Related papers: Potential outcome simulation for efficient head-to…
The treatment assignment mechanism in a randomized clinical trial can be optimized for statistical efficiency within a specified class of randomization mechanisms. Optimal designs of this type have been characterized in terms of the…
Dose-finding studies are frequently conducted to evaluate the effect of different doses or concentration levels of a compound on a response of interest. Applications include the investigation of a new medicinal drug, a herbicide or…
Adaptive sample size re-estimation, early stopping, and trial re-design at interim analyses can reduce expected sample sizes in randomised trials. Cluster randomised trials, in which groups of participants are randomly allocated to…
Optimal design of a Phase I cancer trial can be formulated as a stochastic optimization problem. By making use of recent advances in approximate dynamic programming to tackle the problem, we develop an approximation of the Bayesian optimal…
Background: Advanced adaptive randomised clinical trials are increasingly used. Compared to their conventional counterparts, their flexibility may make them more efficient, increase the probability of obtaining conclusive results without…
Statistical methodology for the design and analysis of clinical Phase II dose response studies, with related software implementation, are well developed for the case of a normally distributed, homoscedastic response considered for a single…
With increasing interest in adaptive clinical trial designs, challenges are present to drug supply chain management which may offset the benefit of adaptive designs. Thus, it is necessary to develop an optimization tool to facilitate the…
Early phase, personalized dose-finding trials for combination therapies seek to identify patient-specific optimal biological dose (OBD) combinations, which are defined as safe dose combinations which maximize therapeutic benefit for a…
Adaptive approaches, allowing for more flexible trial design, have been proposed for individually randomized trials to save time or reduce sample size. However, adaptive designs for cluster-randomized trials in which groups of participants…
Phase II dose finding studies in clinical drug development are typically conducted to adequately characterize the dose response relationship of a new drug. An important decision is then on the choice of a suitable dose response function to…
Clinical trials are an integral component of medical research. Trials require careful design to, for example, maintain the safety of participants, use resources efficiently and allow clinically meaningful conclusions to be drawn. Adaptive…
Broadening eligibility criteria in cancer trials has been advocated to represent the true patient population more accurately. While the advantages are clear in terms of generalizability and recruitment, novel dose-finding designs are needed…
Clinical trials constitute a critical yet exceptionally challenging and costly stage of drug development (\$2.6B per drug), where protocols are encoded as complex natural language documents, motivating the use of AI systems beyond manual…
Nowadays, more and more clinical trials choose combinational agents as the intervention to achieve better therapeutic responses. However, dose-finding for combinational agents is much more complicated than single agent as the full order of…
We propose a new integrated phase I/II trial design to identify the most efficacious dose combination that also satisfies certain safety requirements for drug-combination trials. We first take a Bayesian copula-type model for dose finding…
Phase I oncology trials aim to identify a safe dose - often the maximum tolerated dose (MTD) - for subsequent studies. Conventional designs focus on population-level toxicity modeling, with recent attention on leveraging pharmacokinetic…
An important task in drug development is to identify patients, which respond better or worse to an experimental treatment. Identifying predictive covariates, which influence the treatment effect and can be used to define subgroups of…
In learning-phase clinical trials in drug development, adaptive designs can be efficient and highly informative when used appropriately. In this article, we extend the multiple comparison procedures with modeling techniques (MCP-Mod)…
In clinical trials, there is potential to improve precision and reduce the required sample size by appropriately adjusting for baseline variables in the statistical analysis. This is called covariate adjustment. Despite recommendations by…
We consider a dose-optimization design for first-in-human oncology trial that aims to identify a suitable dose for late-phase drug development. The proposed approach, called the Pharmacometrics-Enabled DOse OPtimization (PEDOOP) design,…