Related papers: Precision Dose-finding Cancer Clinical Trials in t…
Subclassification and matching are often used in empirical studies to adjust for observed covariates; however, they are largely restricted to relatively simple study designs with a binary treatment and less developed for designs with a…
When a novel treatment has successfully passed phase I, different options to design subsequent phase II trials are available. One approach is a single-arm trial, comparing the response rate in the intervention group against a fixed…
Traditional phase I dose finding cancer clinical trial designs aim to determine the maximum tolerated dose (MTD) of the investigational cytotoxic agent based on a single toxicity outcome, assuming a monotone dose-response relationship.…
The FDA's Project Optimus initiative emphasizes patient-centered dose selection in oncology that balances efficacy and safety. We develop a framework for randomized dose optimization studies that uses clinically interpretable utility scores…
We introduce a new multiple type I error criterion for clinical trials with multiple populations. Such trials are of interest in precision medicine where the goal is to develop treatments that are targeted to specific sub-populations…
Cancer and healthy cells have distinct distributions of molecular properties and thus respond differently to drugs. Cancer drugs ideally kill cancer cells while limiting harm to healthy cells. However, the inherent variance among cells in…
For many years Phase I and Phase II clinical trials were conducted separately, but there was a recent shift to combine these Phases. While a variety of Phase~I/II model-based designs for cytotoxic agents were proposed in the literature,…
The essence of precision oncology lies in its commitment to tailor targeted treatments and care measures to each patient based on the individual characteristics of the tumor. The inherent heterogeneity of tumors necessitates gathering…
With medical tests becoming increasingly available, concerns about over-testing and over-treatment dramatically increase. Hence, it is important to understand the influence of testing on treatment selection in general practice. Most…
Cluster randomized trials (CRTs) are studies where treatment is randomized at the cluster level but outcomes are typically collected at the individual level. When CRTs are employed in pragmatic settings, baseline population characteristics…
The Galleri (R) (GRAIL) multi-cancer early detection test measures circulating tumour DNA (ctDNA) to predict the presence of more than 50 different cancers, from a blood test. If sensitivity of the test to detect early-stage cancers is…
In oncology dose-finding trials, due to staggered enrollment, it might be desirable to make dose-assignment decisions in real-time in the presence of pending toxicity outcomes, for example, when the dose-limiting toxicity is late-onset.…
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…
Cell heterogeneity plays an important role in patient responses to drug treatments. In many cancers, it is associated with poor treatment outcomes. Many modern drug combination therapies aim to exploit cell heterogeneity, but determining…
Precision medicine is an emerging field that takes into account individual heterogeneity to inform better clinical practice. In clinical trials, the evaluation of treatment effect heterogeneity is an important component, and recently, many…
Developing targeted therapies based on patients' baseline characteristics and genomic profiles such as biomarkers has gained growing interests in recent years. Depending on patients' clinical characteristics, the expression of specific…
Model-assisted interval designs such as the Keyboard design are transparent and easy to implement in phase I oncology trials. However, interim decisions based solely on data from the current dose may overlook informative signals from…
In the era of precision medicine, more and more clinical trials are now driven or guided by biomarkers, which are patient characteristics objectively measured and evaluated as indicators of normal biological processes, pathogenic processes,…
Cancer is one of the most common diseases worldwide, posing a serious threat to human health and leading to the deaths of a large number of people. It was observed during the drug administration in chemotherapy that immune cells, cancer…
The Project Optimus initiative by the FDA's Oncology Center of Excellence is widely viewed as a groundbreaking effort to change the $\textit{status quo}$ of conventional dose-finding strategies in oncology. Unlike in other therapeutic areas…