New FDA Guidance for ADHD Drug Development:
Rationale, Requirements and Implications for Trial Design
There was a guidance put out to the field within the last six months about what the FDA wanted from companies developing products and what the development program should look like. This is specifically for stimulants, but it may have relevance for compounds that are similar to stimulants but not stimulants or even non-stimulants to a certain extent.
Presenters included Tiffany Farchione, MD, Director of the Division of Psychiatry at the FDA and the former Head of the Division of Psychiatric Products, Tom Lochran, MD. We then had a panel after their presentations, that included Len Adler, MD, Matthew Brams, MD, Steve Faraone, PhD and Sharon Wigal, PhD.
Discussed was the need for placebo controlled parallel group studies of samples that are not necessarily enriched for responders or individuals who tolerate the drug, so that the drug placebo contrast is protected from being oversubscribed by people who respond well or tolerate well. The discussions they’re having about how to best study stimulant drugs in preschool kids, meaning four and five year olds in whom the medications are commonly used. But it hasn’t been a required part of the development package to date. Those have been studied after marketing in Phase IV. And they’re trying to figure out how to best deal with that. They know about the complexities of studying the population. They are also addressing some of the technical difficulties of studying new formulations in a patient population that has trouble ingesting, that if you’re going to try and get PK samples and you’ve got to draw bloods, you’re not going to find a lot of preschoolers that want to have their blood drawn. So there’s some real challenges regarding conducting studies with preschoolers.
On the other hand, we know that ADHD often begins in that age range and certainly there are a lot of kids in that age range who are treated. So if they’re going to be treated, it’s important to study it so that you’re not getting off label treatments. And we know about, for example, their comparability and response and tolerability, potential differences in PK profile, things of that sort. They’re very interested in that. They are very interested in temporal characteristics of the drugs, particularly the stimulant drugs because, as you know, the long acting ones are labeled for once a day, but in fact they have variable duration profiles and so they’re interested in methodologies that allow them to better understand the temporal characteristics of the drug. They’re very interested in setting a standard for safety and tolerability assessments in which people are asked about those issues and we don’t only rely on spontaneously reported adverse events.