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That Forest off-label promoted Celexa for use in children prior to September 2002 is an undisputed fact. However, starting in December 2001, Forest began aggressively using the “positive” results of MD-18 to promote the use of Celexa and, later, Lexapro for use in children. Specifically, Forest wanted the data presented at a scientific conference so it could reference the presentation in various types of promotional activities including continuing medical education (“CME”) programs. On September 21, 2001, John MacPhee of Forest outlines what he wanted to accomplish with the MD-18 pediatric data: get the pediatric data from MD-18 published as soon as possible so that Forest can use the data in CME programs for marketing.
A few weeks later, on October 15, 2001, Jeffery Lawrence of Forest wrote to Mary Prescott at the medical communications company, BSMG/Weber Shandwick, asking about the status of MD-18 manuscript and explaining that “we would like to wrap some PR and CME around this data[.]” In response, Ms. Prescott explained “I don’t know that any decision has been made about who is going to write the manuscript (not to be confused with who is going to be the author[s] of the manuscript. . . . But, for reasons I’ll list below, I think it would make sense to have a first draft prepared in-house . . . or here, if Bill Heydorn’s group is swamped[.]” She went on to explain that “I’ve heard through the grapevine that not all the data look as great as the primary outcome data. For these reasons (speed and greater control) I think it makes sense to prepare a draft in-house that can then be provided to Karen Wagner (or whomever) for review and comments.” She advised that “[r]egarding PR, it will be possible to generate some PR around the presentation of the data . . . and especially if published in a top-tier journal like JAMA — Forest can expect substantial media coverage.” This prompted Mr. Lawrence to email Dr. Paul Tiseo, the researcher overseeing MD-18: “Have you heard anything else about the Pediatric data? When we last talked, you mentioned some of the measures didn’t look that great[.]”
Then, on October 31, 2001, Christina Goetjen of Forest reported back about the company’s attempt to enlist Dr. Wagner. Apparently, Dr. Wagner agreed to help and began advising Forest about the marketing advantages of the data:
We spoke with Karen Wagner today about the current state of affairs regarding the pediatric data. . . . She . . . reminded us that if we want to appeal to the PCP and Pediatric audiences, we need to publish in a place that provided the appropriate readership (something JAMA would’ve done.) She also said that the lack of data regarding the use of Celexa for pediatrics is limiting it to “last choice” among physicians – she just wanted to make sure we understood the marketing advantages of the data. I assured her we got it.
She is excited about our Pediatric Regional CME series and will be a fundamental part of speaker selection. She knows that she and Jeff will be working closely as I will be on maternity leave.
In response, Mr. MacPhee explained “my feeling is that the fact that we are last for ped use is the very reason we can’t wait to disseminate data[.]” Ms. Goetjen assured Mr. MacPhee that Dr. Wagner “is committed to our aggressive timeline as she understands the urgency to get this data in front of our audience as soon as possible if we’re going to maximize the impact.” Ultimately, they all agreed to have BSMG write the first draft: “Bill thought it would be best if BSMG wrote the first draft… Karen Wagner also realizes that we want this done quickly[.]” Forest enlisted Natasha Mitchner, an admitted ghostwriter. Notably, a week after these decisions were made, Mr. Lawarance specifically asked for an Excel file of all “the Celexa targets who are pediatricians, and or Pediatric Psychiatrists.”
In December 2001, Dr. Wagner traveled to the annual convention of the American College of Neuropsychopharmacology (ACNP) in Hawaii and presented the “positive” results of MD-18. Her presentation, which was ghost-authored by Ms. Mitchner, did not mention or discuss the negative results of 94404, it did not discuss the fact that every secondary efficacy endpoint for MD-18 was negative, and it did not disclose that MD-18’s primary efficacy measure only achieved statistical significance by including data from unblinded patients. Instead, she presented the “positive” results of the primary endpoint, stating that MD-18 was evidence that Celexa was effective in children.
With the “positive” data presented at a scientific conference, Forest immediately started using the false data to promote the efficacy of Celexa in children. For example, Forest issued a press release about Dr. Wagner’s ACNP presentation, describing the “positive” results of MD-18. Forest contracted with a company called GCI “to start working a release and any other way they can spin this data[.]” Ms. Goetjen explained that Forest wanted to issue the press release so it could “put a promotional spin on it and . . . issue additional PR when it is published[.]”
