Related papers: Two-dose vs. Three-Dose Optimization Under Sample …
One common approach for dose optimization is a two-stage design, which initially conducts dose escalation to identify the maximum tolerated dose (MTD), followed by a randomization stage where patients are assigned to two or more doses to…
Dose-escalation trials in oncology drug development still today typically aim to identify 1-size-fits-all dose recommendations, as arbitrary quantiles of the toxicity thresholds evident in patient samples. In the late 1990s efforts to…
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.…
Recently, the strategy for dose optimization in oncology has shifted to conduct Phase 2 randomized controlled trials with multiple doses. Optimal biologic dose selection from Phase 1 trial data to determine candidate doses for Phase 2…
Agent-based simulation with a synthetic population can help us compare different treatment conditions while keeping everything else constant within the same population (i.e., as digital twins). Such population-scale simulations require…
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…
There is a movement in design of experiments away from the classic randomization put forward by Fisher, Cochran and others to one based on optimization. In fixed-sample trials comparing two groups, measurements of subjects are known in…
We study the problem of finding the optimal dosage in early stage clinical trials through the multi-armed bandit lens. We advocate the use of the Thompson Sampling principle, a flexible algorithm that can accommodate different types of…
We consider the optimal design problem for identifying effective dose combinations within drug combination studies where the effect of the combination of two drugs is investigated. Drug combination studies are becoming increasingly…
Decision-making in personalized medicine such as cancer therapy or critical care must often make choices for dosage combinations, i.e., multiple continuous treatments. Existing work for this task has modeled the effect of multiple…
Consider a setup in which a decision maker is informed about the population by a finite sample and based on that sample has to decide whether or not to apply a certain treatment. We work out finite sample minimax regret treatment rules…
The literature on "mechanism design from samples," which has flourished in recent years at the interface of economics and computer science, offers a bridge between the classic computer-science approach of worst-case analysis (corresponding…
An objective of phase I dose-finding trials is to find the maximum tolerated dose; the dose with a particular risk of toxicity. Frequently, this risk is assessed across the first cycle of therapy. However, in oncology, a course of treatment…
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…
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,…
The principle of allocating an equal number of patients to each arm in a randomized controlled trial remains widely believed to be optimal for maximising statistical power. However, this long-held belief only holds true if the treatment…
Broadening eligibility criteria in cancer trials has been advocated to represent the true patient population more accurately. While the advantages are clear in terms of generalizability and recruitment, novel dose-finding designs are needed…
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…
Early phase, personalized dose-finding trials for combination therapies seek to identify patient-specific optimal biological dose (OBD) combinations, which are defined as safe dose combinations which maximize therapeutic benefit for a…
We consider the optimal strategy for laboratory testing of biological samples when we wish to know the results for each sample rather than the average prevalence of positive samples. If the proportion of positive samples is low considerable…