Related papers: Improving Maximum Tolerated Dose Selection in Mode…
The primary goal of dose allocation in phase I trials is to minimize patient exposure to subtherapeutic or excessively toxic doses, while accurately recommending a phase II dose that is as close as possible to the maximum tolerated dose…
Traditional dose selection for oncology registration trials typically employs a one- or two-step single maximum tolerated dose (MTD) approach. However, this approach may not be appropriate for molecularly targeted therapy that tends to have…
Oncology drug development starts with a dose escalation phase to find the maximal tolerable dose (MTD). Dose limiting toxicity (DLT) is the primary endpoint for dose escalation phase. Traditionally, model-based dose escalation trial designs…
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…
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…
In oncology phase I trials, model-assisted designs have been increasingly adopted because they enable adaptive yet operationally simple dose adjustment based on accumulating safety data, leading to a paradigm shift in dose-escalation…
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…
We consider a Bayesian framework based on "probability of decision" for dose-finding trial designs. The proposed PoD-BIN design evaluates the posterior predictive probabilities of up-and-down decisions. In PoD-BIN, multiple grades of…
The primary objective of phase I oncology studies is to establish the safety profile of a new treatment and determine the maximum tolerated dose (MTD). This is motivated by the development of cytotoxic agents based on the underlying…
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…
Broadening eligibility criteria in cancer trials has been advocated to represent the true patient population more accurately. While the advantages are clear in terms of generalizability and recruitment, novel dose-finding designs are needed…
Benchmark dose (BMD; a dose associated with a specified change in response) is used to determine the point of departure for the acceptable daily intake of substances for humans. Multiple dose-response relationship models are considered in…
Successful pharmaceutical drug development requires finding correct doses that provide an optimum balance between efficacy and toxicity. Competing responses to dose such as efficacy and toxicity often will increase with dose, and it is…
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 primary object of a phase I clinical trial is to determine the maximum tolerated dose (MTD). Typically, the MTD is identified using a dose-escalation study, where initial subjects are treated at the lowest dose level and subsequent…
Combination of several anti-cancer treatments has typically been presumed to have enhanced drug activity. Motivated by a real clinical trial, this paper considers phase I-II dose finding designs for dual-agent combinations, where one main…
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…
There is wide interest in studying how the distribution of a continuous response changes with a predictor. We are motivated by environmental applications in which the predictor is the dose of an exposure and the response is a health…
Model-informed precision dosing (MIPD) using therapeutic drug/biomarker monitoring offers the opportunity to significantly improve the efficacy and safety of drug therapies. Current strategies comprise model-informed dosing tables or are…
Dose-finding studies in oncology often include an up-and-down dose transition rule that assigns a dose to each cohort of patients based on accumulating data on dose-limiting toxicity (DLT) events. In making a dose transition decision, a key…