相关论文: Statistical Frameworks for Oncology Dose-Finding D…

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…

Clinical trials are essential to drug development but time-consuming, costly, and prone to failure. Accurate trial outcome prediction based on historical trial data promises better trial investment decisions and more trial success. Existing…

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…

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,…

Precision oncology, the genetic sequencing of tumors to identify druggable targets, has emerged as the standard of care in the treatment of many cancers. Nonetheless, due to the pace of therapy development and variability in patient…

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…

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…

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…

We propose Locally Optimal Restricted Designs (LORDs) for phase I/II dose-finding studies that focus on both efficacy and toxicity outcomes. As an illustrative application, we find various LORDs for a 4-parameter continuation-ratio (CR)…

In safety-critical decision-making scenarios being able to identify worst-case outcomes, or dead-ends is crucial in order to develop safe and reliable policies in practice. These situations are typically rife with uncertainty due to unknown…

Oncology drug development starts with a dose escalation phase to find the maximal tolerable dose (MTD). Dose limiting toxicity (DLT) is the primary endpoint for dose escalation phase. Traditionally, model-based dose escalation trial designs…

A general framework is proposed for Bayesian model-based designs of Phase I cancer trials, in which a general criterion for coherence (Cheung, 2005) of a design is also developed. This framework can incorporate both "individual" and…

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…

Online Controlled Experiments (OCEs) are the gold standard in evaluating the effectiveness of changes to websites. An important type of OCE evaluates different personalization strategies, which present challenges in low test power and lack…

Big data solutions are designed to cope with data of huge Volume and wide Variety, that need to be ingested at high Velocity and have potential Veracity issues, challenging characteristics that are usually referred to as the "4Vs of Big…

Subclassification and matching are often used in empirical studies to adjust for observed covariates; however, they are largely restricted to relatively simple study designs with a binary treatment and less developed for designs with a…

In personalised decision making, evidence is required to determine whether an action (treatment) is suitable for an individual. Such evidence can be obtained by modelling treatment effect heterogeneity in subgroups. The existing…

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…

Understanding the association between mixtures of environmental toxicants and time-to-pregnancy (TTP) is an important scientific question as sufficient evidence has emerged about the impact of individual toxicants on reproductive health and…

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…