UNITED STATES DISTRICT COURT
FOR THE DISTRICT OF MASSACHUSETTS

 

UNITED STATES ex rel. GREG
THORPE, ET AL. [Consolidated]
Plaintiffs,
v.
GLAXOSMITHKLIN PLC, and
GLAXOSMITHKLIN LLC,
Defendants

CA. No. 

FILED UNDER SEAL



 

UNITED COMPLAINT

l. The United States brings this action to recover treble damages and civil penalties
under the False Claims Act, damages and other monetary relief under common law and equity
against the defendants GlaxoSmithKline and GlaxoSmithKline LLC (together for
causing the submission of false or fraudulent claims to federal health care programs.

2. From 1999 through 2010 in some instances, GSK engaged in a fraudulent scheme
to deceive and defraud physicians, patients, regulators, and federal health care programs to cause
prescribing and payment for certain of drugs. This conduct includes repeatedly publishing
and promoting false and misleading accounts of studies and treatment guidelines to convince
physicians to use GSK drugs. GSK misrepresented clinical evidence, downplayed or ignored
safety risks, and failed to disclose the rejection by the United States Food and Drug
Administration of some of the exact claims GSK was making to physicians. GSK
promoted these products for uses that the FDA had not approved as safe and effective (?off?label?
or ?unapproved? uses), and for uses that were not medically accepted indications covered by
federal health care programs. GSK also used a wide variety of gifts, payments and other forms
of remuneration to induce physicians to prescribe drugs, including trips to Bermuda and

Jamaica, spa treatments and hunting trips, and sham consulting fees.





(C)



4.

fraudulent promotion of its drugs included the following:

Promoting Paxil, an antidepressant drug, as safe and effective for children and
adolescents, despite the lack of FDA approval for this use and three GSK clinical
trials that failed to demonstrate Paxil?s effectiveness while raising concerns
regarding an increased risk of suicide among such patients.

Promoting Wellbutrin SR an antidepressant drug, for unapproved uses
including for children and adolescents, to treat Attention De?cit Disorder
Attention De?cit and Hyperactivity Disorder bipolar
disorder, weight loss, obesity, sexual dys?inction, anxiety, and as an ?add?on?
therapy to other antidepressants, despite the fact that the drug was not
demonstrated to be safe and effective for any of these uses.

Promoting Advair, a combination of asthma drugs, for ?rst?line use in mild asthma
patients whose asthma could be controlled on one component alone?contrary to
the FDA-approved label, speci?c FDA guidance, and established asthma treatment
guidelines. In falsely claiming that Advair was superior to each of its components
for this use, GSK relied on a study the FDA had specifically evaluated and rejected
as showing superiority in application for an indication for this use.

Promoting certain GSK drugs listed below with various forms of illegal
remuneration, including cash payments disguised as consulting fees, expensive
meals, weekend boondoggles, and lavish entertainment to prescribers and other
health care professionals to induce them to prescribe and recommend 
drugs, including those paid for by federal health care programs, all in violation of
the federal anti-kickback statute. 42 U.S.C. l320a?7b.

conduct, including its false and fraudulent statements, illegal promotion

and payment of illegal inducements to prescribers, caused false or fraudulent claims to be

submitted to federal health care programs for drugs, including claims for Advair, Paxil and

WBSR, for uses that were not eligible for payment and for physician services relating to the

prescribing of those drugs.

5.

I. THE PARTIES

The United States brings this action on behalf of the federal health care programs

the Department of Health and Human Services and the Centers for Medicare 

Medicaid Services which administers the Medicare and Medicaid programs.

6.

This is the United States? Complaint as to the claims as to which it has intervened

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in Civil Action Nos. ll~10741?NG, (D. Mass),
which were ?led by various relators and are consolidated as CA. No. 11-10398-NG.

7. Defendant GlaxoSmithKline is a public limited company, incorporated under
English law, with headquarters in Brentford, England. Glaxo SmithKline was formed in 2000
by the merger of GlaxoWellcome and SmithKline Beecham plc. It has operational
headquarters in Research Triangle Park, North Carolina, and in Philadelphia, 

8. Defendant GlaxoSmithKline LLC, a Delaware limited liability company, is the
United States subsidiary of GlaxoSmithKline plc. GlaxoSmithKline LLC is the successor of
SmithKline Beecham Corporation, which was the successor of SmithKline Beckman
Corporation. Glaxo SmithKline LLC has headquarters in Philadelphia, and
Research Triangle Park, North Carolina.

II. JURISDICTION AND VENUE

9. This Court has subject matter jurisdiction under 28 U.S.C. 1331 and 1345.
The Court may exercise personal jurisdiction over GSK pursuant to 31 U.S.C. 3732(a) and
because GSK transacts business in the District of Massachusetts.

10. Venue is proper in the District of Massachusetts under 31 U.S.C. 3732 and 28
U.S.C. 1391(b) and (0) because GSK has transacted business in this District.

OFF-LABEL MARKETING OF PAXIL

11. Paxil (paroxetine) is an antidepressant approved by the FDA for adults with major
depressive disorder or ??depression?), and other mental diseases.

12. The FDA has never approved Paxil to treat depression in children or adolescents
under the age of 18. Nevertheless, from 1999 through at least 2003, GSK promoted Paxil for use
in this population, While concealing the fact that Paxil failed to Show ef?cacy on any of the

primary endpoints in three controlled trials funded by GSK to study Paxil for this population. To

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drive these promotional efforts, GSK touted a medical journal article that it paid to have drafted
and that exaggerated Paxil?s ef?cacy while downplaying risks identi?ed during one of the trials.

13. The risks identi?ed in trials, once uncovered, led the FDA to require in
2004 that GSK and other manufacturers of a class of drugs known as ?selective serotonin
reuptake inhibitors? place a ?black box? warning on the labels of these products to
warn doctors about the potential suicidality risks to children and adolescents. A black box
warning is the strongest type of warning the FDA can require in a product label.

14. By misstating and exaggerating Paxil?s ef?cacy and downplaying and concealing
its risks during sales calls and promotional events, GSK misled the medical community about the
risks and bene?ts of Paxil use in patients under 18 and caused false and medically inappropriate
claims for Paxil prescriptions to be submitted to federal health care programs.

A. Three GSK Clinical Trials Failed To Demonstrate Paxil?s Effectiveness In Treating
Depressed Children

 

15. Between 1994 and 2001, GSK conducted three clinical trials of Paxil?s safety and
ef?cacy in treating depression in persons under 18. In all three studies, Paxil failed to reach
statistical signi?cance on the primary and secondary ef?cacy measures (or endpoints) in the
study protocols. Due to these negative results, internally described as ?disappointing? and
?equivocal,? GSK never sought FDA approval of Paxil for childhood or adolescent depression.
As described below, GSK published false and misleading reports of these results,
misrepresenting positive results while down?playing signi?cant safety risks, including an
increased risk of suicide in child and adolescent patients. I

1. Study 329 Failed to Show Ef?cacy of P21in for Children or Adolescents.

16. The centerpiece of efforts to market Paxil for childhood depression was

the GSK funded Study 329, which ran from April 1994 to February 1998. This was a double-

blind, placebo?controlled study of the ef?cacy of Paxil in depressed children.

17. Study 329?s clinical trial protocol contained two ?primary? ef?cacy measures and
?ve ?secondary? ef?cacy measures. A ?protocol? is a document created prior to commencement
of the trial that describes the objectives, design, methodology, and statistical plan for the clinical
trial. Pre?speci?ed protocols are required by the FDA and scienti?c community to prevent post-
hoc selection of favorable data and endpointswie. ?cherry-picking.? A primary ef?cacy
endpoint is a speci?c event or outcome that the clinical trial is designed to assess?such as
whether a drug is more effective than a placebo in treating a condition. A ?secondary? endpoint
is typically related to the primary endpoint and may be of interest, but is not one the study is
independently statistically-powered to assess.

18. The ?rst primary endpoint in Study 329 was the degree to which a patient?s
Hamilton Rating Scale for Depression total score changed from a baseline. The
is a questionnaire to rate the severity of a patient?s depression. The other primary
endpoint: the patients? ?response? to medication, as de?ned as a 50% or greater reduction in
the patient?s score, or a HAM-D score of less than or equal to 8.

19. Study 329 did not show that PaXil was more effeCtive than a placebo on either of
its primary endpoints or any of its prede?ned secondary endpoints.

