Consumer Group Public Citizen Allegation In Medical Journal The Lancet
In an early October 2005 edition of The Lancet, a British medical journal, a published letter by the American consumer group Public Citizen accused GlaxoSmithKline ("Glaxo") of misleading the FDA as regards company's asthma drug Serevent. In particular, Public Citizen alleges that Glaxo manipulated data from the Salmeterol Multicenter Asthma Research Trial in order to make Serevent appear to the FDA that it was safer than the true trial data demonstrated.
The Public Citizen allegations of misconduct by Glaxo concern the Salmeterol Multicenter Asthma Research Trial, or SMART trial, which was a large 28-week trial involving tens of thousands of patients. The SMART trial was initiated in 1996 to address emerging safety issues concerning Serevent, a long-acting beta agonist ("LABA") used to help patients during an asthma attack. Public Citizen alleges that when Glaxo submitted its final SMART trial results to the FDA in April 2003, the drug company included data from six months after the trial ended, thereby skewing the results.
In relevant part, during the 28-week SMART trial 13 patients taking Serevent suffered asthma-related deaths compared to the three asthma-related deaths involving patients taking the placebo in the SMART trial. Accordingly, patients taking Serevent had four times as many deaths.
But six months after the SMART trial ended, the numbers had changed such that the death factor was reduced to just 2.5: patients in the Serevent group had suffered 15 deaths, while the placebo group had six asthma-related deaths.
Possible manipulation of the SMART trail data by Glaxo came to light when documents about Serevent were made public prior to an FDA Pulmonary-Allergy Drugs Advisory Committee meeting in July 2005.
It has been reported that some documents available on the FDA's web site indicate, at least, an FDA staff-level concern about the SMART trial data that was initially submitted by Glaxo. "The [FDA] Division disagrees with the inclusion of the post-study adverse event data in the analysis," one FDA review summary reportedly states.
According to Public Citizen, Salmeterol was dispensed in the U.S. more than 2.1 million times in 2004, and the combination product, Advair, was dispensed more than 16.1 million times in 2004. Public Citizen listed Serevent as a “Do Not Use” drug in its Worst Pills, Best Pills newsletter in March 2003.
At present, Serevent, or salmeterol -- which asthma medication is known as Advair when it is combined with the steroid fluticasone -- carries a "black-box" warning about a small but significant increase in asthma-related deaths among patients who use Serevent.
(Posted by: Tom Lamb)