Novel Trial Design Focus AllComers Studies FDA View

Novel Trial Design Focus: All-Comers Studies: FDA View Ashley B. Boam, MSBE Chief Interventional Cardiology Devices Branch FDA/CDRH/ODE/DCD DHHS/FDA

DISCLOSURES Ashley Boam I have no real or apparent conflicts of interest to report.

The “All-Comers” Clinical Trial Recent enthusiasm for the concept of all-comers trials Randomize all patients eligible for PCI with a DES – Easier to enroll than a restricted subpopulation Overall primary endpoint analysis of pooled population Appeal is (seemingly) straightforward conclusion: “In an all-comers trial, the XX DES was noninferior to the YY DES. ” DHHS/FDA

But… DHHS/FDA

Limitations Not all patients/lesions fall within approved indications for the control DES “Eligible for PCI with DES” does not always equal standard of care – For left main disease, 3 -vessel disease, very long lesions (>40 mm), DM + 2/3 VD standard of care is CABG – Bifurcation disease – no approved PCI device for bifurcation treatment – Control DES could have a clinically unacceptable outcome, but if the new DES were non-inferior, would be considered a “win” Primary endpoint estimates and sample size dependent on final case mix DHHS/FDA

Limitations Studies not typically powered for multiple subset analyses – How to interpret study results if different subsets yield different outcomes, but the overall result is still non-inferiority – All subsets would be underpowered to draw any conclusions Study design does not support a specific indication for labeling – Indications for use. A general description of the disease or condition the device will diagnose, treat, prevent, cure, or mitigate, including a description of the patient population for which the device is intended. (21 CFR 814. 20(b)(3)(i)) – “patients deemed suitable for PCI” is not an adequate description of the patient population DHHS/FDA

How can this approach be used? FDA is open to a trial with a broader patient population – Exclude those patients where CABG is clearly standard of care – Exclude patients with STEMI or enroll with separate randomization – Alternatively, enroll these patients in side registry to assess potential for separate randomized trial Primary endpoint - TLF at 12 months Add major secondary endpoints for certain subsets with specific hypotheses and method to address multiplicity (e. g. , sequential testing) – Need to confirm outcomes are “in the right direction” for certain important subsets – Allow wider margins of non-inferiority, or compare to performance goal as appropriate DHHS/FDA

Contact Information Ashley Boam ashley. boam@fda. hhs. gov 301 -796 -6341 DHHS/FDA