Related papers: A Bayesian Optimal Phase II Design for Randomized …
Delayed treatment effects on time-to-event outcomes have often been observed in randomized controlled studies of cancer immunotherapies. In the case of delayed onset of treatment effect, the conventional test/estimation approach using the…
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…
The I-SPY2 phase 2 clinical trial is a long-running platform trial that evaluates neoadjuvant treatments for locally advanced breast cancer, assigning subjects to novel agents using response-adaptive randomization. Recently, I-SPY2 was…
There has been an increasing interest in using interval-based Bayesian designs for dose finding, one of which is the modified toxicity probability interval (mTPI) method. We show that the decision rules in mTPI correspond to an optimal rule…
Most statistical tests for treatment effects used in randomized clinical trials with survival outcomes are based on the proportional hazards assumption, which often fails in practice. Data from early exploratory studies may provide evidence…
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…
Traditionally, the major objective in phase I trials is to identify a working-dose for subsequent studies, whereas the major endpoint in phase II and III trials is treatment efficacy. The dose sought is typically referred to as the maximum…
We model the interaction between the immune system and tumor cells including a time delay to simulate the time needed by the latter to develop a chemical and cell mediated response to the presence of the tumor. The results are compared with…
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.…
To achieve the goal of providing the best possible care to each patient, physicians need to customize treatments for patients with the same diagnosis, especially when treating diseases that can progress further and require additional…
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…
Recently, the strategy for dose optimization in oncology has shifted to conduct Phase 2 randomized controlled trials with multiple doses. Optimal biologic dose selection from Phase 1 trial data to determine candidate doses for Phase 2…
We propose to use Bayesian optimization (BO) to improve the efficiency of the design selection process in clinical trials. BO is a method to optimize expensive black-box functions, by using a regression as a surrogate to guide the search.…
Precision medicine has led to a paradigm shift allowing the development of targeted drugs that are agnostic to the tumor location. In this context, basket trials aim to identify which tumor types - or baskets - would benefit from the…
Response-adaptive randomization (RAR) can increase participant benefit in clinical trials, but also complicates statistical analysis. The burn-in period (a non-adaptive initial stage) is commonly used to mitigate this disadvantage, yet…
Dynamic treatment regimes in oncology and other disease areas often can be characterized by an alternating sequence of treatments or other actions and transition times between disease states. The sequence of transition states may vary…
Minimising cycle time without inducing quality defects is a major challenge in the injection moulding (IM). Design of Experiment methods (DoE) have been widely studied for optimisation of the IM, however existing methods have limitations,…
Radiation therapy treatment planning can be viewed as an iterative hyperparameter tuning process to balance conflicting clinical goals. In this work, we investigated the performance of modern Bayesian Optimization (BO) methods on automated…
Immune checkpoint therapy is one of the most promising immunotherapeutic methods that are likely able to give rise to durable treatment response for various cancer types. Despite much progress in the past decade, there are still critical…
Effectiveness of immune-oncology chemotherapies has been presented in recent clinical trials. The Kaplan-Meier estimates of the survival functions of the immune therapy and the control often suggested the presence of the lag-time until the…