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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…
For simulation-based systems, finding a set of test cases with the least cost by exploring multiple goals is a complex task. Domain-specific optimization goals (e.g. maximize output variance) are useful for guiding the rapid selection of…
Executing various sequences of system functions in a system under test represents one of the primary techniques in software testing. The natural way to create effective, consistent and efficient test sequences is to model the system under…
Recent statistical and reinforcement learning methods have significantly advanced patient care strategies. However, these approaches face substantial challenges in high-stakes contexts, including missing data, inherent stochasticity, and…
Dynamic treatment regimes formalize precision medicine as a sequence of decision rules, one for each stage of clinical intervention, that map current patient information to a recommended intervention. Optimal regimes are typically defined…
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.…
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…
An individualized dose rule recommends a dose level within a continuous safe dose range based on patient level information such as physical conditions, genetic factors and medication histories. Traditionally, personalized dose finding…
There are multiple cluster randomised trial designs that vary in when the clusters cross between control and intervention states, when observations are made within clusters, and how many observations are made at that time point. Identifying…
Purpose: The early identification of maximum tolerated dose (MTD) in phase I trial leads to faster progression to a phase II trial or an expansion cohort to confirm efficacy. Methods: We propose a novel adaptive design for identifying MTD…
We propose a simulation-optimization-based methodology to improve the way that organ transplant offers are made to potential recipients. Our policy can be applied to all types of organs, is implemented starting at the local level, is…
We construct optimal designs for estimating fetal malformation rate, prenatal death rate and an overall toxicity index in a toxicology study under a broad range of model assumptions. We use Weibull distributions to model these rates and…
Clinical trials constitute a critical yet exceptionally challenging and costly stage of drug development (\$2.6B per drug), where protocols are encoded as complex natural language documents, motivating the use of AI systems beyond manual…
2-in-1 design (Chen et al. 2018) is becoming popular in oncology drug development, with the flexibility of using different endpoints at different decision time. Based on the observed interim data, sponsors choose either to seamlessly…
As a future trend of healthcare, personalized medicine tailors medical treatments to individual patients. It requires to identify a subset of patients with the best response to treatment. The subset can be defined by a biomarker (e.g.…
Minimizing the number of patients exposed to potentially harmful drugs in early onco logical trials is a major concern during planning. Adaptive designs account for the inherent uncertainty about the true effect size by determining the…
Group sequential designs (GSDs) are well established and the most commonly used adaptive design in confirmatory clinical trials with interim analyses. However, they remain underutilised, and their implementation involves unique theoretical…
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…
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…
The conventional phase II trial design paradigm is to make the go/no-go decision based on the hypothesis testing framework. Statistical significance itself alone, however, may not be sufficient to establish that the drug is clinically…