Seamless phase II/III trials

Published on December 29, 2016   40 min

A selection of talks on Pharmaceutical Sciences

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Today, we are going to be talking about Seamless Phase II/III Trials. My name is Elizabeth Garrett-Mayer and I'm an oncology biostatistician at the Hollings Cancer Center and the Department of Public Health Sciences at the Medical University of South Carolina. Along with me is Nathaniel O'Connell, who is a graduate student in the Department of Public Health Sciences. I will be giving the beginning part of this talk, and then towards the end, we will switch over and Nathaniel will finish the talk by going through some case study examples.
There are traditionally three phases of clinical trials. The first phase is often called a dose-finding study, where the goal is to find the optimal dose. These are commonly "first in man" trials and there are a range of doses that are evaluated to find the highest dose that falls below, or within, an acceptability threshold. These trials usually have relatively few patients and are completed as the first part of the clinical development of a drug. Moving on from phase I, after an optimal dose is found we go into the phase II setting. At this stage, the safety of the drug is further investigated and the efficacy of the drug is also investigated. These are more exploratory in nature, where we're looking to find what the correct dose, the regimen, or the schedule of the drug is. And they may investigate early efficacy across several dose levels, or treatments, or even regimens, or schedules. In this phase is where we're looking for the hint of efficacy to see whether or not the drug is showing sufficient promise to be moved forward to the next phase, which is phase III. In phase II we often allow relatively small sample sizes recognizing that we need preliminary evidence and it's not considered a definitive phase of drug development. The last phase of drug development in most contexts is phase III. In phase III it is a confirmatory stage where efficacy is determined, often versus a standard of care regimen. In these trials there is a large sample size relative to the phase II, and they are very often multi-site studies. Almost always are we going to be comparing a treatment to some kind of control group; And in this case we almost always have relatively strict error rates, meaning we need to have high statistical power and a low alpha level also known as the type 1 error rate. And this is because this stage is when there is the opportunity to have the drug approved by a federal agency, such as in the United States, the Federal Drug Administration.