Related papers: Statistical and Practical Considerations in Planni…
With the development of novel therapies such as molecularly targeted agents and immunotherapy, the maximum tolerated dose paradigm that "more is better" does not necessarily hold anymore. In this context, doses and schedules of novel…
Optimal design of a Phase I cancer trial can be formulated as a stochastic optimization problem. By making use of recent advances in approximate dynamic programming to tackle the problem, we develop an approximation of the Bayesian optimal…
We consider a dose-optimization design for first-in-human oncology trial that aims to identify a suitable dose for late-phase drug development. The proposed approach, called the Pharmacometrics-Enabled DOse OPtimization (PEDOOP) design,…
An early phase clinical trial is the first step in evaluating the effects in humans of a potential new anti-disease agent or combination of agents. Usually called "phase I" or "phase I/II" trials, these experiments typically have the…
The use of drug combinations in clinical trials is increasingly common during the last years since a more favorable therapeutic response may be obtained by combining drugs. In phase I clinical trials, most of the existing methodology…
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…
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…
One common approach for dose optimization is a two-stage design, which initially conducts dose escalation to identify the maximum tolerated dose (MTD), followed by a randomization stage where patients are assigned to two or more doses to…
The primary goal of a two-stage Phase I/II trial is to identify the optimal dose for the following large-scale Phase III trial. Recently, Phase I dose-finding designs have shifted from identifying the maximum tolerated dose (MTD) to the…
A central goal in designing clinical trials is to find the test that maximizes power (or equivalently minimizes required sample size) for finding a false null hypothesis subject to the constraint of type I error. When there is more than one…
Clinical trials are pivotal in the drug discovery process to determine the safety and efficacy of a drug candidate. The high failure rates of these trials are attributed to deficiencies in clinical model development and protocol design.…
An objective of phase I dose-finding trials is to find the maximum tolerated dose; the dose with a particular risk of toxicity. Frequently, this risk is assessed across the first cycle of therapy. However, in oncology, a course of treatment…
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…
Early phase, personalized dose-finding trials for combination therapies seek to identify patient-specific optimal biological dose (OBD) combinations, which are defined as safe dose combinations which maximize therapeutic benefit for a…
Interval designs are a class of phase I trial designs for which the decision of dose assignment is determined by comparing the observed toxicity rate at the current dose with a prespecified (toxicity tolerance) interval. If the observed…
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…
Phase I clinical trials are designed to test the safety (non-toxicity) of drugs and find the maximum tolerated dose (MTD). This task becomes significantly more challenging when multiple-drug dose-combinations (DC) are involved, due to the…
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…
With increasing interest in adaptive clinical trial designs, challenges are present to drug supply chain management which may offset the benefit of adaptive designs. Thus, it is necessary to develop an optimization tool to facilitate the…
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…