Related papers: Flexible Seamless 2-in-1 Design with Sample Size A…

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)…

Designing messenger RNA (mRNA) sequences for a fixed target protein requires searching an exponentially large synonymous space while optimizing properties that affect stability and downstream performance. This is challenging because…

Composite binary endpoints are increasingly used as primary endpoints in clinical trials. When designing a trial, it is crucial to determine the appropriate sample size for testing the statistical differences between treatment groups for…

Technological advancements have made it possible to deliver mobile health interventions to individuals. A novel framework that has emerged from such advancements is the just-in-time adaptive intervention (JITAI), which aims to suggest the…

Dose optimization is a hallmark of Project Optimus for oncology drug development. The number of doses to include in a dose optimization study depends on the totality of evidence, which is often unclear in early-phase development. With equal…

In oncology, phase II studies are crucial for clinical development plans as such studies identify potent agents with sufficient activity to continue development in the subsequent phase III trials. Traditionally, phase II studies are…

In phase I dose escalation studies for dual-agent combinations, at least one drug often has an established monotherapy dose. Consequently, substantial prior clinical safety data often exist for one or more monotherapies, allowing the study…

A two-stage adaptive optimal design is an attractive option for increasing the efficiency of clinical trials. In these designs, based on interim data, the locally optimal dose is chosen for further exploration, which induces dependencies…

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…

Purpose: During discussions at the Data Science Roundtable meeting in Japan, there were instances where the adoption of the BOIN design was declined, attributed to the extension of study duration and increased sample size in comparison to…

The use and development of mobile interventions are experiencing rapid growth. In "just-in-time" mobile interventions, treatments are provided via a mobile device and they are intended to help an individual make healthy decisions "in the…

The FDA's Project Optimus initiative emphasizes patient-centered dose selection in oncology that balances efficacy and safety. We develop a framework for randomized dose optimization studies that uses clinically interpretable utility scores…

Survey researchers are increasingly turning to multimode data collection to deal with declines in survey response rates and increasing costs. An efficient approach offers the less costly modes (e.g., web) followed with a more expensive mode…

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…

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…

Conventionally, a first-in-human phase I trial in healthy volunteers aims to confirm the safety of a drug in humans. In such situations, volunteers should not suffer from any safety issues and simple algorithm-based dose-escalation schemes…

The efficiency of an experimental design is ultimately measured in terms of time and resources needed for the experiment. Optimal sequential (multi-stage) design is studied in the situation where each stage involves a fixed cost. The…

We consider conditional estimation in two-stage sample size adjustable designs and the following bias. More specifically, we consider a design which permits raising the sample size when interim results look rather promising, and, which…

Multi-stage (designed) procedures, obtained by splitting the sampling budget suitably across stages, and designing the sampling at a particular stage based on information about the parameter obtained from previous stages, are often…

Randomized discontinuation design (RDD) is an enrichment strategy commonly used to address limitations of traditional placebo-controlled trials, particularly the ethical concern of prolonged placebo exposure. RDD consists of two phases: an…