Episode #11
Your CRO Called It Adverse. Now What?
The word "adverse" appears in your study report and the room goes quiet. Most founders treat it like a verdict. It isn't. It's a scientific conclusion — and it's one you need to own, understand, and be ready to defend when FDA asks about it. In this episode, we walk through the five-question framework for evaluating any toxicology finding, and explain the difference between a finding that limits your program and a finding that doesn't. Key takeaways: "Adverse" is not a label your CRO assigns and walks away from — it's a scientific starting point that requires your interpretation and defense An elevated liver enzyme at the high dose might be adverse, or it might be an adaptive response — and that distinction directly determines your NOAEL and safety margin The five questions: Is there a dose response? Is it reversible? Does histopath confirm it? Is the magnitude biologically significant? Is it consistent across sexes and species? A non-adverse call requires just as much documented rigor as an adverse finding — "we don't think it's adverse" is not a regulatory argument An adverse finding doesn't kill your program. An adverse finding with no interpretation, no context, and no safety argument does Links: The Complete Guide to Nonclinical Development: https://www.nonclinical.academy/ Work with Dessi: dessimcentee.com Subscribe to the newsletter: https://the-nonclinical.com/ The Nonclinical is hosted by Dessi McEntee, MS, DABT — board-certified toxicologist and Fractional Head of Toxicology. Subscribe to the newsletter on LinkedIn, take the course at nonclinical.academy, or work with Dessi at toxistrategy.com.
