The news that St. Jude Medical failed a futility analysis of its BROADEN trial of DBS for treatment of depression cast a pall over an otherwise upbeat attendance at the 2013 NANS meeting [see Conference Report, p7]. Once again, the industry is left to pick up the pieces as a promising new technology gets set back by what could be many years.
It’s too early to assess blame for this failure. It’s tempting to wonder if St. Jude management was too eager to commence this trial, since that has been a culprit in other trial failures. But there’s clearly more involved here, not least the complexity of specifying the precise brain circuits involved with major depression. Indeed, Helen Mayberg’s own thinking on DBS targeting has evolved over the years since the seminal paper she and colleague Andres Lozano published in Neuron in 2005, which implicated Cg25 as a lucrative target for depression. Mayberg now believes that neuronal tracts emanating from Cg25 toward medial frontal areas may be more relevant [NBR Nov13 p1]. Research that she, Cameron McIntyre, and others are conducting on probabilistic tractography to identify the patient-specific brain regions most relevant to the particular form of depression the patient is suffering from will likely prove to be very fruitful in the years ahead.
Rather than honing in on one target and placing all their eggs in one basket, neuromodulation vendors would be well advised to identify specific groups of patients who will most likely respond to a particular therapy during a clinical trial. If St. Jude management is to be criticized for anything, it should be for dropping the ball on the cortical stimulation technology for treating depression that it obtained for a song from Northstar Neuroscience after that firm’s failed stroke trial. The early depression data looked very promising and continuing the study might have yielded new information on the role cortical brain regions play in depression. Now it looks like that technology will revert back to Lozano’s group in Toronto.
Unfortunately, much of the progress in our understanding of DBS mechanisms in depression is potentially wasted without a vibrant installed base of patients and clinicians using and perfecting DBS therapies. As we saw with Parkinson’s disease, our understanding of the mechanisms of action of DBS increases with more procedures performed and with more patients using DBS. This in turn leads to a better understanding of the etiology of the disease. In our view, the FDA needs to understand the vital importance of getting first-generation devices into the field and move away from arbitrary standards like improving symptoms by 50 percent in 50 percent of the population. The notion that if we can’t help everybody we shouldn’t help anybody has no place in medical science, particularly when you consider that neuromodulation therapies are working with the hardest-case patients who have not responded to other therapies.
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