An inappropriate analysis of clinical trial data by Glaxo researchers obscured suicide risks associated with Paxil for 15 years, writesThe New Scientist, citing court documents that were recently unsealed in by a federal court in California. ( Take a look).
Two years ago, Glaxo alerted the public to an increased risk of suicide associated with its pill. However, an analysis of internal Glaxo memos and reports suggests the drugmaker had data demonstrating an eightfold increase in suicide risk as early as 1989.
Harvard University psychiatrist Joseph Glenmullen, who studied the papers, tells the mag it was “virtually impossible” Glaxo misunderstood the data. The drugmaker calls that "absolutely false." He reached his conclusion after reviewing documents obtained by lawyers who have filed about 30 cases against Glaxo over Paxil and suicides or suicide attempts.
The analysis focuses on the so-called washout phase preceding a trial, when subjects stop taking most or all meds to avoid confusion with results from the trial itself. Because the washout occurs before patients randomly receive either the drug or a placebo, side effects can't be attributed to the trial and so are seldom, if ever included in final results, New Scientist notes.
UPDATE: Chuck Grassley of the Senate Finance Committee has just written Glaxo seeking nine pages that weren't made available with the unsealed documents. Here is the letter.
However, Glaxo researchers submitted data to the FDA in the late 1980s and early 1990s that included suicides and suicide attempts from the washout period in the results for the placebo arms, or portions of the trials, but not from the Paxil arms. Glenmullen alleges these extra “placebo” suicides negated suicides attributed to Paxil, making the pill appear safer. He argues that if the washout results had been excluded, the data would have shown Paxil posted an eightfold increase in the risk of suicidal behavior in adults.
Glaxo spokeswoman Mary Anne Rhyne tells the mag that including washout data "was intended to present the full picture of events that occurred in all phases of the clinical trials, starting from the time patients were enrolled, before they were randomized." She adds that even without the washout data, paxil still came out as safe as the placebo in the trial. And she accused Glenmullen of incorrectly analyzing the data to reach the opposite conclusion, but she ddidn’t respond the the mag's request for numerical proof that his conclusion was incorrect.
For his part, Glenmullen suggests the FDA would have acted differently had the washout data been used more explicitly. Rhyne says that documents still under court seal show the FDA to be fully aware of how the washout data was being used. But Glenmullen quotes Martin Becher, the FDA staffer who reviewed Paxil safety data, as agreeing during a pre-trial hearing that the use of washout data was "scientifically illegitimate."