FDA Approves Boston Scientific Stent Despite Earlier ProblemsOct 13, 2008 | Parker Waichman LLP
Late last week, Boston Scientific Corporation announced that U.S. health regulators approved the next-generation version of its widely used Taxus drug-coated stent. Boston Scientifc plans to begin selling the stent in early November.
Meanwhile, in March, Boston Scientific received an approvable letter from the Food and Drug Administration (FDA) for the stent, the Taxus Liberte. Receiving an approvable letter indicates that certain conditions must be met before full FDA approval is granted. The company also received a corporate warning letter from the FDA in 2006.
Stents are tiny wire-mesh tubes used to prop open arteries after doctors clear them of blockages. Newer stents are drug-coated to help prevent blood vessels from reclogging. The Taxus Liberte Stent is already approved overseas, and is one of Boston Scientific’s best selling stents abroad; the Taxus Express is the top seller in the U.S. In considering approval of the Liberte, the FDA asked Boston Scientific to prove its anti-clogging performance in patients was “non-inferior” to the Taxus Express. Boston Scientific said structural design improvements over the original market-leading Taxus make the Liberte more flexible for easier insertion during angioplasty procedures.
Meanwhile, this summer, the Wall Street Journal reported that a study used by Boston Scientific, when pursuing U.S. approval for its Taxus Liberte stent, used a flawed equation favoring its stent. According to the Journal, had Boston Scientific used one of several other calculation methods, the Liberte clinical trial would have failed. According to the Journal, Boston Scientific used the Wald interval, long criticized by statisticians for exaggerating clinical trial results. Worse, when publishing results of the 2006 Liberte study, Boston Scientific neglected to disclose it 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 anti-clogging performance in patients was “non-inferior” to the Taxus Express. According to the Journal, Boston Scientific said there was less than a five percent 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 percent. Scientists generally regard studies with p-values above five percent to be failures, and medical journals typically will not publish such results.
The Journal’s own analysis of the Liberte study using equations other than the Wald interval 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 example, 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 and allowed Boston Scientific to omit 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 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.