Related papers: Time-to-Event Model-Assisted Designs to Accelerate…
Often in Phase 3 clinical trials measuring a long-term time-to-event endpoint, such as overall survival or progression-free survival, investigators also collect repeated measures on biomarkers which may be predictive of the primary…
Biomarker-guided designs are increasingly used to evaluate personalized treatments based on patients' biomarker status in Phase II and III clinical trials. With adaptive enrichment, these designs can improve the efficiency of evaluating the…
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…
Adaptive subgroup enrichment design is an efficient design framework that allows accelerated development for investigational treatments while also having flexibility in population selection within the course of the trial. The adaptive…
A new approach to adaptive design of clinical trials is proposed in a general multiparameter exponential family setting, based on generalized likelihood ratio statistics and optimal sequential testing theory. These designs are easy to…
For many years Phase I and Phase II clinical trials were conducted separately, but there was a recent shift to combine these Phases. While a variety of Phase~I/II model-based designs for cytotoxic agents were proposed in the literature,…
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…
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…
Safety evaluation is an essential component of clinical trials. To protect study participants, these studies often implement safety stopping rules that will halt the trial if an excessive number of toxicity events occur. Existing safety…
For biological experiments aiming at calibrating models with unknown parameters, a good experimental design is crucial, especially for those subject to various constraints, such as financial limitations, time consumption and physical…
It is a common practice in randomized clinical trials with the standard survival outcome to follow patients until a prespecified number of events have been observed, a type of trial known as the event-driven trial. The event-driven design…
This paper introduces a new Phase I design aimed at enhancing the performance of existing methods, including algorithm-based, model-based, and model-assisted designs. The design, developed by integrating the concept of Fisher information,…
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…
It is increasingly common for therapies in oncology to be given in combination. In some cases, patients can benefit from the interaction between two drugs, although often at the risk of higher toxicity. A large number of designs to conduct…
FDA's Project Optimus initiative for oncology drug development emphasizes selecting a dose that optimizes both efficacy and safety. When an inferentially adaptive Phase 2/3 design with dose selection is implemented to comply with the…
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…
Time-to-event outcomes are commonly used as primary endpoints in randomized clinical trials. Despite this, relatively little work incorporates baseline covariate information while also accounting for stratified randomization, a common form…
Purpose: The early identification of maximum tolerated dose (MTD) in phase I trial leads to faster progression to a phase II trial or an expansion cohort to confirm efficacy. Methods: We propose a novel adaptive design for identifying MTD…
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…
Immunotherapies have revolutionized cancer treatment. Unlike chemotherapies, immune agents often take longer time to show benefit, and the complex and unique mechanism of action of these agents renders the use of multiple endpoints more…