by CBS News Investigative Producer Laura Strickler.A sealed court deposition in a civil lawsuit against Glaxo Smith Kline obtained by CBS News sheds light on the fight that raged inside the FDA between those who wanted to pull the drug and those who wanted to keep the drug on the market.
The deposition describes an internal email written by the Chief Medical Officer for Glaxo Smith Kline in which he tells his colleagues an FDA official divulged details of an internal debate within the regulatory agency over whether or not to add a sharper label to the drug in 2007.
In the deposition, former FDA safety reviewer Dr. Rosemary Johann-Liang was asked about the "personal decorum" of an FDA official sharing details about an internal debate with a pharmaceutical executive. Johann-Liang said this kind of communication should not happen. She said: "I believe there are certain--certain decorums one must abide by when one is regulating an application and deciding upon labeling...".
An FDA spokesperson would not comment on the matter citing ongoing litigation.
Johann-Liang says upon first review of "preclinical data" of glitazones, the class of drug that includes Avandia, she saw "fluid retention of the body that's seen throughout. It's a recurrent story," she said. She described that this can cause "fluid collection like around your ankles and legs..."
Dr. Johann-Liang revealed in 2007 that when she pushed for a new severe warning on Avandia she was reprimanded by her superiors.
Dr. Mary Money of Hagerstown Maryland told CBS News she called the FDA to raise concerns about fluid retention in her patients that were taking Avandia as far back as March 2000. She described one patient's legs as being as swollen as "stove pipes" after taking the drug. Money says the only response she ever received from the FDA was a form letter that was viewed by CBS News.
An October 7, 2008 internal FDA Avandia review from the Office of Surveillance and Epidemiology released by Senate investigators read: "We conclude that the cardiovascular risks associated with rosiglitazone are excessive...Rosiglitazone should be pulled from the market." The agency did not act on this review.
The reviewers also included a lengthy analysis of whether or not it was ethical for the FDA to ask a company to run clinical trials testing the safety of a drug if there were concerns that it could cause heart failure. A 2007 study showed Avandia led to a 43 percent increase in risk of heart attack.
The report is referring to a large clinical trial the company began in spring of 2009 involving the recruitment of 16,000 patients across the globe including patients in places such as Pakistan, Colombia, Latvia and Slovakia as well as in the United States.
The authors wrote that the patients participating in the study could be harmed and would not benefit from the trial, "but the organization [Glaxo Smith Kline] sponsoring the trial could very well benefit."
The authors concluded that continuing the trial would be "unethical and exploitative." The clinical trial is ongoing.
CBS News reported earlier that thewithin the last week.
Senator Charles Grassley, (R-IA) ranking member of the Senate Finance Committee who oversees the FDA has pointed to the Avandia controversy as a call for reform, "The inequality between the FDA's post-market office and the FDA office that decides whether to approve a drug for market in the first place has led to FDA physicians and scientists who are committed to the post-market monitoring of drugs being suppressed or even ignored," he said.
Glaxo Smith Kline representatives defended their drug at the FDA meeting and released a statement: "Since 2007 we have seen results from six controlled clinical trials looking at the cardiovascular safety of Avandia and together they show that this medicine does not increase the overall risk of heart attack, stroke or death."
The company also released a separate statement in response to the documents released by the Senate Finance Committee, "The documents do not offer new clinically relevant scientific information, and do not provide the full extent of GSK's studies and evaluation of Avandia." The company said that Senate investigators were cherrypicking documents from the million of files turned over in the lawsuit.