相关论文: Estimands for Early Phase Dose Optimization Trials…
A treatment regime is a deterministic function that dictates personalized treatment based on patients' individual prognostic information. There is a fast-growing interest in finding optimal treatment regimes to maximize expected long-term…
The effects of molecularly targeted drug perturbations on cellular activities and fates are difficult to predict using intuition alone because of the complex behaviors of cellular regulatory networks. An approach to overcoming this problem…
Dose-finding trials are a key component of the drug development process and rely on a statistical design to help inform dosing decisions. Triallists wishing to choose a design require knowledge of operating characteristics of competing…
Although there is an extensive statistical literature showing the disadvantages of discretizing continuous variables, categorization is a common practice in clinical research which results in substantial loss of information. A large…
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.…
Novel dose-finding designs, using estimation to assign the best estimated maximum- tolerated-dose (MTD) at each point in the experiment, most commonly via Bayesian techniques, have recently entered large-scale implementation in Phase I…
The estimand framework provides guidance on handling intercurrent events, such as treatment discontinuation, in the analysis of clinical trial responses. Under ICH E9(R1), the treatment policy (TP) strategy incorporates post-discontinuation…
The primary goal of dose allocation in phase I trials is to minimize patient exposure to subtherapeutic or excessively toxic doses, while accurately recommending a phase II dose that is as close as possible to the maximum tolerated dose…
In this article, we propose a phase I-II design in two stages for the combination of molecularly targeted therapies. The design is motivated by a published case study that combines a MEK and a PIK3CA inhibitors; a setting in which higher…
In response to the U.S.\ Food and Drug Administration's (FDA) Project Optimus, a paradigm shift is underway in the design of early-phase oncology trials. To accelerate drug development, seamless Phase I/II designs have gained increasing…
We present, as a pure Prolog program, the first executable specification of the 3 + 3 dose-escalation protocol commonly used in early-phase oncology drug development. In this program, the imperative operations of the protocol emerge as…
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 many applied optimization settings, parameters that define the constraints may not guarantee the best possible solution, and superior solutions might exist that are infeasible for the given parameter values. Removing such constraints,…
Nonlinear regression models addressing both efficacy and toxicity outcomes are increasingly used in dose-finding trials, such as in pharmaceutical drug development. However, research on related experimental design problems for corresponding…
This work introduces the Burdened Bayesian Logistic Regression Model (BBLRM), an enhancement of the Bayesian Logistic Regression Model (BLRM) for dose-finding in phase I oncology trials. The BLRM determines the maximum tolerated dose (MTD)…
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…
An accurately identified maximum tolerated dose (MTD) serves as the cornerstone of successful subsequent phases in oncology drug development. Bayesian logistic regression model (BLRM) is a popular and versatile model-based dose-finding…
An unprecedented number of new cancer targets are in development, and most are being developed in combination therapies. Early oncology development is strategically challenged in choosing the best combinations to move forward to late stage…
When to initiate treatment on patients is an important problem in many medical studies such as AIDS and cancer. In this article, we formulate the treatment initiation time problem for time-to-event data and propose an optimal individualized…
In oncology, phase II or multiple expansion cohort trials are crucial for clinical development plans. This is because they aid in identifying potent agents with sufficient activity to continue development and confirm the proof of concept.…