Navigating FDA Feedback on Clinical Protocols: Key Considerations
Handling FDA feedback on original clinical protocols is a pivotal aspect of advancing a new therapy, with significant implications for your investigational new drug (IND) application and overall program direction. We wanted to highlight two crucial areas where the FDA and other Health Authorities commonly provide feedback on clinical protocols.
Starting Dose Justification: The starting dose is a foundational element of any clinical trial. While you may believe your chosen starting dose is well-justified in your submission, be prepared for the FDA's potential request to begin at a lower dose and work up to the therapeutic range. Adjusting the starting dose for studies with healthy volunteers is typically straightforward, involving the inclusion of a few lower dose levels in the escalation plan. In patient-focused studies, like oncology programs, the starting dose takes on critical significance. Here, you may have an opportunity to defend your proposed starting dose by highlighting its potential for clinical benefit. A compromise option is to consider an accelerated escalation design, initiating dosing at lower levels in single patients and swiftly moving into the therapeutic range if safety signals are clear.
Dose-Limiting Toxicity (DLT) Criteria: Another area where FDA feedback often comes into play is DLT criteria. It's worth noting that the FDA often suggests simplified criteria that may differ from the sponsor's initial proposal. Generally, accepting the FDA's suggested changes is a prudent course of action as it reduces the risk of protracted negotiations.
At Acumen, we advocate for a collaborative approach when working with Health Authorities. Our experience has shown that clients benefit from open and constructive dialogue with regulators. This includes accepting changes that do not significantly impact the program or trial design while advocating with clear and thoughtful communication when necessary.
Justin McLaughlin