The Lost Decade

For neuromodulation researchers, clinicians, and entrepreneurs pursuing the market for psychiatric disorders, the road to commercialization of new therapies has been long and bumpy. But as we indicate in our article on page 1 of this issue, the perseverance of those who did not give up the fight after some early setbacks seems like it has paid off.

This publication was the first to report on the failed futility analysis of the BROADEN clinical trial of DBS of area 25 for treatment-resistant depression [NBR Dec13 p7]. We confirmed with St. Jude Medical CEO Dan Starks that the company would be exiting the depression market. An excellent article in The Atlantic by science journalist David Dobbs in 2018 sheds more light on the events surrounding the trial failure.

While the FDA’s decision to grant breakthrough device designation to Abbott’s DBS therapy for treatment-resistant depression is encouraging, it begs the question as to why it wasn’t so breakthrough nine years ago. It seems likely that regulators failed to recognize the dramatically different time horizons with neuromodulation therapies compared to drug interventions. A six-month futility analysis might be relevant in a pharmaceutical trial but it clearly missed the boat in this and other neuromodulation trials. Numerous studies have shown that with neuromodulation, 12-month data is better than six-month data; 24-month data is better than 12-month data; 36-month data is better than 24-month data.

We also continue to highlight the fundamental unfairness of an arbitrary standard such as achieving 50 percent response in 50 percent of the treatment-resistant population—particularly given that pharma therapies had failed to help 30 percent or more of the population as a whole. Even a 10 percent responder rate in the treatment-resistant population might have saved the lives of thousands of severely depressed individuals for whom suicide was the only apparent option. If it turns out that Abbott’s DBS therapy is a viable alternative for people with TRD, the FDA will have a lot of explaining to do with the parents and loved ones of those lost during this lost decade. As we wrote in this space in 2013, the notion that if we can’t help everybody we shouldn’t help anybody has no place in a civilized society.

On a much less important note, former shareholders of St. Jude Medical might now be wondering how much more Abbott would have paid had the BROADEN trial produced a different result. That’s not really a factor that the FDA should consider in its decisions. But what it should keep in mind is that our understanding of the mechanisms of action of DBS therapy—and the etiology of the underlying disease—is enhanced with each new generation of implanted devices. We won’t gain that understanding if the first generation never sees the light of day.

James Cavuoto
Editor and Publisher