20. The 329 Study investigators later added several additional ef?cacy measures not
speci?ed in the protocol. Paxil separated statistically from placebo on certain of these measures.

2. Studies 377 and 701 Also Failed to Show Paxil Works in Patients Under 18.

21. In addition to Study 329, GSK conducted two other double-blind, placebo"
controlled studies of Paxil for pediatric and adolescent depression: Study 377 from April 1995 to
May 1998 and Study 701 from March 2000 to January 2001.

22. Like Study 329, both studies failed to demonstrate any statistically signi?cant

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difference in ef?cacy between Paxil and the placebo on any pro?Speci?ed primary or secondary
endpoint. GSK noted in an internal report on Study 377, ?the results failed to show any
superiority for Paxil over placebo in the treatment of adolescent depression.?

23. Internally, GSK acknowledged that its studies failed to provide suf?cient support
for the FDA to approve Paxil for childhood depression. In August 1998, six months after Study
329 closed, GSK noted in a Management Summary that:

In both 329 (US) and 377 (EU) unable to detect a clinically or statistically

signi?cant difference between treatment groups in the prospectively de?ned

primary variable therefore no submission for label indication for

use of [Paxil] in Adolescent Depression.

24. Similarly in October 1998, GSK noted in a discussion of Studies 329 and 377:

As you w[e]ll know, the results of the [329 and 377] studies were disappointing in i

that we did not reach statistical signi?cance on the primary end points and thus the

data do not support a label claim for the treatment of Adolescent Depression. The

possibility of obtaining a safety statement from this data was considered but

rej ected.? The best which could have been achieved was a statement that, although

safety data was reassuring, ef?cacy had not been demonstrated. Consultation of

the Marketing Teams via Regulatory con?rmed that this would be unacceptable

commercially and the decision to take no regulatory action was recently

endorsed[.]
GSK concluded: ?it would be commercially unacceptable to include a statement that ef?cacy had
not been demonstrated, as this would undermine the pro?le of [Paxil].? Exhibit l.

25. As for Study 701, GSK noted in its ?nal clinical report on that study that ?[t]he

results of this study failed to provide evidence for the primary and secondary endpoints that

[Paxil] is more ef?cacious than placebo in treating children and adolescents with 

B. GSK Published an Article That Misstated Paxil?s Ef?cacy and Safety for Children and
Adolescents

26. In April 1998, GSK hired Scienti?c Therapeutics Information, Inc. (STI) to
prepare a journal article about Study 329. GSK worked closely with STI on the article by

providing a draft clinical report to ?serve as a template for the proposed publication,?

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commenting on multiple drafts, and approving the ?nal version.

1. In Publishing Study 329, GSKFalsely Claimed that It Demonstrated Paxil?s
Ef?cacy in Treating Depression in Patients Under 18. 

27. The abstract of the article sent to AMA stated that Paxil was ?a safe and effective
treatment for major depression in adolescents.? The article, however, did not expressly identify
the two protocol-speci?ed primary ef?cacy measurem?or that Paxil failed to show superiority to
placebo on those two measures. Instead, the article claimed that there were eight ef?cacy
measures and Paxil was statistically superior to placebo on four of them.

28. AMA rejected the article in December 1999? and provided comments to the
article?s lead author, which he then circulated to GSK and STI. Some of the comments were
extremely critical of how the article portrayed the study?s results. One comment provided:

[t]he major ?nding of this study was the high placebo response rate, nearly 50%.

Paroxetine produced only a 20% higher response rate than placebo and then on

some but not all of the scales Readers of this paper might receive the

wrong impression and believe that a 65 to 70% response rate could be achieved
with paroxetine without the education and supportive that the
placebo-treated patients in this study received. The outcome is particularly
worrisome in this age of health cost containment. Thus, this study could do more
harm than good unless the authors devote much more attention in their discussion

to the fact that the bulk of the effect in this study was the result of good clinical

management and not the medication.

Another noted that the E?description of ?numerically superior? is not appropriate and results
should be described as superior only when signi?cant. . .. There is a bias in reporting [Paxil]
results as numerically superior but failing to emphasize this is also the case for many of the
outcome measures with imipramine.?

29. Given the comments received, GSK and the lead author decided to revise the
article and send it to what they called ?a less demanding journal.? GSK then worked closely

with STI to revise and resubmit the article.

30. In June 2000, a revised version of the article was submitted to the Journal of the

American Academy of Child and Adolescent (J AACAP). In July 2000, JAACAP
returned the article. Like I AMA, JAACAP questioned whether the article accurately
characterized Study 329?s results on Paxil?s ef?cacy. For example, one comment stated:

Overall, this is an important study due to its large size and its design of SSRI vs.

TCA vs. Placebo. However, the results do not clearly demonstrate ef?cacy for

[Paxil]. Therefore, the authors need to clearly note [E]f?cacy was not

demonstrated for [Paxil]. It should be clearly noted that [Paxil] was not found to

be superior to placebo on [three of the seven] completed measures of

antidepressant ef?cacy in the Results subsection.

31. Another commenter noted the article obscured the primary endpoint results.

The authors should clearly note that [three of the seven] outcome measures did not

show [PaXil] was superior to placebo[.] Therefore the authors should not overstate

the ef?cacy of [Paxil]. The fact that there was not a single a priori primary

outcome measure is quite unusual for an industry sponsored study. If this is the

case, this should be clearly noted as a methodological shortcoming. If there was a

?primary? outcome measure, the authors should clearly note what that was.

32. GSK worked closely with STI to address the reviewers? comments and the article
was resubmitted to JAACAP. JAACAP ultimately accepted the article in February 2001 and
published it in July 2001. The article was titled ?Ef?cacy of Paroxetine in the Treatment of
Adolescent Maj or Depression: A Randomized, Controlled Trial.? Exh. 2.

33. The ?nal published article still mischaracterized the results of Study 329, even
with the changes. Although PaXil failed to separate statistically from placebo on both the
primary ef?cacy measures, as well as the ?ve protocol?de?ned secondary ef?cacy measures, the
article abstract ?atly stated that ?[Paxil] is generally well tolerated and effective for major
depression in adolescents? and concluded that ?[t]he ?ndings of this study provide evidence of
the ef?cacy and safety of the SSRI, [Paxil], in the treatment of adolescent depression.?

34. Although the AACAP article identi?ed the study?s two primary endpoints in the

abstract, the article did not explicitly state that Paxil failed to Show superiority to placebo on

either of the primary ef?cacy measures (the only measures that the Study 329 was speci?cally

8

designed to assess). Instead, the article falsely stated that Paxil met one of the primary
endpoints, noting how Paxil ?separated from placebo at endpoint among four of the parameters:
response primary outcome measure). . . Since one of the protocol-de?ned primary
endpoints was ?response,? the article?s statement that Paxil ?separated from placebo? on
?response,? falsely stated that Paxil had met that primary ef?cacy measure.

35. The ?nal article?s description of Paxil?s performance on the protocol?de?ned
secondary ef?cacy measures was also misleading. While the article abstract listed the five
protocol-de?ned secondary endpoints, the text of the article omitted any discussion regarding
three of the secondary measures on which Pain failed to statistically demonstrate its superiority
to placebo and instead focused on the ?ve secondary measures that GSK added belatedly and
never incorporated into the Study 329 protocol. The article claimed that these ?ve secondary
measures had been identi?ed ?a priori,? thereby incorrectly suggesting that all the secondary
endpoints discussed had been part of the original study protocol.

36. In short, the article distorted the study results and gave the false impression that
the study?s ?ndings were primarily positive, when they were, in fact, primarily negative and as
discussed below, contained a signi?cant safety signal.

2. GSK Caused the AACAP Article to Misrepresent and Minimize Paxil?s
Risks to Children and Adolescents.

37. At the same time that the AACAP article exaggerated Paxil?s ef?cacy for
treating childhood depression, it downplayed the risks that Study 329 revealed. These risks
eventually led the FDA to require all SSRI manufacturers to add a black box warning about the
heightened risks of suicidality to adolescents taking Paxil and other drugs in the class.

