相关论文: Optimal Dosing Schedules for Substances Inducing T…

The primary objective of Phase I oncology trials is to assess the safety and tolerability of novel therapeutics. Conventional dose escalation methods identify the maximum tolerated dose (MTD) based on dose-limiting toxicity (DLT). However,…

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…

We propose an incentive scheme based on intervention to sustain cooperation among self-interested users. In the proposed scheme, an intervention device collects imperfect signals about the actions of the users for a test period, and then…

Over the past decade, several targeted therapies (e.g. imatinib, dasatinib, nilotinib) have been developed to treat Chronic Myeloid Leukemia (CML). Despite an initial response to therapy, drug resistance remains a problem for some CML…

We study the problem of a decision maker who must provide the best possible treatment recommendation based on an experiment. The desirability of the outcome distribution resulting from the policy recommendation is measured through a…

The use of `backfilling', assigning additional patients to doses deemed safe, in phase I dose-escalation studies has been used in practice to collect additional information on the safety profile, pharmacokinetics and activity of a drug.…

While kidney transplants are seen as the best treatment option for patients with end-stage renal disease and kidney failure, the organ's health depends on the dosage of immunosuppressant drugs post-transplantation. Due to the dosage…

Studies of alcohol and drug use are often interested in the number of days that people use the substance of interest over an interval, such as 28 days before a survey date. Although count models are often used for this purpose, they are not…

We consider design issues for toxicology studies when we have a continuous response and the true mean response is only known to be a member of a class of nested models. This class of non-linear models was proposed by toxicologists who were…

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…

Aims: Combinations of treatments can offer additional benefit over the treatments individually. However, trials of these combinations are lower priority than the development of novel therapies, which can restrict funding, timelines and…

Identification of optimal dose combinations in early phase dose-finding trials is challenging, due to the trade-off between precisely estimating the many parameters required to flexibly model the possibly non-monotonic dose-response…

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…

It is increasingly common for therapies in oncology to be given in combination. In some cases, patients can benefit from the interaction between two drugs, although often at the risk of higher toxicity. A large number of designs to conduct…

Optimization-based models have been used to predict cellular behavior for over 25 years. The constraints in these models are derived from genome annotations, measured macro-molecular composition of cells, and by measuring the cell's growth…

To better understand effects of exposure to food allergens, food challenge studies are designed to slowly increase the dose of an allergen delivered to allergic individuals until an objective reaction occurs. These dose-to-failure studies…

Dose optimization is a hallmark of Project Optimus for oncology drug development. The number of doses to include in a dose optimization study depends on the totality of evidence, which is often unclear in early-phase development. With equal…

In toxicology research, experiments are often conducted to determine the effect of toxicant exposure on the behavior of mice, where mice are randomized to receive the toxicant or not. In particular, in fixed interval experiments, one…

Optimal treatment rules can improve health outcomes on average by assigning a treatment associated with the most desirable outcome to each individual. Due to an unknown data generation mechanism, it is appealing to use flexible models to…

Two useful strategies to speed up drug development are to increase the patient accrual rate and use novel adaptive designs. Unfortunately, these two strategies often conflict when the evaluation of the outcome cannot keep pace with the…