Related papers: A Unified Decision Framework for Phase I Dose-Find…
Phase II dose finding studies in clinical drug development are typically conducted to adequately characterize the dose response relationship of a new drug. An important decision is then on the choice of a suitable dose response function to…
An important task in drug development is to identify patients, which respond better or worse to an experimental treatment. Identifying predictive covariates, which influence the treatment effect and can be used to define subgroups of…
Traditionally Bayesian decision-theoretic design of experiments proceeds by choosing a design to minimise expectation of a given loss function over the space of all designs. The loss function encapsulates the aim of the experiment, and the…
In Oncology, trials evaluating drug combinations are becoming more common. While combination therapies bring the potential for greater efficacy, they also create unique challenges for ensuring drug safety. In Phase-I dose escalation trials…
Approving and assessing new drugs is complex because multiple criteria must be considered simultaneously. A common approach is benefit-risk analysis, often conducted within a Bayesian framework to account for uncertainty and combine data…
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…
Drug discovery is a complex process that involves sequentially screening and examining a vast array of molecules to identify those with the target properties. This process, also referred to as sequential experimentation, faces challenges…
We propose an adaptive design for early phase drug combination cancer trials with the goal of estimating the maximum tolerated dose (MTD). A nonparametric Bayesian model, using beta priors truncated to the set of partially ordered dose…
Platform trials have become increasingly popular for drug development programs, attracting interest from statisticians, clinicians and regulatory agencies. Many statistical questions related to designing platform trials - such as the impact…
Dose-finding studies in oncology often include an up-and-down dose transition rule that assigns a dose to each cohort of patients based on accumulating data on dose-limiting toxicity (DLT) events. In making a dose transition decision, a key…
This paper introduces Bayesian frameworks for tackling various aspects of multi-criteria decision-making (MCDM) problems, leveraging a probabilistic interpretation of MCDM methods and challenges. By harnessing the flexibility of Bayesian…
We consider a dose-optimization design for first-in-human oncology trial that aims to identify a suitable dose for late-phase drug development. The proposed approach, called the Pharmacometrics-Enabled DOse OPtimization (PEDOOP) design,…
In this paper we consider two-stage adaptive dose-response study designs, where the study design is changed at an interim analysis based on the information collected so far. In a simulation study, two approaches will be compared for these…
Quantitative decision-making (QDM) principles address the issues related to the mapping of results to decisions, the synthesis of information and the quantification of uncertainty. Since the clinical drug development involves a succession…
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…
Combination of several anti-cancer treatments has typically been presumed to have enhanced drug activity. Motivated by a real clinical trial, this paper considers phase I-II dose finding designs for dual-agent combinations, where one main…
Power and sample size analysis comprises a critical component of clinical trial study design. There is an extensive collection of methods addressing this problem from diverse perspectives. The Bayesian paradigm, in particular, has attracted…
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…
We review typical design problems encountered in the planning of observational studies and propose a unifying framework that allows us to use the same concepts and notation for different problems. In the framework, the design is defined as…
Phase I-II cancer clinical trial designs are intended to accelerate drug development. In cases where efficacy cannot be ascertained in a short period of time, it is common to divide the study in two stages: i) a first stage in which dose is…