3 8. An earlier draft of the AACAP article (prior to the version ultimately published)

disclosed that eleven (1 1) patients who had received Paxil had experienced serious adverse

events potentially related to the drug. It stated:

Serious adverse effects occurred in 11 patients in the paroxetine group, 5 the

imipramine group, and 2 in the placebo group. An event was de?ned as serious if

it resulted in hospitalization, was associated with suicidal gestures, or was

described by the treating physician as serious. The serious adverse effects in the

paroxetine group consisted of headache during down-titration (1 patient), and

various events (10 patients): worsening depression emotional

lability g, suicidal ideation/gestures, overdoses), conduct problems or

hostility g, aggressiveness, behavioral disturbance in school) and mania

(1). Of these, worsening depression, emotional lability, headache, and hostility

were considered related or possibly related to treatment.

39. When JAMA rejected the article, one reviewer noted: is a ma} or 
omission from the tables. The serious adverse events should be at the top of any table of adverse
events and these do not favor paroxetine. In fact, it is troubling that the authors do not note a
significant increase in SAEs after paroxetine (but not IMI) relative to placebo.? That comment
was never addressed by GSK in the article. The AACAP article had a table listing adverse
events, but did not break out serious adverse events.

40. At the time GSK was circulating the draft article to AMA and JAACAP, GSK
had concerns about disclosing and publishing the increased serious adverse events associated
with PaXil, particularly due to recent events in patients taking SSRIS comniitting violent acts,
including the Columbine High School shootings.

41. GSK and STI instead revised the article to falsely state that only one of the 11
serious adverse events in Paxil patients was considered related to treatmentwand failed to
mention the fact that others had been listed by the study investigators as possibly related to
treatment. The ?nal article stated: ?Of the 11 patients [who had serious adverse events While

taking PaXil], only headache (1 patient) was considered related to paroxetine treatment.?

3. The FDA Found Paxil Was Not Proven To Be Safe and Effective To Treat
Children and Adolescents and Required Warning of the Risks.

42. In April 2002, GSK provided the FDA the results of its three pediatric depression

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studies while attempting to gain an extension on Paxil?s patent exclusivity period. In October
2002, the FDA informed GSK that the depression studies failed to demonstrate Paxil?s ef?cacy
in treating depression in individuals under age 18.

43. Moreover, the FDA asked for additional information about patients in the studies
who had experienced adverse events and who had withdrawn from the study prematurely, as well
as why GSK used the term ?emotional lability? to describe the ?ve patients who attempted to i
commitsuicide or exhibited other self?injurious behavior. In May 2003, GSK for the ?rst time
provided the FDA with additional safety data from the studies.

44. Although GSK told the FDA there was no statistically signi?cant difference in
suicidality between placebo and Paxil in all the Paxil pediatric depression studies cumulatively,
the difference between the potential suicide-related events among Paxil patients versus potential
suicide?related events among placebo patients became statistically signi?cant when the ?rst 30
days after therapy were included in the analysis.

45. Likewise, upon closer examination the number of possible suicide?related events
among the Study 329 Paxil patients increased beyond the ?ve patients that GSK described in the
JACAAP article as having ?emotional lability.? While collecting safety information for the
FDA, GSK admitted that there were four more possible suicide?related events among Paxil
patients in Study 329. In addition, the FDA later identi?ed yet another possibly suicide-related
event in the Study 329 Paxil patients, which also was not among the 11 serious adverse events
listed in the JAACAP article. Thus, altogether, 10 of the 93 Paxil patients in Study 329
experienced a possibly suicidal event, compared to one of the 87 patients on placebo. This is a
fundamentally different picture of Paxil?s pediatric safety pro?le than the one painted by the
JAACAP article, which listed at most ?ve possibly suicidal events among Paxil patients, brushed

those off as unrelated to Paxil, and concluded that treating children with Paxil was safe.

11

46. In June 2003, the FDA announced that although it had not completed its review of
the data, it recommended that PaXil not be used to treat depression in patients under age 18.

47. In March 2004, the FDA issued a public health advisory requesting that SSRI
manufacturers, including GSK, change the labels on their drugs to include ?a [w]arning
statement that recommends close observation of adult and pediatric patients treated with these
agents for worsening depression or the emergence of suicidality.?

48. In June 2004, the British Medical Journal published an article that accused the
JAACAP article of ?biased reporting.? Regarding serious adverse events, the article said:
?[D]espite five of these patients being admitted to hospital with events known to occur with the
use of selective serotonin reuptake inhibitors, including suicidality, only one serious event
(headache) was judged by the treating investigator to be related to paroxetine treatment. The
criteria for determining causation of serious events were not stated.?

49. In October 2004, the FDA directed GSK and other antidepressant manufacturers
to include on their labels a black box warning to alert physicians about the potential for increased
risk of suicidality in children and adolescents taking these drugs. The black box warning stated
that ?[a]ntidepressants increased the risk of suicidal thinking and behavior (suicidality) in Short-
term studies in children and adolescents with Maj or Depressive Disorder (MDD) and other
disorders.? The FDA also required the labels to state:

The risk of suicidality for these drugs was identi?ed in a combined analysis of

short?term (up to 4 months) placebo-controlled trials of nine antidepressant drugs,

including the selective serotonin reuptake inhibitors (SSRIS) and others, in children

and adolescents with major depressive disorder (MDD), obsessive compulsive

disorder (OCD), or other disorders. A total of 24 trials involving over

4400 patients were included. The analysis showed a greater risk of suicidality

during the ?rst few months of treatment in those receiving antidepressants.

50. In May 2006, GSK sent letters to physicians and updated Paxil?s label to include

an advisory regarding PaXil and suicidal tendencies in children, adolescents and young adults.

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C. GSK Off?Label Marketed Paxil For Depression In Children and Adolescents

51. Despite the failure of its three clinical trials and the absence of FDA approval,
GSK actively promoted Paxil to treat adolescent and childhood depression from 1999 to at least
2003. As re?ected in internal GSK business plans, expanding PaXil?s reach into the adolescent
depression market was a key strategic goal well before the clinical trials were completed and
well after GSK learned of the disappointing results of its three depression studies.

52. Likewise, notwithstanding Paxil?s failure to meet the primary endpoints of
Studies 329 and 377, 2000?2002 PaXil operating plan was to ?[d]evelop/ grow adolescent
market by leveraging recently completed studies in adolescent depression and 

53. Similarly, in 2000, consultant prepared a 32-page report titled,
?Positioning Paxil in the adolescent depression market getting a headstart.? The purpose of the
report, prepared at request, was ?to assess the efficacy data relating to the use of Paxil for
the treatment of depression and anxiety?related disorders in adolescents and to make
recommendations on how to gain a headstart on the competition.? The report acknowledged that
?[t]he fact that Paxil failed to separate from placebo according to four of the outcome measures
in the [329] study could be used as a weakness by competitors and may be an obstacle if filing
for an extension of the product license.? Nonetheless, the report recommended ways to spin the
study to make Paxil the drug of choice in treating depressed children, including:

If successfully managed, this initiative will extend use of Paxil to another

population. There are 2.5 million adolescents suffering from depression in the

USA. This represents a large market, though uptake is likely to be slow. To

tackle this market would provide contact with a large number of who

specialize in pediatrics.

54. In an August 2002 strategic brand plan, GSK continued to list pediatric use,

including pediatric depression, as an opportunity for PaXil, even though it was four years after it

knew the negative results of Studies 329 and 377, and a year after the results of Study 701.

13

1. GSK Provided its Sales Force Off-Label Information about Paxil for
Children.

55. In September 1999, at a training for some of sales force promoting Paxil,
Dr. Karen Wagner, a child told the sales force that depression in adolescents was a
lethal disorder that, if untreated, could lead to suicide and linger into adulthood. According to a
GSK newsletter (Exh. 3), Dr. Wagner recommended Paxil for this population as follows:

Obviously, therapy is needed and Paxil is one of the few pharmaceutical

approaches that has safety and ef?cacy data to support its use in this [adolescent]

patient population. And more data is on its way.

As many of you know, is preparing an indication for adolescent depression

for Paxil next year! clinical study demonstrating the success of Paxil in

treating depression among adolescents will be published in a peer reviewed

journal during first quarter 2000.

56. According to the same GSK newsletter, Dr. Wagner discussed Study 329 (the
results of which had not yet been published), explained that the results supporting Paxil use in
pediatric patients were ?statistically signi?cant,? and stated that a result of this large study,
we can say that [Paxil] has both efficacy and safety data for treating depression in adolescents.?

