As well as looking at the 40 percent improvement target, the Broaden team were also keen to see how many patients would achieve full remission; would they match the rates seen in Mayberg’s open-label work?
None of it happened. In late 2012, when the team finally had six months of data on 90 patients, the depression-score reductions weren’t even close. Of the 60 active patients, only 20 percent (12 of them) had reduced their scores the desired 40 percent after six months, and only 5 percent (three people) were in remission. This was essentially matched by the control group, who after six months with inactive devices had 17 percent hitting the improvement target and 7 percent in remission.
While discouraging, these numbers did not automatically sink the trial. Rather, this interim analysis was done to gauge the trial’s likelihood of hitting its outcome goals if it implanted 200 patients for at least half a year. But if the calculated likelihood fails to clear a trial-specific, predetermined minimum set by the FDA—a sort of kill switch—the FDA will usually end the trial with a so-called “halt for futility.”
For the Broaden trial, the FDA had set this bar at a likelihood of success of one in 10. The futility analysis calculated its likelihood of success as one in six. Modest odds, to be sure, but it easily cleared the FDA bar. The trial could continue.
A trial sponsor can stop a trial at its own prerogative. St. Jude now did so. Sometime in 2013, the company informed the Broaden team—Mayberg and dozens of cooperating researchers at the 15 research centers—that it was stopping the trial. St. Jude never said why. DBS procedures can cost upward of $100,000 a patient, so continuing would have been expensive for St. Jude. Perhaps they had their own kill point somewhere north of one in six. In any case, they stopped the trial.
St. Jude and then Abbott, a larger company that later bought St. Jude, would continue to pay for the care of the implanted patients who wanted to either continue or have their devices removed. They’d pay the research centers to continue to collect data until every patient had hit the two-year mark. But they would implant no more patients, and they would cease their attempt to get FDA approval. Five years in, roughly $10 million out, and a decade after Mayberg implanted her first horribly sick patient, the trial was over.
The first reaction to this halt—to the end of this keenly anticipated test of a depression treatment hailed as the most original and promising in decades—was crickets. St. Jude said nada. The researchers, who’d agreed not to talk until the data was published, zipped it. No one associated with the study publicly marked its halt.
Yet word slowly slipped out.
The first leak came via James Cavuoto, an industry analyst who in late December 2013 reported in his newsletter, Neurotech Business Report, that he had learned at a scientific meeting that the Broaden trial had “failed a futility analysis.” This news, Cavuoto wrote, “cast a pall over an otherwise upbeat attendance ... 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.”