相关论文: Hi3+3: A Model-Assisted Dose-Finding Design Borrow…

Purpose: The 3+3 design has been shown to be less likely to achieve the objectives of phase I dose-finding trials when compared with more advanced model-based designs. One major criticism of the 3+3 design is that it is based on simple…

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…

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…

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…

Use of historical data and real-world evidence holds great potential to improve the efficiency of clinical trials. One major challenge is how to effectively borrow information from historical data while maintaining a reasonable type I…

Incorporating historical data or real-world evidence has a great potential to improve the efficiency of phase I clinical trials and to accelerate drug development. For model-based designs, such as the continuous reassessment method (CRM),…

In early phase drug development of combination therapy, the primary objective is to preliminarily assess whether there is additive activity from a novel agent when combined with an established monotherapy. Due to potential feasibility…

Information borrowing from historical data is gaining attention in clinical trials of rare and pediatric diseases, where statistical power may be insufficient for confirmation of efficacy if the sample size is small. Although Bayesian…

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…

There is currently a focus on statistical methods which can use historical trial information to help accelerate the discovery, development and delivery of medicine. Bayesian methods can be constructed so that the borrowing is "dynamic" in…

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…

Clinical trials in the medical domain are constrained by budgets. The number of patients that can be recruited is therefore limited. When a patient population is heterogeneous, this creates difficulties in learning subgroup specific…

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…

In current clinical trial development, historical information is receiving more attention as it provides utility beyond sample size calculation. Meta-analytic-predictive (MAP) priors and robust MAP priors have been proposed for…

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…

Dose-escalation trials in oncology drug development still today typically aim to identify 1-size-fits-all dose recommendations, as arbitrary quantiles of the toxicity thresholds evident in patient samples. In the late 1990s efforts to…

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…

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 enrichment trials aim to identify and recruit participants most likely to benefit from treatment based on evolving biomarker evidence, with the goal of informing individualized treatment recommendations. Bayesian methods are well…

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…