Name:
Kert Viele, PhD, discusses dose-finding trials and optimizing phase 2 data in the drug development process.
Description:
Kert Viele, PhD, discusses dose-finding trials and optimizing phase 2 data in the drug development process.
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Upload Date:
2022-02-28T00:00:00.0000000
Transcript:
Language: EN.
Segment:0 .
>> This is Ed Livingston, Deputy Editor for Clinical Reviews and Education at JAMA. I'm here with Dr. Kert Viele, who wrote a chapter in the JAMA Guide to Statistics and Methods on Dose Finding Trials. >> Can we start by having you tell us your name and title? >> My name is Kert Viele, I am a director and senior statistical scientist at Berry Consultants. >> Well, thank you for joining us. You wrote a chapter in the JAMA Guide to Statistics and Methods book, entitle Dose Finding Trials, Optimizing Phase 2 Data in the Drug Development Process.
Could you start by telling us about the different phases of clinical trials? >> Clinical trials are usually organized in three phases. The first one, phase 1, is aimed at finding a maximally tolerated dose, above which there might be safety issues. Phase 2 is usually used to refine a dose or a population. Dose finding was the purpose of our article. And phase 3 is used to confirm that, the assumptions that have been found in the previous phases.
>> Could you walk us through what a phase 2 trial is and how it's done? >> A phase 2 trial is usually of moderate size. Often the sample size is in the 10s to 100s. Usually there are multiple doses or multiple populations under consideration. The subjects within the trial would be randomized among multiple arms. And at the end of the study, the goal is to decide should the therapy be continued for further development and which arm or arms should be continued into that further development.
>> Now these are done to balance safety and efficacy for a drug, and to find the right does that achieves that balance. But generally you need a lot more patients to show safety than you do efficacy, so how do you balance those two major objectives of a phase 2 trial? >> So as you noted, usually you would pay more attention to efficacy, and part of the phase 3 trial would be to confirm safety with larger numbers, and also post marketing would be used for that purpose.
In phase 2, we would typically be alert to signals of a major safety concern. And that might be done during the study with the DSMB, or at the end of the study when there is a look at adverse events. >> Are there limitations of dose finding trials? >> Yes, certainly. There are-- The goal of dose finding, in general, is to find the proper does to go on to future development. Certainly, when you look at multiple doses, you could get that dose wrong.
And a common issue that you have to consider is the assumptions that go into your modeling. So if your model has assumptions about the form of the model, I assume that the dose response is linear and it happens to not be, then you would run into troubles and potentially pick a poor dose to go forward. >> For the average clinician who's reading a research article about reporting results of a phase 2 or dose finding trial, what aspects of that trial do you think are most important for those clinicians to look for?
>> You certainly want to see the data on all the individual doses. You would like to get an idea of the pattern among them. Is the efficacy generally trending up? Is it plateauing? Generally, those kind of qualitative features. You would also want to pay attention to the dose that was identified as being either the best, or often they would use something called an AD90, which simply means a dose where a plateau starts.
And you would also want to look at has there been any evidence of separation of that selected dose from the control. >> Is there anything else you think we should talk about for these trials? >> Certainly, I think the key aspect of dose finding trials is because of the uncertainty we often don't test enough doses. And dose models-- any kind of dose response modeling, would allow us to test larger numbers of doses and have a better chance of getting the right answer, while really not increasing the cost of trials.
>> Thanks for listening to this JAMAevidence podcast on the JAMA Guide to Statistics and Methods. For more information about this topic, go to jamaevidence.com, where you'll find a complete array of materials that will help you understand the medical literature. This is Ed Livingston, Deputy Editor for Clinical Reviews and Education at JAMA and coauthor of the book, The JAMA Guide to Statistics and Methods. Thanks for listening.
