Related papers: Estimands for Early Phase Dose Optimization Trials…

While cancer has traditionally been considered a genetic disease, mounting evidence indicates an important role for non-genetic (epigenetic) mechanisms. Common anti-cancer drugs have recently been observed to induce the adoption of…

Consider an experiment, where a new drug is tested for the first time on human subjects - healthy volunteers. Such experiments are often performed as dose-escalation studies: a set of increasing doses is pre-selected, individuals are…

Observational studies provide the only evidence on the effectiveness of interventions when randomized controlled trials (RCTs) are impractical due to cost, ethical concerns, or time constraints. While many methodologies aim to draw causal…

A general framework is proposed for Bayesian model-based designs of Phase I cancer trials, in which a general criterion for coherence (Cheung, 2005) of a design is also developed. This framework can incorporate both "individual" and…

Leveraging preclinical animal data for a phase I first-in-man trial is appealing yet challenging. A prior based on animal data may place large probability mass on values of the dose-toxicity model parameter(s), which appear infeasible in…

Any process in which competing solutions replicate with errors and numbers of their copies depend on their respective fitnesses is the evolutionary optimization process. As during carcinogenesis mutated genomes replicate according to their…

Randomized controlled trials (RCT) are the gold standard for evaluation of the efficacy and safety of investigational interventions. If every patient in an RCT were to adhere to the randomized treatment, one could simply analyze the…

Modern clinical trials and cohort studies gather low-cost data on all participants but may have limited resources to assess expensive exposures such as biomarkers or genomic data. When interest lies in associations involving expensive…

The ICH E9(R1) addendum provides guidelines on accounting for intercurrent events in clinical trials using the estimands framework. However, there has been limited attention to the estimands framework for meta-analysis. Using treatment…

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…

If explicit, formal consideration of clinical pharmacology at all informs the design and conduct of modern oncology dose-finding trials, the designs themselves hardly attest to this. Yet in conducting a trial, investigators affirm that they…

Intensity Modulated Radiation Therapy is an effective cancer treatment. Models based on the Generalized Equivalent Uniform Dose (gEUD) provide radiation plans with excellent planning target volume coverage and low radiation for organs at…

The U.S. Food and Drug Administration (FDA) launched Project Optimus to shift the objective of dose selection from the maximum tolerated dose to the optimal biological dose (OBD), optimizing the benefit-risk tradeoff. One approach…

Optimal treatment regimes (OTR) are individualised treatment assignment strategies that identify a medical treatment as optimal given all background information available on the individual. We discuss Bayes optimal treatment regimes…

The dose delivered to the planning target volume by proton beams is highly conformal, sparing organs at risk and normal tissues. New treatment planning systems adapted to spot scanning techniques have been recently proposed to…

We propose a prognostic stratum matching framework that addresses the deficiencies of Randomized trial data subgroup analysis and transforms ObservAtional Data to be used as if they were randomized, thus paving the road for precision…

This paper presents a quasi-sequential optimal design framework for toxicology experiments, specifically applied to sea urchin embryos. The authors propose a novel approach combining robust optimal design with adaptive, stage-based testing…

Questions of `how best to acquire data' are essential to modeling and prediction in the natural and social sciences, engineering applications, and beyond. Optimal experimental design (OED) formalizes these questions and creates…

Although optimal control theory has been used for the theoretical study of anti-cancerous drugs scheduling optimization, with the aim of reducing the primary tumor volume, the effect on metastases is often ignored. Here, we use a previously…

Estimation of individual treatment effects is commonly used as the basis for contextual decision making in fields such as healthcare, education, and economics. However, it is often sufficient for the decision maker to have estimates of…