treatment groups is the standard due to its optimal efficiency in many cases. However, in…
The initiation of dose optimization has driven a paradigm shift in oncology clinical trials to determine the optimal biological dose (OBD). Early-phase trials with randomized doses can facilitate additional investigation of the identified…
Background: Phase I trials desire to identify the maximum tolerated dose (MTD) early and proceed quickly to an expansion cohort or phase II trial for efficacy. We propose an early completion method based on multiple dosages to accelerate…
Phase II dose finding studies in clinical drug development are typically conducted to adequately characterize the dose response relationship of a new drug. An important decision is then on the choice of a suitable dose response function to…
We propose a new integrated phase I/II trial design to identify the most efficacious dose combination that also satisfies certain safety requirements for drug-combination trials. We first take a Bayesian copula-type model for dose finding…
We consider the problem of constructing probabilistic predictions that lead to accurate decisions when employed by downstream users to inform actions. For a single decision maker, designing an optimal predictor is equivalent to minimizing a…
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…
The treatment allocation mechanism in a randomized clinical trial can be optimized by maximizing the nonparametric efficiency bound for a specific measure of treatment effect. Optimal treatment allocations which may or may not depend on…
2-in-1 design (Chen et al. 2018) is becoming popular in oncology drug development, with the flexibility of using different endpoints at different decision time. Based on the observed interim data, sponsors choose either to seamlessly…
In previous articles, we formalized the problem of optimal allocation strategies for a (perfect) vaccine in an infinite-dimensional metapopulation model. The aim of the current paper is to illustrate this theoretical framework with multiple…
Two-phase outcome dependent sampling (ODS) is widely used in many fields, especially when certain covariates are expensive and/or difficult to measure. For two-phase ODS, the conditional maximum likelihood (CML) method is very attractive…