2. GSK Provided the JAACAP Article to Its Sales Representatives.

57. In August 2001, the PaXil marketing team sent the IACAAP article to all 2,000
sales representatives who were selling Paxil,? including 160 neuroscience specialty
representatives. The article was accompanied by a cover memorandum created by a member of
the PaXil marketing team (?Paxil cover memo?). This memorandum stated in bold type:

This ?cutting?edge,? landmark study is the ?rst to compare efficacy of an

SSRI and a TCA With placebo in the treatment of major depression in

adolescents. Paxil demonstrates REMARKABLE Ef?cacy and Safety in the

treatment of adolescent depression.

(Emphasis in original). 4. The PaXil cover memo also stated that:

Paxil was significantly more effective than placebo with regard to achievement of
both HAM-D total score CGI score of 1 (very much improved) or 2 (much

14

improved), and improvements in the depressed mood items of the and
the 

58. The memo further provided that Paxil ?was generally well tolerated in this
adolescent population, and most adverse events were not serious,? and concluded:

[T]he ?ndings of this study provide evidence of the ef?cacy and safety of Paxil in

the treatment of adolescent depression. 7 Here?s another example of

Glaxo SmitbKline?s commitment to by bringing forth ?cutting edge?

scienti?c data. Paxil is truly a REMARKABLE product that continues to

demonstrate ef?cacy, even in this understudied population.

59. Notably, the Paxil cover memo did not disclose that Paxil had failed to show
statistical superiority over placebo for any of the study?s protocol?speci?ed primary and
secondary endpoints. The memo did not say that adolescents in the study who received Paxil
displayed more suicidal thinking and behavior than those who received a placebo. The memo
did not say that GSK had completed two additional pediatric studies (Study 377 and Study 701),
neither of which demonstrated that Paxil was effective in treating depression in children. The
memo also did not say that Paxil was approved for use only in patients age 18 or older.

60. Although the Paxil cover memo noted that ?[t]his article is for pharmaceutical
consultants? information only? and instructed ?Do not use it with, or distribute to, physicians,?
the memo?s message was delivered to and used by the sales force to promote Paxil. The sales
representatives and managers, who were all compensated and received bonuses based upon
increased sales, including sales for off-label use in children, relayed the incorrect messages of the
AACAP article and Paxil cover memo to falsely promote Paxil as safe and ef?cacious for
children and adolescents to health care providers around the country.

3. Sales Force Used the JAACAP Article to Promote Paxil Off-Label.

61. Relying on the Wagner lecture and AACAP article, GSK sales representatives

encouraged doctors to prescribe Paxil for children. GSK sales representatives documented their

15

doctor visits in ?call notes? that were recorded in the notes that sales representatives? routinely
prepared at or about the time of calls on prescribing physicians to record what had been
discussed. These notes were available for review by managers as well as others representatives
and re?ect the one-sided picture that the sales force painted of Paxil?s ef?cacy and safety for
treating childhood depression. These call notes also demonstrate that the sales force ignored the
Paxil cover memo?s instruction not to use the JAACAP article with physicians.

62. The call notes written by GSK sales representatives repeatedly re?ect their off?
label promotion of Paxil, including the following:

?Left water fountain. Reviewed [article on] Paxil adolescent MDD. Emphasized

signi?cance vs. placebo, study size. . . . Had reviewed article. Cited data to help

underscore to parents/patients Paxil?s utility here. Also important if liability an issue.?

6/27/01 Milwaukee, WI

?Astros game. Discussed Paxil placebo and imipramine study in adolescents.? 7/13/01
Houston, TX

?Detailed doctor on Paxil for major depression in adolescents and he agreed to use PaXil
there.? 6/1/01 Newark, OH

?Dinner and Yankee game with family. Talked about PaXil studies in children.? 8/1/01
Westport, CT

63. It was not until August 2003, after Great Britain contraindicated Paxil for children
and the FDA warned doctors about possible suicide risks, that GSK for the first time asked its
sales representatives to identify doctors on their call lists who treated patients under 18. As of
May 2005, GSK had identi?ed 5,800 child on the lists of physicians for PaXil
representatives to target for PaXil promotions, including by providing samples. Of these, GSK
confirmed that 1,324 were child-only prescribers.

4. GSK Promoted Paxil for Children by Giving Samples to Child 

64. GSK also promoted Paxil for off-label uses by providing free Paxil samples to

doctors who primarily or exclusively treated children.

16

65. GSK policies encouraged its sales representatives to provide samples to all
doctors on their call lists. Because the Paxil call lists included doctors who primarily or
exclusively treated children, GSK caused its sales representatives to give Paxil samples to
doctors who were likely or certain to use the samples for unapproved uses.

66. GSK knew that its samples were being used in this manner, as illustrated by a
survey of sales representatives which showed that the representatives wanted more smaller-dose
Paxil pills, ?which were used for children, elderly, and anxiety patients.?

5. GSK Promoted Paxil for Children During Paxil Forum Meetings.

67. In 2000 and 2001, GSK also promoted Paxil for unapproved uses by bringing top-
prescribing to lavish resorts for Paxil Forum meetings. There were four Forum
meetings each year. Each representative attended two per year, and got to invite two
to each meeting:

68. The meetings were held at expensive resorts such as the El Conquistador Resort
Golden Door Spa in Puerto Rico, the Rio Mar Beach Resort in Hawaii, and the Renaissance
Esmeralda Resort Spa in Palm Springs, California. GSK paid for the lodging,
air fare, and a $750 honorarium. GSK paid speakers a $2,500 honorarium. GSK also paid
spouses? airfare if two cheaper tickets were available for the cost of one full?coach fare.

69. The typically arrived on a Friday morning. Presentations took place
on Friday afternoon and Saturday morning. GSK hosted nice dinners on Friday and Saturday
evenings and paid for entertainment including sailing, snorkeling, tours g. the Bacardi rum
distillery), golf, deep sea ?shing, rafting, glass?bottomed boat rides, and balloon rides.

70. The actor/ comedian GSK hired to emcee one of the meetings told the attendees
?we have a wonderful and unforgettable night planned. Without giving it all away, I can tell

you?you'll be experiencing a taste of luxury.? One complained, ?the style of the

17

conference would have been suitable for a convention of cosmetic sales reps; this is supposed to
be a scienti?c meeting. To me, the music, lights, videos, emcees are offputting and a distraction
(even demeaning).?

71. For many other however, the Forum meetings seem to have had the
intended effect. After the May 2000 Forum meeting in Hawaii, one wrote: 
beautiful location, enjoyable and inn??lled activities, an exciting, cutting edge, informative
educational program, well-presented and organized, all add up to a most valuable and helpful
experience exhilarating!? Another doctor wrote after the Forum 2001 meeting in Palm
Springs: ?Both my wife and I enjoyed the extra care our drug rep gave to us all weekend.?

72. Dr. Wagner spoke and recommended the use of Paxil for children and adolescents
at one Forum meeting in 2000, three in 2001, and two in 2002. Before one meeting at which she
spoke, a sales representative wrote to his supervisor that both of the he had invited
?have high volume and are child specialists, which the program is devoted to.?

73. GSK also used the meetings to relay its incorrect and misleading claims in the
JACAAP article. GSK added Dr. Wagner to the agenda of a Paxil Forum meeting in June 2001
to ?capitalize? on the impending AACAP publication. Dr. Wagner?s presentations during the
Forum meetings were similar to the one she gave to the sale force. Dr. Wagner said adolescent
patients who received Paxil in the 329 study showed ?signi?cantly greater improvement.?

74. A GSK report of the 2000 meetings said that 12% of the attending 
said they would be more comfortable prescribing PaXil for children and adolescents as a result of
the meeting. In written evaluations, numerous wrote that they would increase their
Paxil prescriptions for children as a result of the meeting.

75. GSK tracked the Paxil prescription by doctors who attended the 2000 Forum

meetings. ?Results suggest that the Paxil Forum had a significant impact on Paxil market share

18

in the months after attendance,? said a November 2000 memo for the Paxil marketing director.
?Physicians grew actual market share versus their forecasted share immediately after Forum
attendance. Test physicians grew market share signi?cantly relative to Control physicians.? The
memo concluded that increased Paxil prescriptions due to the Forum 2000 meetings resulted in at
least $900,000 in additional revenue in 2000 alone.

