相关论文: Estimands for Early Phase Dose Optimization Trials…

Conventionally, a first-in-human phase I trial in healthy volunteers aims to confirm the safety of a drug in humans. In such situations, volunteers should not suffer from any safety issues and simple algorithm-based dose-escalation schemes…

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…

Dose-finding clinical trials in oncology aim to determine the maximum tolerated dose (MTD) of a new drug, generally defined by the proportion of patients with short-term dose-limiting toxicities (DLTs). Model-based approaches for such phase…

In early-phase cancer clinical trials, the limited availability of data presents significant challenges in developing a framework to efficiently quantify treatment effectiveness. To address this, we propose a novel utility-based Bayesian…

The commonplace description of phase 1 clinical trials in oncology as "primarily concerned with safety" is belied by their near universal adoption of dose-escalation practices which are inherently unsafe. In contrast with dose titration,…

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…

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…

Optimizing doses for multiple indications is challenging. The pooled approach of finding a single optimal biological dose (OBD) for all indications ignores that dose-response or dose-toxicity curves may differ between indications, resulting…

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…

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…

The use of drug combinations in clinical trials is increasingly common during the last years since a more favorable therapeutic response may be obtained by combining drugs. In phase I clinical trials, most of the existing methodology…

We propose a new integrated phase I/II trial design to identify the most efficacious dose combination that also satisfies certain safety requirements for drug-combination trials. We first take a Bayesian copula-type model for dose finding…

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…

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…

Model-assisted designs have garnered significant attention in recent years due to their high accuracy in identifying the maximum tolerated dose (MTD) and their operational simplicity. To identify the MTD, they employ estimated dose limiting…

Time-to-event estimands are central to many oncology clinical trials. The estimand framework (addendum to the ICH E9 guideline) calls for precisely defining the treatment effect of interest to align with the clinical question of interest…

Dose-finding trials for oncology studies are traditionally designed to assess safety in the early stages of drug development. With the rise of molecularly targeted therapies and immuno-oncology compounds, biomarker-driven approaches have…

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…

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…

Adaptive Phase 2/3 designs hold great promise in contemporary oncology drug development, especially when limited data from Phase 1 dose-finding is insufficient for identifying an optimal dose. However, there is a general concern about…