相关论文: Time-to-Event Model-Assisted Designs to Accelerate…

In oncology dose-finding trials, due to staggered enrollment, it might be desirable to make dose-assignment decisions in real-time in the presence of pending toxicity outcomes, for example, when the dose-limiting toxicity is late-onset.…

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),…

Mid-study design modifications are becoming increasingly accepted in confirmatory clinical trials, so long as appropriate methods are applied such that error rates are controlled. It is therefore unfortunate that the important case of…

Clinical trials are an integral component of medical research. Trials require careful design to, for example, maintain the safety of participants, use resources efficiently and allow clinically meaningful conclusions to be drawn. Adaptive…

Phase I dose-escalation trials must be guided by a safety model in order to avoid exposing patients to unacceptably high risk of toxicities. Traditionally, these trials are based on one type of schedule. In more recent practice, however,…

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…

Treatment of cancer has rapidly evolved over time in quite dramatic ways, for example from chemotherapies, targeted therapies to immunotherapies and chimeric antigen receptor T-cells. Nonetheless, the basic design of early phase I trials in…

Clinical trials with time-to-event endpoints, such as overall survival (OS) or progression-free survival (PFS), are fundamental for evaluating new treatments, particularly in immuno-oncology. However, modern therapies, such as…

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…

An objective of phase I dose-finding trials is to find the maximum tolerated dose; the dose with a particular risk of toxicity. Frequently, this risk is assessed across the first cycle of therapy. However, in oncology, a course of treatment…

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…

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…

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…

In developing products for rare diseases, statistical challenges arise due to the limited number of patients available for participation in drug trials and other clinical research. Bayesian adaptive clinical trial designs offer the…

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…

Time-to-event endpoints are central to evaluate treatment efficacy across many disease areas. Many trial protocols include interim analyses within group-sequential designs that control type I error via spending functions or boundary…

Adaptive designs are increasingly used in clinical trials and online experiments to improve participant outcomes by dynamically updating treatment allocation as data accumulate. In practice, experimenters often consider multiple candidate…

Adaptive enrichment allows for pre-defined patient subgroups of interest to be investigated throughout the course of a clinical trial. Many trials which measure a long-term time-to-event endpoint often also routinely collect repeated…

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…

Adaptive sample size re-estimation, early stopping, and trial re-design at interim analyses can reduce expected sample sizes in randomised trials. Cluster randomised trials, in which groups of participants are randomly allocated to…