IV. OFF-LABEL MARKETING OF WELLBUTRIN SR

76. WBSR is an antidepressant that has been approved by the FDA for only one use:
the treatment of Maj or Depressive Disorder in adults eighteen years of age or older.

77. From 1999 through at least 2003, GSK engaged in a nationwide scheme to
promote the sale and use of WB SR as safe and effective for indications, doses and populations
that the FDA never approved as safe and effective, and that were not medically accepted
indications. For example, GSK promoted WBSR for:

(1) weight loss and obesity;

(2) sexual dysfunction;

(3) Attention De?cit Hyperactivity Disorder (ADHD), Attention De?cit Disorder

(ADD), bipolar disease and anxiety;

(4) addictions, including to drugs, alcohol and gambling;

(5) patients under age 18, including children;

(6) use as an add-on or in combination with other drugs; -

(7) use as an antidote for the side effects of other antidepressant medications; and

(8) use in dosages contrary to that recommended in the label, with. safety claims

greater than those justi?ed in the label.

78. GSK targeted the promotion of for unapproved uses especially in quality
of life areas, enhancing sex life, losing weight, addressing substance addictions and
attention issues. GSK promoted WBSR as What some sales representatives referred to as ?the
happy, horny, skinny pill.? GSK did so knowing that much of the cost of the unapproved, non?

medically accepted and/or inappropriate uses would be borne by federal health care programs.

79. GSK used the following tactics to achieve its marketing goals for WBSR:

19

(1)

(2)

(3)

(4)

(5)

80.

Publicity Strategies: GSK hired a public relations ?rm to hype small preliminary
studies of WB SR for weight loss, obesity and sexual dysfunction in consumer and
general news media to encourage WB SR sales for unapproved uses;

Speaker Programs: GSK hired physicians to speak to other health care
professionals and recommend unapproved uses for WB 

Details and Samples: GSK encouraged sales representatives to provide one-on-
one sales pitches (?details?) to physicians about off?label uses of WBSR and
distributed samples for uses not approved as safe and effective, such as samples to
child and pediatricians for use in children;

GSK sponsored ostensibly independent ?medical education? events
and/or medical society and grand rounds presentations on off-label WB SR uses
where GSK effectively controlled topics, speakers, content, and participants; and

Indueements: Sham Advisory Boards, Trainings and Entertainment: GSK
used sham advisory boards, sham sales representative trainings and other forms of
entertainment and remuneration to promote off-label usage of WBSR and induce
doctors to prescribe WBSR.

While GSK promoted WBSR for unapproved, non-medically necessary and/or

inappropriate uses, GSK also took steps to evade detection by government agencies and conceal

the real purpose and nature of activities, including making repeated false statements to the FDA

about the conduct and concealing the documents that demonstrated the conduct.

A. Corporate Plans Set Forth Its Intent to Promote WBSR for Unapproved Uses

81.

In a variety of national and regional strategy documents, GSK re?ected its

corporate strategy to promote the use of WBSR for unapproved uses.

1.

82.

GSK Hired A Public Relations Firm to Create Buzz and Drive Sales of
WBSR for Off-Label Uses.

In 1998 and 1999 and through at least 2002, GSK used media plans as part of its

marketing strategy to promote WB SR. These media plans were designed to ?create buzz?

and to publicize off-label uses of WBSR, such as for weight loss or sexual dysfunction in non?

depressed patients. Exh. 5.

83.

For example, GSK hired the Cooney/Waters Group a public

20

relations ?rm, to promote and publicize a GSK?funded pilot study by Dr. Kishore Gadde of
Duke University non-depressed obese patients. Although the pilot study
included only 25 patients who were on the drug for only eight weeks, GSK and Cooney/ Waters
promoted the study in the mainstream media and fostered the coverage of WBSR as a diet pill.
This promotion included preparing and distributing a press release about the study to general
consumer magazines (such as Allure and Redbook), providing Dr. Gadde with media training,
and coordinating with the media ?to make sure reporters and editors have the new data and
understand its significance.? Given the limitations of the study and preliminary nature of the
data, its ?signi?cance? should only have been to researchers considering further research, not to
the general public.

84. Cooney/Waters and efforts generated stories from CNN andiDateline, as
well as tabloids. 6. It resulted in articles with headlines such as ?Bigger than Viagra? It
sounds too good to be true: a drug to help you stop smoking, stay happy and lose weight? and
?Now hat is a Wonder Drug.? As Cooney/Waters itself touted in a September 1999 report to
GSK (Exh. 7), its efforts to promote Gadde?s ?weight study has been carried by: More than 70
local television stations More than 50 local newspapers and consumer magazines nationwide
and in the United Kingdom More than 9 Internet outlets nationwide 12 trade publications
in the United States [and] Media impressions exceed[ed] 15 million (not including wire and
Internet impressions)?

85. One example of the media pick up included the following article in the tabloid

?The Sun?:

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86. GSK also hired Cooney/Waters to publicize results of other off-label studies to

 

 

general and consumer media, including a small study of WB SR to treat sexual dysfunction, and a

later study of WB SR for weight loss in patients with depressive but not depression.
87. GSK also hired Dr. Drew Pinsky from MTV and Loveline as a spokesperson to

deliver messages about WBSR in settings where it did not appear that Dr. Pinsky was speaking

for GSK. GSK indirectly paid Dr. Pinsky $100,000 in March 1999 and $175,000 in April 1999.
22

 8. In about June 1999, Dr. Pinsky spoke on a national radio program and communicated
key GSK WBSR campaign messages. The ?Highlights? included: ?Switching to or adding
Wellbutrin is recommended for people experiencing a loss of libido.? During the program,
among other things, Dr. Pinsky noted that the drug in WBSR, bupropion, could explain a woman
suddenly having 60 orgasms in one night. Dr. Pinsky explained that one of the things he
advocates for people experiencing diminished libido or arousal is WBSR. 9.

88. According to a report prepared on behalf of GSK in 2002, the media campaigns
surrounding use of WBSR for obesity, weight loss and sexual dysfunction reached a total
audience of more 387 million, ?[s]parked sales growt and caused WBSR to be used
increasingly as a ?rst?line product, both alone and in combination with other therapies. Exh. 10

B. Follow?Up on Gadde Study

 

89. Following the pilot study by Dr. Gadde on the use of WBSR for obese non-
depressed women, GSK hired Dr. Gadde and other weight loss specialists to give promotional
talks on behalf of GSK to other physicians and to discuss the use of WBSR as a ?weight-loss
agent.? In these talks, the speakers reviewed the use of WBSR for weight loss in non-depressed
patients and advocated its use for weight loss, despite the lack of FDA approval or substantial
evidence supporting this use. In such programs, Dr. Gadde, a consultant for the Duke Diet and
Fitness Center, presented his study on the use of WBSR in non?depressed patients.

90. However, in the spring of 2000, when Dr. Gadde was preparing the manuscript
about the study for publication, GSK had a falling out with him over his insistence on
emphasizing certain safety warnings and his refusal to use Wellbutrin trade name.

91. Dr. Gadde was informed by a chairperson at his university, also a GSK
consultant, that GSK would not fund any more of Dr. Gadde?s studies due to his refusal to

remove some of the safety discussion from the article. Clinical Director for their Central

23

Nervous System program, Tim Kuhn, also informed Dr. Gadde in writing that Dr. Gadde should
not have made the decision to submit his own article on the study to the journal Lancet rather
than AMA without consulting with GSK as GSK was his ?partner in publishing decisions that
consider both patient and brand issues.? Kuhn explained to Dr. Gadde the consequences of such
a failure to consult with GSK: ?It is unlikely that additional support for other investigaton
initiated projects will be embraced enthusiastically if there is no input from GW
[GlaxoWellcome, predecessor] or if input from GW is not considered.? Exh. ll.

92. After this falling out, national marketing team increasingly utilized other
physicians, including Dr. Ken Fujioka, an endocrinologist specializing in weight loss treatments,
as its spokespeople to present the Gadde study, rather than Dr. Gadde himself.

93. GSK hired Dr. Fujioka in September 2001 to train the WBSR sales force on using
WBSR for weight loss. Dr. Fujioka is known as the ?Fat Doctor? due to his focus on diet and
weight loss. Dr. Fujioka does not treat depression and thus does not even utilize WB SR for its
only on?label use. Dr. Fujioka?s talk on the effects of WBSR on weight included slides claiming
WB SR is associated with significantly more weight loss than placebo and that 77% of patients
treated with WBSR 400 mg/day achieved more than 5% weight loss. This presentation also
included claims about the effectiveness of WBSR to treat obesity in non?depressed patients.

