Related papers: The i3+3 Design for Phase I Clinical Trials
We propose a rule-based statistical design for combination dose-finding trials with two agents. The Ci3+3 design is an extension of the i3+3 design with simple decision rules comparing the observed toxicity rates and equivalence intervals…
Background -- In phase I clinical trials, historical data may be available through multi-regional programs, reformulation of the same drug, or previous trials for a drug under the same class. Statistical designs that borrow information from…
The landscape of dose-finding designs for phase I clinical trials is rapidly shifting in the recent years, noticeably marked by the emergence of interval-based designs. We categorize them as the iDesigns and the IB-Designs. The iDesigns are…
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…
Purpose: During discussions at the Data Science Roundtable meeting in Japan, there were instances where the adoption of the BOIN design was declined, attributed to the extension of study duration and increased sample size in comparison to…
We consider a modified Ci3+3 (MCi3+3) design for dual-agent dose-finding trials in which both agents are tested on multiple doses. This usually happens when the agents are novel therapies. The MCi3+3 design offers a two-stage or three-stage…
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 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…
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…
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,…
If explicit, formal consideration of clinical pharmacology at all informs the design and conduct of modern oncology dose-finding trials, the designs themselves hardly attest to this. Yet in conducting a trial, investigators affirm that they…
We identify three properties of the standard oncology phase I trial design or 3 + 3 design. We show that the standard design implicitly uses isotonic regression to estimate a maximum tolerated dose. We next illustrate the relationship…
Two useful strategies to speed up drug development are to increase the patient accrual rate and use novel adaptive designs. Unfortunately, these two strategies often conflict when the evaluation of the outcome cannot keep pace with the…
Adaptive designs have been proposed for clinical trials in which the nuisance parameters or alternative of interest are unknown or likely to be misspecified before the trial. Whereas most previous works on adaptive designs and mid-course…
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…
Adaptive designs for clinical trials permit alterations to a study in response to accumulating data in order to make trials more flexible, ethical and efficient. These benefits are achieved while preserving the integrity and validity of the…
The traditional more-is-better dose selection paradigm, developed based on cytotoxic chemotherapeutics, is often problematic When applied to the development of novel molecularly targeted agents (e.g., kinase inhibitors, monoclonal…
Novel dose-finding designs, using estimation to assign the best estimated maximum- tolerated-dose (MTD) at each point in the experiment, most commonly via Bayesian techniques, have recently entered large-scale implementation in Phase I…
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…
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…