Boston Scientific Stent Study Questioned by Wall Street JournalAug 14, 2008 | Parker Waichman LLP
The Wall Street Journal is reporting that a study used by Boston Scientific in its quest to garner U.S. approval for its Taxus Liberte stent used a flawed equation that favored the device. According to the Journal, had Boston Scientific used one of several other methods of calculation, the Liberte clinical trial would have been a failure.
Stents are tiny wire-mesh tubes used to prop open arteries after doctors clear them of blockages. The Taxus Liberte Stent is already approved overseas, and it is one of Boston Scientific's best selling stents abroad. The company's Taxus Express is the top seller in the U.S. In considering approval of the Liberte, the Food & drug Administration (FDA) asked the company to show that its anticlogging performance in patients was "non-inferior" to the Taxus Express. Boston Scientific claims that the Atlas study, published in 2006, did just that.
But according to The Wall Street Journal, those claims don't really add up. To reach its conclusion, Boston Scientific used the Wald interval, which has long been criticized by statisticians for exaggerating the certainty of clinical trial results. What's worse, when publishing the results of the 2006 Liberte study, Boston Scientific never bothered to disclose that it had employed the Wald interval.
The Atlas study compared Taxus Liberte to the Taxus Express. According to the findings touted by Boston Scientific, the Liberte's anticlogging performance in patients was "non-inferior" to the Taxus Express. According to The Wall Street Journal, the company said that there was less than a 5% chance that its finding was wrong - a measure known as p-value. In April 2007, in the Journal of the American College of Cardiology, the company's researchers for the first time specified the p-value: 4.87%. Scientists generally regard studies with p-values above 5% to be failures, and medical journals typically won't publish them.
But the Journal did its own analysis of the Liberte study using equations other than the Wald interval and found that study's p-value was about 5.1% -- failing to rule out the possibility that patients getting the Liberte stent will have markedly more artery recloggings than those receiving the Express.
The Journal also sited other problems with the Taxus Liberte study. For one thing, because the Liberte stent uses a design similar to its predecessor, the Express, the FDA allowed the company to conduct an easier test than would be required for a newer product.
The FDA also allowed Boston Scientific to leave out a control group of patients newly implanted with the Express. Instead, Boston Scientific was allowed to compare the Liberte's fresh results with data it had collected on Express patients a few years earlier. Boston Scientific also didn't have to "blind" participants in the study. Patients and doctors were aware that the stent being implanted was the model on trial -- a Liberte. That can lead to a placebo effect, according to the Journal article.
Finally, The Wall Street Journal says Boston Scientific wasn't required to prove that the Liberte was "superior" than a previous treatment, only that it wasn't "inferior" to Express. Even then, Boston Scientific proposed-and the FDA allowed -a benchmark in which Liberte could be up to three percentage points worse than Express.
The FDA is still debating whether or not to approve the Liberte. But it ha given Boston Scientific an "approvable" letter that indicates it eventually will.