Related papers: Adjustment for Inconsistency in Adaptive Phase 2/3…
The purpose of a phase I dose-finding clinical trial is to investigate the toxicity profiles of various doses for a new drug and identify the maximum tolerated dose. Over the past three decades, various dose-finding designs have been…
Many phase II clinical trials have used survival outcomes as the primary endpoints in recent decades. Suppose the radiotherapy is evaluated in a phase II trial using survival outcomes. In that case, the competing risk issue often arises…
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,…
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…
The authors propose robust adaptive strategies based on stochastic minimax optimization for a series of simulated treatments on a one-dimensional patient phantom. The plan applied during the first fractions should be able to handle…
We consider a formal statistical design that allows simultaneous enrollment of a main cohort and a backfill cohort of patients in a dose-finding trial. The goal is to accumulate more information at various doses to facilitate dose…
Purpose: We propose a general framework for quantifying predictive uncertainties of dose-related quantities and leveraging this information in a dose mimicking problem in the context of automated radiation therapy treatment planning.…
Adaptive therapy is a dynamic cancer treatment protocol that updates (or "adapts") treatment decisions in anticipation of evolving tumor dynamics. This broad term encompasses many possible dynamic treatment protocols of patient-specific…
Recent FDA guidance on adaptive clinical trial designs defines bias as "a systematic tendency for the estimate of treatment effect to deviate from its true value", and states that it is desirable to obtain and report estimates of treatment…
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…
In recent years, the interest in developing adaptive solutions for online testing has grown significantly in the industry. While the advances related to this relative new technology have been developed in multiple domains, it lacks in the…
Over time, clinical trials have increasingly incorporated complex design and analysis elements such as interim analyses, adaptations, multiple endpoints, and sophisticated multiplicity schemes for multiple endpoints and/or treatment arms…
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…
Opportunistic pharmacokinetic (PK) studies have sparse and imbalanced clinical measurement data, and the impact of sample time errors is an important concern when seeking accurate estimates of treatment response. We evaluated an approximate…
We explore phase transitions of plan modification, which mainly focus on the conformant planning problems. By analyzing features of plan modification in conformant planning problems, quantitative results are obtained. If the number of…
Formulating accurate and robust classification strategies is a key challenge of developing diagnostic and antibody tests. Methods that do not explicitly account for disease prevalence and uncertainty therein can lead to significant…
Purpose: During discussions at the Data Science Roundtable meeting in Japan, there were instances where the adoption of the BOIN design was declined, attributed to the extension of study duration and increased sample size in comparison to…
Multi-stage stochastic programming is a well-established framework for sequential decision making under uncertainty by seeking policies that are fully adapted to the uncertainty. Often such flexible policies are not desirable, and the…
Background: Phase I trials desire to identify the maximum tolerated dose (MTD) early and proceed quickly to an expansion cohort or phase II trial for efficacy. We propose an early completion method based on multiple dosages to accelerate…
Clinical trial design ensures that primary analysis outcomes have strong statistical properties. However, mainstream methodology for randomised study design does not establish a formal link between statistical and clinical significance.…