July 19, 1999 —Jim McCafferty,SKB Executive,sends Sally Laden a memo with suggestions for edits. The two "minor" ones are (1) the article should not imply that most of the trial subjects have a family history and a diagnosis of major depression when they do not, and (2) the statement that there are unlikely to be any more tricyclic antidepressant trials because of expired patents, while true, is too direct and sounds too commercial. The third, "major" issue he raises is safety. He writes:
"It seems incongruous that we state that paroxetine is safe and yet report so many SAEs*. I know the investigators have not raised an issue, but I fear the Editors will. I am still not sure how to describe these events…"
*serious adverse events
August, 1999 —Martin Keller submits the article (see deposition transcript page 370) "Efficacy of Paroxetine in the Treatment of Adolescent Major Depression, A Randomized Controlled Trial" to the Journal of the American Medical Association (JAMA) as the preferred publication vehicle because this journal reaches primary care doctors and paediatricians as well as psychiatrists.
August, 1999 —The FDA releases its final Guidance for Industry: Consumer-Directed Broadcast Advertisements.
Direct-to-Consumer (DTC) advertising has given a major boost to drug sales. In a 2002 article, "Paxil is Forever", Minneapolis City Pages quoted:
"DTC is a great way to create demand," the trade journal Drug Topics quoted one marketing VP as saying. "Advertisers are trying to help consumers recognize a specific symptom and then recognize that something can be done to alleviate the symptom." The same article noted that: "During the first half of (2002), (Paxil's) sales were up 18 percent in the United States. Every day an estimated 3,000 to 5,000 Americans begin taking Paxil."
October 22, 1989 — Three peer reviewers at JAMA flag concerns about whether the study really shows that paroxetine is effective and JAMA declines to publish the study. The peer reviewers "pointed to the low HAM-D cut-off, the [confounding] effect of supportive care, the high Placebo response, the small or absent differences in rating scales, the significant incidence of Serious Side Effects with Paroxetine, and the inappropriately [escalating and high] dosing with Imipramine".
The rejection letter states that "this rejection is no reflection on the scientific quality of your manuscript…", and "The 11 journals published by the AMA constitute an editorial consortium to give each submitted manuscript more than one option for publication. This consortium includes The Archives of General Psychiatry, to which we would be happy to forward your paper, should you so wish.
Obviously, your paper will not be guaranteed publication mainly on the strength of being referred by us. However, we would be glad to forward all copies of your manuscript to the editor for evaluation, along with the reviews (copies enclosed for your information). Further disposition would then be decided by the specialty journal editor."
December 7, 1999 —Letter: Sally Laden writes to Jim McCafferty of SKB:
"Dr Keller submitted the manuscript to JAMA in early August, 1999. The journal elected not to publish the paper and notified Dr Keller in November. In a conference call in November involving Drs Keller, Ryan, and Strober and Jim McCafferty, the action plan itemized below was agreed upon:
Resubmitting this manuscript is our top priority, and we will be asking for rapid review when we send materials to the authors…"
Note that, at this point, the plan is to submit the revised manuscript to the American Journal of Psychiatry.