相关论文: Evaluating hybrid controls methodology in early-ph…
The development of oncology drugs progresses through multiple phases, where after each phase a decision is made about whether to move a molecule forward. Early phase efficacy decisions are often made on the basis of single arm studies based…
Individualized treatment decisions can improve health outcomes, but using data to make these decisions in a reliable, precise, and generalizable way is challenging with a single dataset. Leveraging multiple randomized controlled trials…
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…
The complementary information found in different modalities of patient data can aid in more accurate modelling of a patient's disease state and a better understanding of the underlying biological processes of a disease. However, the…
Dual agent dose-finding trials study the effect of a combination of more than one agent, where the objective is to find the Maximum Tolerated Dose Combination (MTC), the combination of doses of the two agents that is associated with a…
In this paper, an iterative method for real-time hybrid testing (RTHT) is proposed. The method seeks to iteratively balance the interface conditions between the physical and numerical substructures by controlling the periodic demand of the…
A platform trial with a master protocol provides an infrastructure to ethically and efficiently evaluate multiple treatment options in multiple diseases. Given that certain study drugs can enter or exit a platform trial, the randomization…
Toxicity monitoring is essential in Phase II clinical trials to ensure participant safety. While monitoring rules are well-established for single-arm trials, two-cohort trials present unique challenges because toxicities are expected to be…
Estimating intervention effects in dynamical systems is crucial for outcome optimization. In medicine, such interventions arise in physiological regulation (e.g., cardiovascular system under fluid administration) and pharmacokinetics, among…
Externally controlled trials (ECTs) are increasingly used when randomized controls are infeasible, unethical, or insufficient, including applications in rare diseases, oncology, pediatrics, and post-approval effectiveness research. Although…
There is growing interest in a hybrid control design for treatment evaluation, where a randomized controlled trial is augmented with external control data from a previous trial or a real world data source. The hybrid control design has the…
Phase I-II cancer clinical trial designs are intended to accelerate drug development. In cases where efficacy cannot be ascertained in a short period of time, it is common to divide the study in two stages: i) a first stage in which dose is…
While the use of combination therapy is increasing in prevalence for cancer treatment, it is often difficult to predict the exact interactions between different treatment forms, and their synergistic/antagonistic effects on patient health…
There are several different modalities, e.g., surgery, chemotherapy, and radiotherapy, that are currently used to treat cancer. It is common practice to use a combination of these modalities to maximize clinical outcomes, which are often…
Copula mixed models for trivariate (or bivariate) meta-analysis of diagnostic test accuracy studies accounting (or not) for disease prevalence have been proposed in the biostatistics literature to synthesize information. However, many…
The standard paradigm for confirmatory clinical trials is to compare experimental treatments with a control, for example the standard of care or a placebo. However, it is not always the case that a suitable control exists. Efficient…
A/B tests, also known as randomized controlled experiments (RCTs), are the gold standard for evaluating the impact of new policies, products, or decisions. However, these tests can be costly in terms of time and resources, potentially…
With the recent paradigm shift from cytotoxic drugs to new generation of target therapy and immuno-oncology therapy during oncology drug developments, patients with various cancer (sub)types may be eligible to participate in a basket trial…
In oncology phase I trials, model-assisted designs have been increasingly adopted because they enable adaptive yet operationally simple dose adjustment based on accumulating safety data, leading to a paradigm shift in dose-escalation…
Background: Phase I trials desire to identify the maximum tolerated dose (MTD) early and proceed quickly to an expansion cohort or phase II trial for efficacy. We propose an early completion method based on multiple dosages to accelerate…