Related papers: Joint TITE-CRM for Dual Agent Dose Finding Studies
The main objective of dose finding trials is to find an optimal dose amongst a candidate set for further research. The trial design in oncology proceeds in stages with a decision as to how to treat the next group of patients made at every…
In a tie-breaker design (TBD), subjects with high values of a running variable are given some (usually desirable) treatment, subjects with low values are not, and subjects in the middle are randomized. TBDs are intermediate between…
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…
The traditional more-is-better dose selection paradigm, developed based on cytotoxic chemotherapeutics, is often problematic When applied to the development of novel molecularly targeted agents (e.g., kinase inhibitors, monoclonal…
In this work, we propose an approach to determine the dosages of antithyroid agents to treat hyperthyroid patients. Instead of relying on a trial-and-error approach as it is commonly done in clinical practice, we suggest to determine the…
The long-term efficacy of targeted therapeutics for cancer treatment can be significantly limited by the type of therapy and development of drug resistance, inter alia. Experimental studies indicate that the factors enhancing acquisition of…
In the era of targeted therapy, there has been increasing concern about the development of oncology drugs based on the "more is better" paradigm, developed decades ago for chemotherapy. Recently, the US Food and Drug Administration (FDA)…
An important objective in the development of targeted therapies is to identify the populations where the treatment under consideration has positive benefit risk balance. We consider pivotal clinical trials, where the efficacy of a treatment…
Candidate binary endpoints are often considered as surrogates for time-to-event (TTE) clinical endpoints, primarily because they can be assessed at earlier time points. To be submitted for regulatory approval candidate binary endpoints need…
Molecular docking is an essential tool for drug design. It helps the scientist to rapidly know if two molecules, respectively called ligand and receptor, can be combined together to obtain a stable complex. We propose a new multi-objective…
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…
Recent advancements in generative machine learning have enabled rapid progress in biological design tools (BDTs) such as protein structure and sequence prediction models. The unprecedented predictive accuracy and novel design capabilities…
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.…
The primary object of a phase I clinical trial is to determine the maximum tolerated dose (MTD). Typically, the MTD is identified using a dose-escalation study, where initial subjects are treated at the lowest dose level and subsequent…
Advancements in large language models (LLMs) allow them to address diverse questions using human-like interfaces. Still, limitations in their training prevent them from answering accurately in scenarios that could benefit from multiple…
Phase I dose-finding studies aim at identifying the maximal tolerated dose (MTD). It is not uncommon that several dose-finding studies are conducted, although often with some variation in the administration mode or dose panel. For instance,…
Significant evidence has become available that emphasizes the importance of personalization in medicine. In fact, it has become a common belief that personalized medicine is the future of medicine. The core of personalized medicine is the…
Biomarker-guided designs are increasingly used to evaluate personalized treatments based on patients' biomarker status in Phase II and III clinical trials. With adaptive enrichment, these designs can improve the efficiency of evaluating the…
Randomized clinical trials (RCTs) are ideal for estimating causal effects, because the distributions of background covariates are similar in expectation across treatment groups. When estimating causal effects using observational data,…
A 'dual-field' strategy is often used for tumors with highly complex shapes and/or with large volumes exceeding available field-size in both passive and scanning irradiations with ion beams. Range and setup uncertainties can cause hot and…