When an investigational in vitro diagnostic is used to select which patients will receive an investigational compound in a clinical trial, often an IDE is needed because the test result is determining whether a patient will be included or excluded from a particular study. In the past, the information about the IVD has been included in the IND for Phase I and some Phase II trials. However, in the past year or so, OIR has often been requesting that we file a separate IDE so the Agency has more information about the diagnostic product. The IDE route also seems to facilitate review of the diagnostic (i.e., CDRH doesn't have to go over to CDER to review the documents).
There seems to be general agreement that filing an IDE is right approach when preparing for a trial that is registrational (i.e., Phase 3 and some Phase 2 studies). The isssue of whether an IDE is needed in early clincial trial work (Phase 1 and early Phase 2) is more difficult to answer. It is also becoming a more pressing question as the rise in the number of trials where patients are selected by a biomarker in early phase trials is on the rise.
The experience so far on whether IDEs are required for early stage trials feels a little like visiting a casino to play roulette or the slots. It seems a bit more based on the individuals involved rather than a defined policy. We've recently had experiences ranging from being allowed to send in a product insert for the IVD as a supplement to the IND all the way to preparing full IDEs that are submitted separately to CDRH.
This sort of unpredictabiity is to be expected given the dynamic nature of CoDx programs and policy at this moment in time. We also have no doubt the policies will gel over the next couple of years. In the meantime, we offer the following general advice when an IVD will be used to select patients for a trial:
- For non-registrational trials, likely filing information for the IVD in the IND will be sufficient. We suggest more than a product insert but not as much as an IDE. Giving FDA information on the device cut-off and some data for early analytical studies seems to be about right.
- For a trial that is designed to be non-registrational but may become registrational based on a Breakthrough designation, we suggest a more thorough approach. For these products we strongly suggest working closely with OIR via pre-submissions and determining during those discussions whether an IDE is needed or recommended. The decisions will be based on the safety profile of the drug along with the specifics on why certain patients are being selected for the trial.
- For Phase 3 trials with a selected design, it's best these days to just assume an IDE will be needed. There are hypothetical cases we can come up with where it may not be needed, but the input and feedback from OIR on the IVD are well worth the time and effort.