In the release, Dr. Wagner is quoted: “This study is significant because few studies involving any antidepressant have shown efficacy compared to placebo in the treatment of depression in children . . . Citalopram is now one of the few therapies for which we have data showing safety and efficacy for this population.” The press release made no mention of Study 94404, MD-18’s negative secondary endpoints, or the unblinding issue, i.e., it had Forest’s “promotional spin” on it.
Forest then paid Dr. Wagner to travel around the country and tell physicians, in meetings and formal CME programs, that Celexa was effective in children based on the results of MD-18. Forest sponsored a CME program which was hosted and presented by Dr. Wagner, where she cited and discussed the “positive” data from the ACNP presentation to support the message that Celexa was safe and effective in children. Forest sales representatives were specifically instructed to invite physicians to the CME program—a program for which she played a major role in selecting speakers. And, like her ACNP presentation, her CME presentation did not disclose Study 94404, the negative secondary endpoints for MD-18, or the unblinding issue. Instead, the presentation ended with a multiple choice question: “Which of the following medications has been shown to be more effective than placebo in the treatment of depression in children and adolescents?” The only available correct answer: Celexa. This marketing was successful, as illustrated in Forest’s marketing plan, showing pediatric prescriptions rose after the “Wagner data” was promoted.
In 2004, the MD-18 data was officially published. However, in the years leading up to its publication, Forest tightly managed how the data was presented. For example, in an email discussing the company’s publication approach, Dr. Heydorn proposed using a “brief report” because “[a]s a Brief Report, we feel we can avoid mentioning the lack of statistically significant positive effects at week 8 or study termination for secondary endpoints.” And then again, in September 2002, the original draft manuscript mentioned a lack of efficacy in children under 12, but Dr. Heydorn instructed Ms. Prescott to “remove/revise the statement about the lack of efficacy in children [sic], since the results on that point have been pulled out.”
When the manuscript finally was published in 2004, it stated that Dr. Wagner was the primary author and did not disclose the ghostwriters. And then, years later, after the criminal plea by Forest related to this conduct became public, the journal issued a statement about the Wagner publication, stating that the authors did not properly disclose the fact that commercial writers were used. In the note, it states that Dr. Wagner claimed she was “not aware that Dr. Heydorn was working with a commercial writer.” This was false. There are multiple instances of Dr. Wagner communicating directly with the ghostwriters. Indeed, Dr. Heydorn confirmed during his deposition that Dr. Wagner was aware the manuscript was written by ghostwriters.
To this very day, Forest and Dr. Wagner still cite to and rely on MD-18 as evidence of Celexa’s efficacy, even though it only achieved a positive outcome by inappropriately including data from unblinded patients. And, Forest was only able to achieve that result by misdirecting the FDA and misleading the USAO. Indeed, prescribing guidelines for pediatric psychiatry still provide misleading and false information on Celexa in the treatment of pediatric depression based on Forest-sponsored publications.
Importantly, the USAO only criminally prosecuted Forest for off-label promotion for Celexa between 1998 and 2002, and settled civil claims for Celexa and Lexapro through 2005. It turns out, however, that this conduct continued until, at least, 2009. Gerard J. Azzari was the National Director of Sales at Forest between 1997 and 2005 and Senior Vice President of Sales between 2005 and 2010. Between 1997 and 2010, he oversaw and directed a substantial portion of Forest’s sales force, i.e., the Forest sales representatives who promoted Celexa and Lexapro to physicians. During his deposition, Plaintiffs asked Mr. Azzari whether it was true that Celexa was promoted off-label between 1998 and 2002, and he admitted it was. Then, he admitted that this misconduct continued with Celexa and Lexapro through 2009:
- So I am going to ask you again, based on your knowledge and experience between 2002 and 2009, did Forest sales representatives engage in off-label promotion of Lexapro for use in pediatric patients?
- Could I talk to counsel about this question?
- Not while it’s pending. I’m asking you for your answer based on your knowledge and experience. . . . Let me state it again, because I want you to understand what I am asking you.
- OK, yes, yes, yes.
- Based on your knowledge and experience and your years at Forest, between 2002 and 2009, did Forest sales representatives engage in off-label promotion of Lexapro for use in pediatric patients?
- I have knowledge that representatives may have presented Celexa or Lexapro inappropriately.
- Between 2002 and 2009?
- And you know that, you have knowledge of that related to Lexapro, correct?
- And that’s based on your knowledge that child specialists were on Lexapro call panels between 2002 and 2009, correct?
- No. My commentary was that individuals may have inappropriately presented Celexa or Lexapro to physicians.
Part I | Part II | Part III | Part IV | Part V | Part VI