Related papers: Joint TITE-CRM for Dual Agent Dose Finding Studies
Cell heterogeneity plays an important role in patient responses to drug treatments. In many cancers, it is associated with poor treatment outcomes. Many modern drug combination therapies aim to exploit cell heterogeneity, but determining…
The U.S. Food and Drug Administration (FDA) launched Project Optimus to shift the objective of dose selection from the maximum tolerated dose to the optimal biological dose (OBD), optimizing the benefit-risk tradeoff. One approach…
Hierarchical random effect models are used for different purposes in clinical research and other areas. In general, the main focus is on population parameters related to the expected treatment effects or group differences among all units of…
Dose-escalation trials in oncology drug development still today typically aim to identify 1-size-fits-all dose recommendations, as arbitrary quantiles of the toxicity thresholds evident in patient samples. In the late 1990s efforts to…
Combination drug therapies hold significant promise for enhancing treatment efficacy, particularly in fields such as oncology, immunotherapy, and infectious diseases. However, designing clinical trials for these regimens poses unique…
The landscape of dose-finding designs for phase I clinical trials is rapidly shifting in the recent years, noticeably marked by the emergence of interval-based designs. We categorize them as the iDesigns and the IB-Designs. The iDesigns are…
Non-adherence to assigned treatment is common in randomised controlled trials (RCTs). Recently, there has been an increased interest in estimating causal effects of treatment received, for example the so-called local average treatment…
A dynamic treatment regimen (DTR) is a pre-specified sequence of decision rules which maps baseline or time-varying measurements on an individual to a recommended intervention or set of interventions. Sequential multiple assignment…
Purpose: The early identification of maximum tolerated dose (MTD) in phase I trial leads to faster progression to a phase II trial or an expansion cohort to confirm efficacy. Methods: We propose a novel adaptive design for identifying MTD…
In the presence of heterogeneity between the randomized controlled trial (RCT) participants and the target population, evaluating the treatment effect solely based on the RCT often leads to biased quantification of the real-world treatment…
Cancer is one of the most common diseases worldwide, posing a serious threat to human health and leading to the deaths of a large number of people. It was observed during the drug administration in chemotherapy that immune cells, cancer…
Clinical trials are an instrument for making informed decisions based on evidence from well-designed experiments. Here we consider adaptive designs mainly from the perspective of multi-arm Phase II clinical trials, in which one or more…
Adaptive enrichment allows for pre-defined patient subgroups of interest to be investigated throughout the course of a clinical trial. Many trials which measure a long-term time-to-event endpoint often also routinely collect repeated…
This article proposes doubly robust estimators for the average treatment effect on the treated (ATT) in difference-in-differences (DID) research designs. In contrast to alternative DID estimators, the proposed estimators are consistent if…
In the drug repurposing approach, the chemically diverse and potentially safe molecules can be explored as therapeutic potential out of those originally targeted indications. However, the intellectual property rights, and competitive…
Cluster randomized trials (CRTs) randomly assign an intervention to groups of individuals (e.g., clinics or communities) and measure outcomes on individuals in those groups. While offering many advantages, this experimental design…
Identifying the interaction targets of bioactive compounds is a foundational element for deciphering their pharmacological effects. Target prediction algorithms equip researchers with an effective tool to rapidly scope and explore potential…
Summary points: - This article considers the combination of two binary or two time-to-event endpoints to form the primary composite endpoint for leading a trial. - It discusses the relative efficiency of choosing a composite endpoint over…
A key challenge in non-cooperative multi-agent systems is that of developing efficient planning algorithms for intelligent agents to interact and perform effectively among boundedly rational, self-interested agents (e.g., humans). The…
We propose a frequentist adaptive phase 2 trial design to evaluate the safety and efficacy of three treatment regimens (doses) compared to placebo for four types of helminth (worm) infections. This trial will be carried out in four…