94. GSK sales force members utilized Dr. Fujioka in programs and sales calls to
discuss the weight loss effects of WBSR. Some examples of the call notes re?ecting 
sales force use of Dr. Fujioka include:

program with local and visiting (Ken Fujioka). Goodman

presented on WSR in ADHD and Depression, outstanding job, Fujioka presented

the weight data which sparked alot of participation from the audience as well as

feedback . . . 11/3/01 Durham, NC

?Followed up on sib. Enjoyed. Liked Fumioka talk benef of w/ wsr.? 10/26/01
Hudson, FL

24

?she loved fujioka..invited her to hear hudziak in january? 11/26/01 Brockton,
1W1 

?Dr Fujioka lecture on weight studies in Boston. Send him info on the use of
methadone and 11/9/01 Lynn, AM

?She came to the Fujioka program and I would expect to see her WSR numbers
increase based on the weight loss data he presented tonight. . . . thought we should

really spread the word about these studies? 3/21/02 Redwood City, CA

?he says dr fujioka was great? he walked out of his of?ce after the tele conf and
implimented options he spoke abou 6/2 7/02 Bangor, 1W4

C. Operation Hustle: National Campaign for WB SR to Treat ?Co-Morbidities?

95. In 1999, GSK also instituted ?Operation Hustle? a national sales campaign. In
meetings with national sales and marketing personnel in about 17 cities around the country, GSK
introduced a new approach to selling WBSR by promoting WBSR for ?co?morbid conditions?
that were not FDA?approved uses for WBSR, but may also exist in depressed patients, such as
weight gain, sexual dysfunction, and ADHD. GSK instructed its sales force to promote WBSR as
increasing the neurochemical agents norepinephrine and dopamine, and thus effective in treating
?co?morbid? disorders thought to be connected to levels of norepinephrine and dopamine, such as
ADHD, addiction, and craving.

96. In April 2000, strategic plan for WBSR identi?ed as sales opportunities
off-label uses such as ADHD, anxiety, lethargy and bi?polar disorders and listed WBSR use in
combination with other antidepressants to their treat side effects as a growth opportunity.

97. off?label marketing strategies worked. Less than a year later, GSK noted
that ?use for treatment of antidepressant induced sexual dysfunction has increased due
to product positioning,? and that it was a ?[p]roduct of choice for adding . . . patients who
experience sexual dysfunction or efficacy poop-out.? Sales increased approximately 34% from

2000 to 2001, far in excess of the market rate of growth for antidepressants.

25

98. Sharon Sharo, the Director of WB SR Marketing, presented to the management

team the plans for WB SR for 2001 and included as WBSR ?Growth Drivers for 2001?:

Completed 2 Obesity trials - results presented [at conferences] . . .

- Obesity study investigating the ef?cacy and tolerability for WBSR in
overweight and obese women published in Obesity Research 9/01
(Gadde).

- WBSR was effective and well tolerated for weight loss at 8 weeks with

sustained [sic] the weight loss through the continuation phase.

99. Sharo also explained that objectives of speaker training for WBSR
included ?Present and position Gadde and Anderson weight data? despite the fact that the weight
data was both off-label and extremely preliminary. She also noted that the December 2001 I
Speaker Training in Fort Lauderdale, Florida would include a key talk by Dr. Fujioka.

100. In August 2001, Strategic Brand Plan for WBSR noted under
?opportunities? an ?increased awareness of sexual dysfunction and legitimacy of treatment of
sexual dysfunction in non?depressed patients.? The Brand Plan also stated that GSK will
?[a]ggressively support the ef?cacy and utility of WBSR with new clinical data? and ?[t]hrough
non-promotional means (MI letters, publications etc.) optimize use of strong clinical data for
prevalence of antidepressant induced sexual dysfunction, comparison vs. key competitors in
depressed and non-depressed patients for weight loss and 

101. GSK also pushed throughout the company the message to promote WBSR as an
?add?on? drug to treat co?morbidities side effects of other drugs) and for combination
therapy. For example, in a 2002 Business Plan forwarded by a Regional Sales Director in the
New England Region, a manager set forth the following strategy to grow market share:

Increased focus on D1 Medicaid High potential Prescribers: Target Medicaid areas

With strong messages about the bene?ts associated with NE and DA (the

components of WBSR) LOW sexual dysfunction, impact on weight,
cognition, lethargy and smoking cessation . . . Develop Medicaid Champions to

26

disseminate WBSR messages . . . increase the switching/adding for sexual
dysfunction.

102. Other business plans also encouraged growing WB SR sales by utilizing ?weight

loss data? and promoting the product as ?add-on therapy to These plans also included
a speci?c focus on physicians prescribing for Medicaid patients.
D. GSK Used Speaker Programs to Promote WBSR for Unapproved Uses.

103. GSK used speaker programs to spread off-label information about WBSR. GSK
trained and paid physicians to speak to other physicians at thousands of promotional events per
year that were organized by sales representatives and managers. Many of these events
included false and/or misleading claims about WB safety and ef?cacy for unapproved uses.

In these talks on behalf of GSK, the speakers recommended WB SR for a wide variety of 
unapproved uses, including for weight loss, to treat sexual dysfunction, ADHD and other
attention disorders, and even for patients with bulimia or who were abruptly discontinuing alcohol
(both of which were speci?cally contraindicated in labeling).

104. GSK paid physicians to attend lavish meetings, in places such as Jamaica, during
which GSK promoted WB SR for off?label uses. These meetings were intended to reward
physicians who were writing a large number of WBSR prescriptions and induce physicians to
write more WBSR prescriptions, including for unapproved uses. Sales representatives? call notes
re?ect the off?label discussions and purpose of these meetings:

?Jamacia Discussed role of WSR in treating depression, ADHD, and obesity?
1/27/0] NY, NY

. . Wellbutrin Speakers Training Jamaica lnteracted several times. He was
interested in meeting someone from Marketing about soft money I told him to
talk to [Marketing Director] Lafmin Morgan which he did.? 1/28/0] Durham,
NC

?really enjoyed Jamaica told of successfully using Welb in pt 
1/30/0] Minneapolis, 

27

 . . had a wonderful time in jamaica with well sr marketing. spent some time

with tom and bill which was great. he is eager and ready to talk for us. numbers

are re?ecting a large increase in new i think he gets the picture. sched. a

reprint mastery for the group in his of?ce on the 16th . . 1/31/01 Quincy, 11M

105. In late 1999 or early 2000, GSK established a national WBSR speaker program
known as PRIDE (Peer Review of Intimacy, Depression and Ef?cacy) that featured many off?
label speakers. GSK determined that its PRIDE dinner pro grams yielded an approximate 280
percent ?return on investmen 

106. GSK representatives, including managers, attended every PRIDE program. GSK
obtained copies of the presentations and invited to speak most frequently those speakers who
effectively promoted off?label uses of WBSR. Sales representatives and managers invited the
key speakers back to Speak over and over again across the country and touted them to their
colleagues, sometimes precisely because of the off?label messages and their ability to increase
sales of WBSR,

107. GSK paid such speakers in the range of $1,000 to $2,500 for a one hour program.
Because many of the speakers traveled the country making virtually identical presentations at
each location, little or no additional preparation time was necessary. Moreover, the same
speaker might be paid three times a day for making the same or similar presentation at breakfast,
lunch and dinner in a single day. Some speakers would not even agree to come to a territory to
speak unless they were guaranteed a ?six pack? of speaking events at approximately $2,000 each,
for a total of at least $12,000 for the two day trip. This amount far exceeded the amounts they
were otherwise paid to practice medicine or lecture as university professors.

1. Dr. James Pradko

108. Dr. James Pradko was one of top WBSR speakers from 2001?2003. From

2001 to 2002, he was paid half a million dollars per year for speaker programs about WB SR and

28

nearly a million dollars in 2003 alone. Dr. Pradko was also hired by GSK to present at sales
representative training sessions?both initial and advanced sales training?and was repeatedly a
presenter at WB SR National Speaker Training Meetings. Dr. Pradko, whose specialty is
family practice, was also appointed to National Advisory Board.

