Related papers: Next generation clinical trials: Seamless designs …
Adaptive seamless designs combine confirmatory testing, a domain of phase III trials, with features such as treatment or subgroup selection, typically associated with phase II trials. They promise to increase the efficiency of development…
The use of drug combinations in clinical trials is increasingly common during the last years since a more favorable therapeutic response may be obtained by combining drugs. In phase I clinical trials, most of the existing methodology…
The traditional more-is-better dose selection paradigm, developed based on cytotoxic chemotherapeutics, is often problematic When applied to the development of novel molecularly targeted agents (e.g., kinase inhibitors, monoclonal…
There has been an increasing use of master protocols in oncology clinical trials because of its efficiency and flexibility to accelerate cancer drug development. Depending on the study objective and design, a master protocol trial can be a…
The US FDA's Project Optimus initiative that emphasizes dose optimization prior to marketing approval represents a pivotal shift in oncology drug development. It has a ripple effect for rethinking what changes may be made to conventional…
Due to the high cost and high failure rate of Phase III trials, seamless Phase II/III designs are more and more popular to trial efficiency. A potential attraction of Phase II/III design is to allow a randomized proof-of-concept stage prior…
Clinical trials are an indispensable part of the drug development process, bridging the gap between basic research and clinical application. During the development of new drugs, clinical trials are used not only to evaluate the safety and…
Breakthroughs in cancer biology have defined new research programs emphasizing the development of therapies that target specific pathways in tumor cells. Innovations in clinical trial design have followed with master protocols defined by…
Clinical trials are pivotal in the drug discovery process to determine the safety and efficacy of a drug candidate. The high failure rates of these trials are attributed to deficiencies in clinical model development and protocol design.…
Recently, numerous pharmaceutical sponsors have expressed a great deal of interest in the development of biosimilars, which requires clinical trials to demonstrate the equivalence of pharmacokinetics (PK) and clinical efficacy.…
An early phase clinical trial is the first step in evaluating the effects in humans of a potential new anti-disease agent or combination of agents. Usually called "phase I" or "phase I/II" trials, these experiments typically have the…
It is increasingly common for therapies in oncology to be given in combination. In some cases, patients can benefit from the interaction between two drugs, although often at the risk of higher toxicity. A large number of designs to conduct…
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…
2-in-1 design (Chen et al. 2018) is becoming popular in oncology drug development, with the flexibility of using different endpoints at different decision time. Based on the observed interim data, sponsors choose either to seamlessly…
When a novel treatment has successfully passed phase I, different options to design subsequent phase II trials are available. One approach is a single-arm trial, comparing the response rate in the intervention group against a fixed…
There is a growing interest in the implementation of platform trials, which provide the flexibility to incorporate new treatment arms during the trial and the ability to halt treatments early based on lack of benefit or observed…
Phase 1-2 designs provide a methodological advance over phase 1 designs for dose finding by using both clinical response and toxicity. A phase 1-2 trial still may fail to select a truly optimal dose. because early response is not a perfect…
We propose a two-stage design for a clinical trial with an early stopping rule for safety. We use different criteria to assess early stopping and efficacy. The early stopping rule is based on a criteria that can be determined more quickly…
The increasingly pressing demand of novel drugs (e.g., gene therapies for personalized cancer care, ever evolving vaccines) with unprecedented levels of personalization, has put a remarkable pressure on the traditionally long time required…
A master protocol trial uses a single overarching protocol to test multiple therapies, often across several diseases or subtypes. Although such trials offer considerable flexibility and efficiency, their constrained and non-uniform…