相关论文: A Comparative Evaluation of Bayesian Model-Assiste…

Immunotherapies and targeted therapies have gained popularity due to their promising therapeutic effects across multiple treatment areas. The focus of early phase dose-finding clinical trials has shifted from finding the maximum tolerated…

Traditional phase I dose finding cancer clinical trial designs aim to determine the maximum tolerated dose (MTD) of the investigational cytotoxic agent based on a single toxicity outcome, assuming a monotone dose-response relationship.…

We propose a Bayesian optimal phase 2 design for jointly monitoring efficacy and toxicity, referred to as BOP2-TE, to improve the operating characteristics of the BOP2 design proposed by Zhou et al. (2017). BOP2-TE utilizes a…

In this article, we propose a phase I-II design in two stages for the combination of molecularly targeted therapies. The design is motivated by a published case study that combines a MEK and a PIK3CA inhibitors; a setting in which higher…

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…

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 conventional phase II trial design paradigm is to make the go/no-go decision based on the hypothesis testing framework. Statistical significance itself alone, however, may not be sufficient to establish that the drug is clinically…

In phase I dose escalation studies for dual-agent combinations, at least one drug often has an established monotherapy dose. Consequently, substantial prior clinical safety data often exist for one or more monotherapies, allowing the study…

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…

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…

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…

Phase I-II cancer clinical trial designs are intended to accelerate drug development. In cases where efficacy cannot be ascertained in a short period of time, it is common to divide the study in two stages: i) a first stage in which dose is…

Early phase, personalized dose-finding trials for combination therapies seek to identify patient-specific optimal biological dose (OBD) combinations, which are defined as safe dose combinations which maximize therapeutic benefit for a…

In Phase I/II dose-finding trials, the objective is to find the Optimal Biological Dose (OBD), a dose that is both safe and efficacious that maximises some optimality criterion based on safety and efficacy. This is further complicated when…

In this paper we consider two-stage adaptive dose-response study designs, where the study design is changed at an interim analysis based on the information collected so far. In a simulation study, two approaches will be compared for these…

Immunotherapy has transformed cancer treatment, yet its delayed therapeutic effects often lead to non-proportional hazards, rendering many conventional phase II designs underpowered and prone to type I error inflation. To address this…

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…

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…

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…