相关论文: Estimands for Early Phase Dose Optimization Trials…
Designing modern oncology trials requires synthesizing evidence from prior studies to inform hypothesis generation and sample size determination. Trial designs based on incomplete or imprecise summaries can lead to misspecified hypotheses…
Molecular optimization is a crucial aspect of drug discovery, aimed at refining molecular structures to enhance drug efficacy and minimize side effects, ultimately accelerating the overall drug development process. Many molecular…
We consider the optimal design problem for identifying effective dose combinations within drug combination studies where the effect of the combination of two drugs is investigated. Drug combination studies are becoming increasingly…
In this paper, a methodology is proposed that enables to analyze the sensitivity of the outcome of a therapy to unavoidable high dispersion of the patient specific parameters on one hand and to the choice of the parameters that define the…
The effectiveness of personalized oncology treatments ultimately depends on whether outcomes can be causally attributed to the treatment. Advances in precision oncology have improved molecular profiling of individuals, and tailored…
Geometric uncertainty can degrade treatment quality in radiation therapy. While margins and robust optimization mitigate these effects, they provide only implicit control over clinical goal fulfillment probability. We therefore develop a…
Interval designs are a class of phase I trial designs for which the decision of dose assignment is determined by comparing the observed toxicity rate at the current dose with a prespecified (toxicity tolerance) interval. If the observed…
Duration of response (DOR) and time to response (TTR) are typically evaluated as secondary endpoints in early-stage clinical studies in oncology when efficacy is assessed by the best overall response (BOR) and presented as the overall…
One of the challenges in the design of confirmatory trials is to deal with uncertainties regarding the optimal target population for a novel drug. Adaptive enrichment designs (AED) which allow for a data-driven selection of one or more…
In many phase II trials in solid tumours, patients are assessed using endpoints based on the Response Evaluation Criteria in Solid Tumours (RECIST) scale. Often, analyses are based on the response rate. This is the proportion of patients…
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,…
Objective: Spatiotemporal optimization in radiation therapy involves determining the optimal number of dose delivery fractions (temporal) and the optimal dose per fraction (spatial). Traditional approaches focus on maximizing the…
Dose-finding clinical trials in oncology aim to estimate the maximum tolerated dose (MTD), based on safety traditionally obtained from the clinician's perspective. While the collection of patient-reported outcomes (PROs) has been advocated…
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)…
Delineating and planning with respect to regions suspected to contain microscopic tumor cells is an inherently uncertain task in radiotherapy. The recently proposed \textit{clinical target distribution} (CTD) is an alternative to 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…
Nowadays, more and more clinical trials choose combinational agents as the intervention to achieve better therapeutic responses. However, dose-finding for combinational agents is much more complicated than single agent as the full order of…
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…
We identify three properties of the standard oncology phase I trial design or 3 + 3 design. We show that the standard design implicitly uses isotonic regression to estimate a maximum tolerated dose. We next illustrate the 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…