Device dilemmas

Last month it was renal denervation. This month it is transcatheter aortic valve replacement (TAVR). Add to that revelations about devices approved for use in children for reasons to take pause.

The SYMPLICITY HTN-3 clinical trial’s negative findings came as a disappointment for physicians and patients who hoped that renal denervation would serve as an effective treatment for reducing hypertension in people who didn’t respond to aggressive medical therapy. The sham-controlled trial was much more rigorous than previous studies that found benefit. All have established safety, but HTN-3 didn’t meet its efficacy endpoint.

Another technology may be hitting a wall soon. This week a judge issued a preliminary injunction limiting the sale of Medtronic’s CoreValve TAVR device in a patent lawsuit filed by competitor Edwards Lifesciences. Edwards, which makes the Sapien TAVR system, argued that Medtronic infringed on its patent.

The court has allowed a brief delay before instituting the injunction and Medtronic filed an emergency motion to stay the injunction.

Both Sapien and CoreValve devices have been approved by the FDA as a treatment for inoperable patients with severe aortic stenosis. They are the only two devices approved in the U.S. Most likely some physicians, patients and payers are feeling consternation now. Having options is good but patent infringement can’t be allowed, if that is how the final judgment falls.

Also this week, researchers published a study in the journal Pediatrics that examined the FDA’s process for class III, or high-risk, devices approved for children. More than half of the 25 devices that received approval between 2008 and 2011 were for cardiovascular therapies. Approval for almost all of the 25 devices was based on an adult population, with only a few involving patients younger than 18 years old.

The authors reviewed premarket approval and humanitarian device exemption filings, which are two pathways for device approval. They wrote that some of the trials defined as pivotal by the FDA in these applications were observational and registry-based trials. Many of the trials were nonrandomized, open-label design with surrogate endpoints. 

In their discussion, they emphasized that—unlike pharmaceuticals—randomized, controlled clinical trials are rarely required for device approvals, “which is concerning because many devices are implanted and are more difficult to discontinue than drugs.”

HTN-3’s legacy may be the lesson it provided: What appears to be gold in observational, registry-based and even some randomized trials may lose its glitter when put to the highest standard of testing. This may be even more of a concern when it involves devices approved for children that weren’t evaluated in children.

It is a dilemma that should be watched vigilantly.

Candace Stuart

Cardiovascular Business, editor