相关论文: Precision Dose-finding Cancer Clinical Trials in t…

With the development of novel therapies such as molecularly targeted agents and immunotherapy, the maximum tolerated dose paradigm that "more is better" does not necessarily hold anymore. In this context, doses and schedules of novel…

An important objective in the development of targeted therapies is to identify the populations where the treatment under consideration has positive benefit risk balance. We consider pivotal clinical trials, where the efficacy of a treatment…

The keyboard design is a novel phase I dose-finding method that is simple and has good operating characteristics. This paper studies theoretical properties of the keyboard design, including the optimality of its decision rules, coherence in…

Cancer has become one of the most widespread diseases in the world. Specifically, breast cancer is diagnosed more often than any other type of cancer. However, breast cancer patients and their individual tumors are often unique. Identifying…

In the era of targeted therapy, there has been increasing concern about the development of oncology drugs based on the "more is better" paradigm, developed decades ago for chemotherapy. Recently, the US Food and Drug Administration (FDA)…

Adaptive Phase 2/3 designs hold great promise in contemporary oncology drug development, especially when limited data from Phase 1 dose-finding is insufficient for identifying an optimal dose. However, there is a general concern about…

Cancer is a complex genetic disease involving uncontrolled cell growth and proliferation, and necessitates effective targeting of dysregulated cellular pathways underlying cancer progression. Multiple genetic and epigenetic alterations…

Large variability between cell lines brings a difficult optimization problem of drug selection for cancer therapy. Standard approaches use prediction of value for this purpose, corresponding e.g. to expected value of their distribution.…

The primary objective of phase I oncology studies is to establish the safety profile of a new treatment and determine the maximum tolerated dose (MTD). This is motivated by the development of cytotoxic agents based on the underlying…

Precision medicine is an approach for disease treatment that defines treatment strategies based on the individual characteristics of the patients. Motivated by an open problem in cancer genomics, we develop a novel model that flexibly…

The concept of personalised medicine in cancer therapy is becoming increasingly important. There already exist drugs administered specifically for patients with tumours presenting well-defined mutations. However, the field is still in its…

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…

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…

With the advancement of high-throughput biotechnologies, we increasingly accumulate biomedical data about diseases, especially cancer. There is a need for computational models and methods to sift through, integrate, and extract new…

The US FDA's Project Optimus initiative that emphasizes dose optimization prior to marketing approval represents a pivotal shift in oncology drug development. It has a ripple effect for rethinking what changes may be made to conventional…

Phase I dose-finding trials in oncology seek to find the maximum tolerated dose (MTD) of a drug under a specific schedule. Evaluating drug-schedules aims at improving treatment safety while maintaining efficacy. However, while we can…

Recently there has been much work on early phase cancer designs that incorporate both toxicity and efficacy data, called Phase I-II designs because they combine elements of both phases. However, they do not explicitly address the Phase II…

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…

In cancer research, high-throughput profiling has been extensively conducted. In recent studies, the integrative analysis of data on multiple cancer patient groups/subgroups has been conducted. Such analysis has the potential to reveal the…

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…