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We propose a two-stage design for a clinical trial with an early stopping rule for safety. We use different criteria to assess early stopping and efficacy. The early stopping rule is based on a criteria that can be determined more quickly…

Methodology · Statistics 2013-07-25 Daniel Zelterman

In oncology, phase II studies are crucial for clinical development plans as such studies identify potent agents with sufficient activity to continue development in the subsequent phase III trials. Traditionally, phase II studies are…

Methodology · Statistics 2023-08-08 Takuya Yoshimoto , Satoru Shinoda , Kouji Yamamoto , Kouji Tahata

Traditionally, the major objective in phase I trials is to identify a working-dose for subsequent studies, whereas the major endpoint in phase II and III trials is treatment efficacy. The dose sought is typically referred to as the maximum…

Methodology · Statistics 2016-08-14 Mourad Tighiouart , André Rogatko

Dose-finding studies are frequently conducted to evaluate the effect of different doses or concentration levels of a compound on a response of interest. Applications include the investigation of a new medicinal drug, a herbicide or…

Applications · Statistics 2011-08-01 Björn Bornkamp , Frank Bretz , Holger Dette , José Pinheiro

A common problem in Phase II clinical trials is the comparison of dose response curves corresponding to different treatment groups. If the effect of the dose level is described by parametric regression models and the treatments differ in…

Statistics Theory · Mathematics 2016-03-16 Chrystel Feller , Kirsten Schorning , Holger Dette , Georgina Bermann , Björn Bornkamp

It is possible to find the optimized radiation dose per session for a radiotherapy (RT) treatment, using a population dynamics model. This has already been done in a previous work for a protocol with 30 sessions and a fixed dose per…

Pathologic complete response (pCR) is a common primary endpoint for a phase II trial or even accelerated approval of neoadjuvant cancer therapy. If granted, a two-arm confirmatory trial is often required to demonstrate the efficacy with a…

Methodology · Statistics 2021-05-25 Marta Bofill Roig , Yu Shen , Guadalupe Gómez Melis

For many years Phase I and Phase II clinical trials were conducted separately, but there was a recent shift to combine these Phases. While a variety of Phase~I/II model-based designs for cytotoxic agents were proposed in the literature,…

Methodology · Statistics 2018-06-19 Pavel Mozgunov , Thomas Jaki

Prior probabilities of clinical hypotheses are not systematically used for clinical trial design yet, due to a concern that poor priors may lead to poor decisions. To address this concern, a conservative approach to Bayesian trial design is…

Methodology · Statistics 2023-09-21 Fabio Rigat

In decommissioning projects of nuclear facilities, the radiological characterisation step aims to estimate the quantity and spatial distribution of different radionuclides. To carry out the estimation, measurements are performed on site to…

Methodology · Statistics 2023-05-15 Martin Wieskotten , Marielle Crozet , Bertrand Iooss , Céline Lacaux , Amandine Marrel

Identifying subgroups, which respond differently to a treatment, both in terms of efficacy and safety, is an important part of drug development. A well-known challenge in exploratory subgroup analyses is the small sample size in the…

Computation · Statistics 2016-06-28 Marius Thomas , Björn Bornkamp

In many clinical trials, individuals in different subgroups have experience differential treatment effects. This leads to individualized differences in treatment benefit. In this article, we introduce the general concept of predictive…

Methodology · Statistics 2018-07-11 Debashis Ghosh , Youngjoo Cho

In the last year more than 70,000 people have been brought to the UK hospitals with serious injuries. Each time a clinician has to urgently take a patient through a screening procedure to make a reliable decision on the trauma treatment.…

Artificial Intelligence · Computer Science 2008-05-27 L. Jakaite , V. Schetinin

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,…

Methodology · Statistics 2020-04-28 David C. Norris

Basket trials in oncology enroll multiple patients with cancer harboring identical gene alterations and evaluate their response to targeted therapies across cancer types. Several existing methods have extended a Bayesian hierarchical model…

Methodology · Statistics 2024-12-17 Ryo Kitabayashi , Hiroyuki Sato , Akihiro Hirakawa

We consider a Bayesian persuasion or information design problem where the sender tries to persuade the receiver to take a particular action via a sequence of signals. This we model by considering multi-phase trials with different…

Theoretical Economics · Economics 2021-11-24 Shih-Tang Su , Vijay G. Subramanian , Grant Schoenebeck

Dose-response models express the effect of different dose or exposure levels on a specific outcome. In meta-analysis, where aggregated-level data is available, dose-response evidence is synthesized using either one-stage or two-stage models…

In cancer treatment, chemotherapy is administered according a constant schedule. The chronotherapy approach, considering chronobiological drug delivery, adapts the chemotherapy profile to the circadian rhythms of the human organism. This…

Quantitative Methods · Quantitative Biology 2016-04-12 Benjamin Schott , Johannes Stegmaier , Alexandre Arbaud , Markus Reischl , Ralf Mikut , Francis Lévi

The field of precision medicine aims to tailor treatment based on patient-specific factors in a reproducible way. To this end, estimating an optimal individualized treatment regime (ITR) that recommends treatment decisions based on patient…

Interfractional geometric uncertainties can lead to deviations of the actual delivered dose from the prescribed dose distribution. To better handle these uncertainties during treatment, the authors propose a dynamic framework for robust…

Medical Physics · Physics 2019-05-16 Michelle Böck , Kjell Eriksson , Anders Forsgren