Related papers: A Utility Score Framework for Dose Optimization St…
Dose optimization in oncology clinical trials has shifted from seeking the maximum tolerated dose to identifying the Optimal Biological Dose (OBD) that balances therapeutic benefits and risks across multiple clinical attributes. Existing…
Project Optimus, an initiative by the FDA's Oncology Center of Excellence, seeks to reform the dose-optimization and dose-selection paradigm in oncology. We propose a dose-optimization design that considers plateau efficacy profiles,…
The main objective of dose finding trials is to find an optimal dose amongst a candidate set for further research. The trial design in oncology proceeds in stages with a decision as to how to treat the next group of patients made at every…
The US FDA's Project Optimus initiative that emphasizes dose optimization prior to marketing approval represents a pivotal shift in oncology drug development. It has a ripple effect for rethinking what changes may be made to conventional…
The initiation of dose optimization has driven a paradigm shift in oncology clinical trials to determine the optimal biological dose (OBD). Early-phase trials with randomized doses can facilitate additional investigation of the identified…
The conventional more-is-better dose selection paradigm, which targets the maximum tolerated dose (MTD), is not suitable for the development of targeted therapies and immunotherapies as the efficacy of these novel therapies may not increase…
The US Food and Drug Administration launched Project Optimus with the aim of shifting the paradigm of dose-finding and selection towards identifying the optimal biological dose that offers the best balance between benefit and risk, rather…
An important objective in the development of targeted therapies is to identify the populations where the treatment under consideration has positive benefit risk balance. We consider pivotal clinical trials, where the efficacy of a treatment…
Phase I dose escalation trials in oncology generally aim to find the maximum tolerated dose (MTD). However, with the advent of molecular targeted therapies and antibody drug conjugates, dose limiting toxicities are less frequently observed,…
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…
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…
The U.S. Food and Drug Administration (FDA) launched Project Optimus to shift the objective of dose selection from the maximum tolerated dose to the optimal biological dose (OBD), optimizing the benefit-risk tradeoff. One approach…
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…
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 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…
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,…
Dose optimization is a hallmark of Project Optimus for oncology drug development. The number of doses to include in a dose optimization study depends on the totality of evidence, which is often unclear in early-phase development. With equal…
Identification of optimal dose combinations in early phase dose-finding trials is challenging, due to the trade-off between precisely estimating the many parameters required to flexibly model the possibly non-monotonic dose-response…
This article presents a pragmatic framework for making formal, utility-based decisions from statistical inferences. The method calculates an expected utility score for an intervention by combining Bayesian posterior probabilities of…
The Project Optimus initiative by the FDA's Oncology Center of Excellence is widely viewed as a groundbreaking effort to change the $\textit{status quo}$ of conventional dose-finding strategies in oncology. Unlike in other therapeutic areas…