Related papers: Precision Dose-finding Cancer Clinical Trials in t…
The complexity of human cancer often results in significant heterogeneity in response to treatment. Precision medicine offers potential to improve patient outcomes by leveraging this heterogeneity. Individualized treatment rules (ITRs)…
One of the challenges in the design of confirmatory trials is to deal with uncertainties regarding the optimal target population for a novel drug. Adaptive enrichment designs (AED) which allow for a data-driven selection of one or more…
Interval designs are a class of phase I trial designs for which the decision of dose assignment is determined by comparing the observed toxicity rate at the current dose with a prespecified (toxicity tolerance) interval. If the observed…
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…
In phase I dose escalation studies for dual-agent combinations, at least one drug often has an established monotherapy dose. Consequently, substantial prior clinical safety data often exist for one or more monotherapies, allowing the study…
It is crucial to design Phase II cancer clinical trials that balance the efficiency of treatment selection with clinical practicality. Sargent and Goldberg proposed a frequentist design that allow decision-making even when the primary…
Radiotherapy treatment planning often relies on time-consuming, trial-and-error adjustments that heavily depend on the expertise of specialists, while existing deep learning methods face limitations in generalization, prediction accuracy,…
Oncology drug development starts with a dose escalation phase to find the maximal tolerable dose (MTD). Dose limiting toxicity (DLT) is the primary endpoint for dose escalation phase. Traditionally, model-based dose escalation trial designs…
There is tremendous interest in precision medicine as a means to improve patient outcomes by tailoring treatment to individual characteristics. An individualized treatment rule formalizes precision medicine as a map from patient information…
Precision cancer medicine aims to determine the optimal treatment for each patient. In-vitro cancer drug sensitivity screens combined with multi-omics characterization of the cancer cells have become an important tool to achieve this aim.…
We propose a frequentist adaptive phase 2 trial design to evaluate the safety and efficacy of three treatment regimens (doses) compared to placebo for four types of helminth (worm) infections. This trial will be carried out in four…
Identifying the mutations that drive cancer growth is key in clinical decision making and precision oncology. As driver mutations confer selective advantage and thus have an increased likelihood of occurrence, frequency-based statistical…
Basket trials in oncology enroll multiple patients with cancer harboring identical gene alterations and evaluate their response to targeted therapies across cancer types. Several existing methods have extended a Bayesian hierarchical model…
Cancer cell lines have frequently been used to link drug sensitivity and resistance with genomic profiles. To capture genomic complexity in cancer, the Cancer Genome Project (CGP) (Garnett et al., 2012) screened 639 human tumor cell lines…
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…
In parametric Bayesian designs of early phase cancer clinical trials with drug combinations exploring a discrete set of partially ordered doses, several authors claimed that there is no added value in including an interaction term to model…
In Phase I/II dose-finding trials, the objective is to find the Optimal Biological Dose (OBD), a dose that is both safe and efficacious that maximises some optimality criterion based on safety and efficacy. This is further complicated when…
Drug repurposing identifies new therapeutic uses for existing drugs, reducing the time and costs compared to traditional de novo drug discovery. Most existing drug repurposing studies using real-world patient data often treat the entire…
Identifying subgroups of patients with an enhanced response to a new treatment has become an area of increased interest in the last few years. When there is knowledge about possible subpopulations with an enhanced treatment effect before…
An endeavor central to precision medicine is predictive biomarker discovery; they define patient subpopulations which stand to benefit most, or least, from a given treatment. The identification of these biomarkers is often the byproduct of…