Related papers: Dose-finding design based on level set estimation …
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…
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…
In traditional dose-finding studies, dose-limiting toxicity (DLT) is determined within a fixed time observation window where DLT is often defined as a binary outcome. In the setting of oncology dose-finding trials, often patients in…
Dual agent dose-finding trials study the effect of a combination of more than one agent, where the objective is to find the Maximum Tolerated Dose Combination (MTC), the combination of doses of the two agents that is associated with a…
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)…
Delineating and planning with respect to regions suspected to contain microscopic tumor cells is an inherently uncertain task in radiotherapy. The recently proposed \textit{clinical target distribution} (CTD) is an alternative to the…
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…
Dose-finding trials are a key component of the drug development process and rely on a statistical design to help inform dosing decisions. Triallists wishing to choose a design require knowledge of operating characteristics of competing…
Purpose: Various dose calculation algorithms are available for radiation therapy for cancer patients. However, these algorithms are faced with the tradeoff between efficiency and accuracy. The fast algorithms are generally less accurate,…
A general framework is proposed for Bayesian model-based designs of Phase I cancer trials, in which a general criterion for coherence (Cheung, 2005) of a design is also developed. This framework can incorporate both "individual" and…
Surrogate endpoint (SE) for overall survival in cancer patients is essential to improving the efficiency of oncology drug development. In practice, we may discover a new patient level association with survival, based on one or more clinical…
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…
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…
Level set estimation (LSE) classifies whether an unknown function's value exceeds a specified threshold for given inputs, a fundamental problem in many real-world applications. In active learning settings with limited initial data, we aim…
We propose a two-stage design for a clinical trial with an early stopping rule for safety. We use different criteria to assess early stopping and efficacy. The early stopping rule is based on a criteria that can be determined more quickly…
In the era of targeted therapy, there has been increasing concern about the development of oncology drugs based on the "more is better" paradigm, developed decades ago for chemotherapy. Recently, the US Food and Drug Administration (FDA)…
We consider a formal statistical design that allows simultaneous enrollment of a main cohort and a backfill cohort of patients in a dose-finding trial. The goal is to accumulate more information at various doses to facilitate dose…
Oncology dose-finding trials are shifting from identifying the maximum tolerated dose (MTD) to determining the optimal biological dose (OBD), driven by the need for efficient methods that consider both toxicity and efficacy. This is…
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…
Consider an experiment, where a new drug is tested for the first time on human subjects - healthy volunteers. Such experiments are often performed as dose-escalation studies: a set of increasing doses is pre-selected, individuals are…