109. Dr. Pradko traveled to every GSK sales region to present his standard
presentation, ?The Neuroreceptor Basis of Initial Antidepressant Choice.? In 2002, Dr. Pradko
made this presentation at more than 300 promotional speaker events.

110. Dr. Pradko?s presentation was permeated with off?label claims about WBSR.
Among other claims, Dr. Pradko represented that WBSR could be used for weight loss, ADD in
pediatric patients, chronic fatigue marital dysfunction, erectile dysfunction, addictions
and chemical dependencies, attention disorders, low energy in anxious patients, sleep disorders,
restoring REM levels of sleep, restoring libido and a healthy sex life, and treatment of pregnant
women. Dr. Pradko also told attendees that WBSR could be used as an ?add-on? to treat SSRI
side effects such as ?poop on sexual dysfunction and weight gain.

111. Many of Dr. Pradko?s claims were contrary to label. For example, Dr.
Pradko asserted that he put all of his pregnant patients 011 WB SR and further claimed that the
FDA said that it is safest antidepressant in pregnancy. prescribing information,
however, speci?cally cautioned that the drug ?should be used during pregnancy only if clearly
needed? and that ?there are no adequate or controlled studies in pregnant women.? Moreover,
after animal studies were done, the FDA updated the label for WBSR in March 2007 to
Pregnancy Category because ?it did appear to cause harm to the fetus in previous animal
studies.? According to the updated label, these studies, there was an increased risk of birth
defects and lower fetal weights when the medication was given to pregnant rabbits.?

112. Dr. Pradko?s recommendations to use WBSR use in treating sleep disorders are

29

likewise called into question by WB label. The label cautions that in placebo-controlled
trials, between 11 and 16 percent of patients receiving WB SR experienced insomnia. Even
own marketing department recognized that ?[i]nsomnia is a common concern/comorbid
condition within the depressed patient population and bupropion [the operative molecule in
is associated with increased insomnia.?

113. Similarly, Dr. Pradko?s claims advocating WBSR use in pediatric patients
contravene the drug?s FDA approval, which was approved only for patients 18 and older. 
prescribing information warned that the safety and effectiveness of WB SR in pediatric patients
has not been established. Moreover, as noted above, in October 2004, the FDA required all
antidepressants including WBSR to carry a black box warning that describes the increased risk of
suicide and suicidal thoughts and behavior in children and adolescents given antidepressants.

114. Despite its off?label content, GSK managers around the country and at
headquarters enthusiastically embraced Dr. Pradko?s messages and his standard talk using a
baseball analogy known as the ?baseball diamond talk.? Sales representatives repeated and
reinforced Dr. Pradko?s off-label messages in their calls upon physicians. For example, in July
2000, a northeast marketing development manager emailed the national brand directors:

First of all, congrats to you and your entire WSR team on a great WSR Univ!

Using Dr. Pradko?s baseball graphic of neurotransmitters, you guys have hit a

grand slam. The numbers, the incremental growth, What a success story. (N ow I

know why you called them programs.)

115. In addition to live speaker programs, GSK actively promoted Dr. Pradko?s off-
label messages with an audio cassette version of his lecture. From at least 2000 until into 2003,
GSK purchased and distributed to physicians hundreds, if not thousands, of audiocassette tapes

of Dr. Pradko?s standard lecture with the off-label marketing messages (the ?Pradko tape?). The

sales force re?ected this and the impact on sales in their call notes, including the following:

30

?Raved about Pradko (could hear better on tapes than at program in A.C.) and the
fact that he has increased his WSR use EVEN in certain types of pts.?
4/25/01 Vineland, NJ

?followed up w/ pradko tape, dr was so happy to have it, wants bubble sheets too,
scheduled to speak to corporations in the area in march, reminder on wt loss data,
adding sr, ?rst line therapy? 2/11/02 Bridgewater, NJ

?Stressed the Pradko Tape and he said she will listen to it on the drive back home
tonight and he liked the analogies and he said he had just written for the 150 for
13yr ld girl that was on adderall and becoming combative but doing better with
the add. He said he is starting slower and lower and seeing better compliance to
start it on 10/29/02 Wellston, M1

?told about morning program with pradko in march. has listened to half the pradko
tape already and said he would come to the program.? 1/28/03 Battle Creek, MI

?She raved about the Pradko tape, has listened to it 3 times, much less commercial
than the teleconference, loved the information, uses it daily now. I also gave her
WSR bubble sheet tear?offs, which she likes and will use. Finally went over XL
coming very interested in this.? 6/11/03 Grand Rapids, M1

?went through all products and then went through all reasons to use well xl and
100% conversion. pradko tapes and he said he would go to the program.?
10/22/03 GA

116. In the spring of 2002, a GSK marketing development manager worked with Dr.

Pradko to prepare a DVD of Dr. Pradko?s standard talk. GSK paid for the development costs.

Although the DVD purported to be independent medical education, it was in fact the promotional

talk Dr. Pradko gave on behalf of GSK and developed into a DVD at request.

117. Dr. Pradko provided the DVD to the southeast region of GSK for a pilot project,

with the hope that the company would purchase the rights to use the DVD nationally. The

Regional Sales Director at the time, Anne Whitaker, supported the project and accompanied a

sales representative to a physician?s office to View the DVD. Although Whitaker observed the

content of the DVD at that time, including the off~label messages it contained, her team

continued to distribute and play the DVD for physicians around the region.

118. In one month, GSK sales representatives in the southeast played this DVD for

31

physicians approximately 900 times. The representatives raved about the ?independen CME
effectiveness in persuading physicians to prescribe WBSR with comments such as ?This
DVD has been the best selling tool for me yet. It has not only helped me reach customers that
would not attend programs but also teach myself and customers the best way to use 

2. Dr. James Hudziak

119. In standard presentations that were delivered hundreds of times at GSK PRIDE
and local speaking events, Dr. James Hudziak, a child advocated using WB SR for a
wide range of off-label treatments including ADHD, addictions, sexual dysfunction, obesity,
weight reduction, bi-polar disorders, addictions and bereavement. Dr. Hudziak?s off?label
messages were in slide presentations he provided to GSK prior to his talks on behalf of the
company. Sales representatives were thrilled with the impact of Dr. Hudziak? off-label
messages, as re?ected in their call notes, including the following:

?Lunch with the group today. we dsicussed the use of WSR to treat ped with

ADD and ADHD problems. I used the Hudziak and Wilens articles to discuss

WSR advantages. They all agreed.? 5/10/01 Atlanta, GA

?Follow up on Hudziak SIB. He thought Hud was interesting and wanted to read

everything Hud talked about. Need to follow with all the studies mentioned in the

SIB, probably Sex Monograph, Rush, etc.? 4/22/02 Marion, OH

?disc what hudziak says in regard to and adhd.? 9/9/02 Franklin, TN

?hudziak approp pt pro?le for obese/ smokers adhd/weight loss potential, the

higher the BMI, the more you?ll lose said he would try? 9/10/02 Clearwater,

FL

120. Not everyone was as impressed with Dr. Hudziak, however. According to one
sales representative, one physician who attended ?thought [Dr. Hudziak] was a drug whore.?

121. Dr. Hudziak?s talks and messages were well?known to senior managers at GSK.

His slides were circulated among the members of the sales force, including to managers. He

spoke at both speaker trainings and national advisory boards. Senior marketing managers

32

attended his talks. GSK managers around the country regularly booked Dr. Hudziak for speaker
engagements and repeatedly encouraged others to book him in their regions, even though they
knew his slides and presentation contained off-label information.

122. WBSR Brand Director Lafrnin Morgan and Regional Sales Director Mike Delea
attended Dr. Hudziak?s GSK sponsored talk in connection with the arrival of the Tall Ships
?otilla in Boston in the summer of 2000. Delea congratulated the team that organized the event
noting that ?Dr. Hudziak gave a solid presentation on the effectiveness of The weather
was perfect, along with the boat cruise and viewing of the Tall Ships.? Exhs. 12?15.

123. Sales representative comments concerning this event include the following:

?wants to go to the 4pm tall ships.  - will get back to him if we decide agst kids.
don?t think we numbers are way to imp. to us.? 06/20/00 Boston

?con?rmed 3 tix for tall ships for doc and kids.? 07/07/00 Randolph, MA

?Still talking about Bermuda trip. Wants to play golf at Ipswich CC. Setting it up
for Sept. Looking forward to Tall Ships.? 07/13/00 Salem, MA

. . . r/t Hudziak program in Providence in Jan. Said she Dr. had heard him at

Tall Ships and Dr. loved him. Her prescribing in growth track Show this!?

