Highlighting the Unique Challenges Presented by Device Trials in Heart Failure.

The Shark Tank presentations in this special focus issue of JACC: Basic to Translational Science highlight many of the unique difficulties that inventors and translational investigators face when designing early phase clinical trials with devices for treating heart failure. Dr Gregg Stone presented a talk at the Technology and Heart Failure Therapeutics (THT) 2022 conference: “Special Challenges of Heart Failure Device Trials.” His talk addressed a number of important issues that are unique to device trials, which I thought would provide context for many of the discussions in the Shark Tank presentations. Accordingly, I asked Gregg’s permission to include his THT 2022 presentation in the current special focus issue of JACC: Basic to Translational Science.

Dr Stone’s short (9:29 minute) presentation begins with a discussion of the essential elements for success in device trials. He began by pointing out that for a new device to gain traction it is not enough to obtain approval by the US Food and Drug Administration. Stone remarked that it is equally important to persuade the Centers for Medicare and Medicaid Services and insurance companies to pay for the device once it is approved, and it is even more important to convince doctors and patients that the device is safe and effective. Although these types of hurdles are not necessarily unique to device trials, they are especially important for devices, which often face strong headwinds in terms of gaining traction in the clinical marketplace. Dr Stone discussed the critical issue of having the proper control group in device trials, which can be extremely difficult for device trials that involve an invasive procedure. Indeed, it may not be possible to have a blinded trial with an implantable cardiac device either because it is unethical or impractical to use a sham control in the target patient population because of the inherent risk of implanting the control device. He mentioned that if the trial design does use a sham control device, it is important to assess the degree to which patients are blinded with respect to treatment assignment by performing an analysis of the efficacy of patient blinding.

Dr Stone also discussed the important issue of proper background therapy, which tends to get less emphasis in device trials than in drug trials. This concern is especially important in early phase II device trials, wherein the number of patients is limited, and small imbalances in background therapy can lead to important differences in the treatment and control arms that have little or nothing to do with the device that is being tested. He also reviewed the topic of primary end points for device trials, including having separate safety and effectiveness end points. The majority of his comments on end points were skewed toward larger pivotal device trials and were, therefore, less apposite for early phase I and phase II device trials discussed in the Shark Tank presentation. However, he did review the Finkelstein-Schoenfeld/Win ratio, which integrates hard and soft end points in a hierarchical composite, and is thus well suited for analyzing phase II device trials. His presentation concluded quite appropriately with a quote from George W. Bush: “Nobody said it was going to be easy, and nobody was right.” For those who are interested in learning about the important issues that go into designing robust device trials, in under 10 minutes, Gregg Stone’s THT 2022 presentation is as good as it gets!