"Given your history, with this application and this general issue," Dr Katz told Dr Mosholder, "we think you would be the right person to help us think about the best way to approach the data in the other NDAs (and their sponsors), as well as to provide ideas for further sources of potentially relevant data and possible approaches to better evaluate this signal study (e.g., insurance claims databases, etc.)."
"Also, we'd like you to be in on the phone call, if possible," he said.
In responding to the email, Dr Mosholder told Dr Katz: "As I recall, a number of the other SSRI pediatric supplements showed signals for behavioral adverse events. But these were mainly events such as agitation and hypomania, not self-injury (unless, as you suggest, they were similarly obscured by inappropriate terminology)."
A February 4, 2004, email from another highly paid Glaxo academic, Dr Neal Ryan, to fellow Study 329 authors, Dr Karen Wagner and Dr Keller, illustrates their alarm over the FDA's order for drug companies to reevalute all SSRI studies. The email states:
FDA made each company go line by line through absolutely all documentation of all kids in all their studies. This is where 4 more subjects in our joint study fell out, unfortunately all the Paxil group. Don't know severity or more information about this yet.
In a curious Glaxo email titled, "Study 329 Update," to Dr Ryan, Dr Wagner and Dr Keller, the investigators who supposedly reviewed the data and authored the report, a GSK employee wrote:
We want to update you, as investigators on Study 329, about additional potential pediatric suicidality cases that were recently discovered. In a manual review of all SAE narratives and "trauma" cases, 10 additional events potentially suggestive of intentional self injury, suicidal ideation, or suicide attempt were identified. Four of the 10 events occurred in study 329, all in the paroxetine group. Consequently, this could potentially change the number of paroxetine suicide-related adverse events for that study from 6 to 10.
"These cases," the email states, "included among those undergoing blinded review by Dr. Wagner, Dr. Ryan, and Dr. Apter for the pediatric suicidality manuscript."
This message apparently caused Dr Ryan to panic because he was being contacted by reporters. In an email response he stated:
With your email yesterday (appended below) about 4 additional "events" in Study 329 on the Paxil arm, those of us involved in writing the recent letter to the reporter asking about details of our article need very very quickly to get absolutely as much information as you have and understand what part of this we need to pass on to her. Otherwise we are in the challenging position of sending her a good-faith effort at directly answering her questions that we find very shortly thereafter is no longer the most complete information available to us and which therefore might appear misleading.
"Can we get a much fuller explanation in email?" Dr Ryan asks. "Should we quickly set up a conference phone call?"
After viewing the Panorama program, Dr Fiona Godlee, Editor of the British Medical Journal, wrote an article stating: "Panorama's account of GlaxoSmithKline's successful attempts to market Seroxat for use in children, despite the fact that its own published trial found evidence of serious adverse effects and failed to show benefit, is fascinating but depressingly familiar."
"What is even more depressing," she notes, "is that such behaviour is still so widely tolerated within medicine."
"What is clearly wrong," Dr Godlee writes, "is writers, academics, or clinicians concealing under their coat tails an army of company spin doctors intent on distorting the scientific record."
As for what can be done to change what she refers to as "the blind-eye culture of medicine," Dr Godlee states: "In the interests of patients and professional integrity I suggest intolerance and exposure."
"And if journals discover authors who are guests on their own papers," she says, "they should report them to their institution, admonish them in the journal and probably retract the paper."