12/15/00 New Bedford, AM 1

124. Dr. Hudziak was also a popular moderator for advisory boards. He was hired by
GSK to lead numerous local and Special Issue Boards, where he presented off-label information
and encouraged other physicians to use WB SR for on and off-label uses.

125. For example, Dr. Hudziak was a featured speaker at a Regional Advisory Board
for the northeast region in August 2000 at the airmont Princess Hotel in Bermuda. Dr. Hudziak
was paid $5,000 and he and his wife were treated to accommodations and entertainment for the
weekend, which Dr. Hudziak described as a vacation. Eth. 16-18.

126. The GSK manager who organized the event solicited input from the GSK sales

force as to which doctors to invite in order to impact sales. He asked managers to nominate

33

attendees by providing information on their key ?customers? (physicians), those customer?s
prescribing habits and what the sales manager would ?wish to achieve with [the] customer . . . in
an effort to obtain the greatest ROI [Return on Investment] . . . Exh. 19.

127. GSK then selected doctors to attend in order to impact their prescribing of GSK
drugs. The organizers were provided instructions the sales team?s goals for each physician,
including ways to increase their use of WBSR off-label. For example, the sales team noted that
one doctor ?is very pleased with the use of WB SR especially with its effectiveness in ADHD.
Please utilize his positive experience and enthusiasm of WB SR to in?uence other clinicians.?
For another: ?Dr. is a Child and I would like the safety and ef?cacy of a ?rst
line antidepressant and treatment option for ADHD to be relayed to him.? 20.

128. One physician was told that he was invited to ?sit for 4 hours, share your thoughts
around WSR, get paid at a nice place in Bermuda? and he was invited because he was ?the
number one potential doc in the entire state of Maine prescribing anti-depressants.? The event
included a four?hour meeting in three days in Bermuda. By noon Saturday, the ?work? was done
and GSK provided meals, activities and an evening dinner cruise. 21.

129. The Bermuda meeting presentations included numerous recommendations for off-
label uses of WB SR by Dr. Hudziak. Moreover, sales force statements before and after the
meeting demonstrate the purpose of the meeting was really to encourage prescribing of WB SR,
and not to gather needed consulting about WBSR, including:

?will be attending rabs program in Bermuda 8/ 1-8/13: low market share but high
volume target. . 07/05/00 Westerly, RI

?She spoke highly of their trip to Bermuda and of riding around on a scooter! She
like I?Iudziak?s talk, and is increasing her usage of 02/01/01 Greenland, NH

?He attended the Bermuda RAB this past August and he has increased his
prescribing of WellSR? 12/13/2000 email re: Marlborough, 11M physician

34

130. Dr. Hudziak was also a Speaker selected by GSK for ostensibly independent CME
events relating to WBSR. In fact, in the summer of 2002, Dr. Hudziak expressed concern
because a new Vermont law required him to report the large amount of compensation that GSK
paid him to speak on its behalf. To avoid disclosing how much he was receiving from GSK, Dr.
Hudziak informed GSK that he would only do CME events, not promotional events.

131. GSK therefore arranged a series of purportedly independent events where
GSK scheduled the event and selected the speaker (Dr. Hudziak) but arranged for a CME
vendor, Primary Care Network, to ?accredit? the events.

3. Other Physician Speakers

132. Besides Dr. Pradko, Dr. Hudziak, Dr. Gadde and Dr. Fujioka, many other GSK
physician speakers for WB SR also used presentations that promoted off-label uses. These
doctors were paid by GSK for such speaking engagements and spoke at GSK?sponsored events.

133. For example, Dr. Norman Sussman?s standard PRIDE presentation incorporated
representations that WB SR promotes weight loss, including in non?depressed patients. Dr.
Sussman also advocated using WBSR to treat ADHD, smoking cessation, SSRI side effects,
chronic fatigue restless sleep, and Parkinson?s disease.

134. Dr. Sussman also made claims that improperly minimized or contradicted the
drug?s FDA-approved label. Dr. Sussman represented that seizure rates were either
equivalent to or less than the rates seen with even though no head?to?head trials studied
comparative seizure rates and the seizure rate listed for WB SR in its label is higher than some
other antidepressants. Likewise, Dr. Sussman suggested WB SR be used to treat patients with
eating disorders, even though the label contraindication such use because of seizure risk.

135. GSK speakers Drs. Sarah Atkinson and Anita Clayton also recommended WB SR

for weight loss in non-depressed patients, among other off-label uses. Dr. Jeffrey Green

35

presented WB SR as a treatment for cocaine and alcohol addictions and ADHD. In doing so, Dr.
Green, also improperly minimized FDA-required seizure risk. Dr. Croft recommended
WB SR for the treatment of sexual dysfunction, for weight loss, ADD, chronic pain and children.

136. GSK representatives attended every PRIDE event and were well aware of the
speakers? off-label claims. Leading speakers such as Drs. Pradko, Hudziak, Sussman, Clayton
and Atkinson, Croft, and others spoke dozens of times a year and were highly sought after by
GSK for such events. GSK used these speakers to promote off-label use of WBSR by frequently
employing them as speakers, with full knowledge of the content of their presentations.

137. By at least October 2001, a GSK sales representative had noti?ed senior GSK
managers of the use of speaker programs to promote off-label uses, including to promote WBSR
for children and ADHD and, in subsequent months, for weight loss. iExh. 22. The representative
pointed out the evidence of the off?label speaker programs in his colleagues? call notes.

138. When this representative did not receive a response, he escalated his complaints
to heads of human resources and compliance. In his complaint, the representative noted
that he had ?come forward with the truth, which could save the reputation of GSK, and millions
of dollars in ?nes.? 23. He later also wrote to GSK Chief Executives Robert Ingram and
David Stout about his complaints. In early 2002, GSK initiated a compliance investigation that
con?rmed many of the representative? 8 allegations, including the use of WBSR speaker
programs to promote WB SR off-label and use of a spa program to entertain physicians.

139. The complaining sales representative was offered an unusually favorable
severance package, including relocation payments and keeping the company car.

140. Although a manager admitted during internal investigation that he had
been told by the sales representative that the speaker programs were off?label, and although

another sales representative con?rmed that the manager was aware of the off?label nature of the

36

programs, the manager received only a ?verbal warning.? Moreover, although the Chief
Compliance Of?cer noted that off-label discussions by GSK speakers were ?normal? 
common) (Exh. 24), no action was taken to investigate further and the off-label promotion
continued.

A. Sales Representatives Repeatedly Promoted Off?Label Uses of WB SR.

1. GSK Immersed Its Sales Force in Information on Off?Label Uses.

141. GSK actively encouraged its sales force to promote WBSR for off-label uses.
From the time of their introductory sales training and throughout their tenure with the company,
sales representatives were bombarded with information about off-label uses of WB SR, including

Dr. Pradko?s standard presentation at new representative sales training (every GSK sales
representative who sold WBSR was also provided his or her own personal copy of Pradko?s
standard presentation, replete with off?label claims). Exh. 25.

142. Sales representatives were provided with multiple copies of the results of GSK-
funded studies on weight loss in the non-depressed. For example, in June 2001, GSK distributed
a memorandum to its WB SR sales force Iwith new clinical data on the drug?s impact on weight
loss in non-depressed obese patients. GSK also distributed to its sales force the Gadde study and
other studies of the use of WBSR in patients who did not have a diagnosis for depression.

143. GSK required the WBSR sales forces to take a home study course that included a
review of studies on the offwlabel use of WBSR for weight loss. GSK required a mandatory
written ?knowledge certi?cation? on the offwlabel weight loss data in nonmdepressed patients and
other tests on off?label material about WB SR for ADHD.

144. Although representatives were ?told? that they were not supposed to use this
information af?rmatively in promotion, they were required to ?role-play? scenarios with their

managers where they could use this off-label information. Moreover, their performance was

37

judged and their bonuses based on sales goals that re?ected all sales, including off-label sales.
145. GSK sales representatives also proactively promoted the results of studies of non?
depressed patients treated with WB SR for weight loss and sexual dysfunction despite the lack of
any FDA-approval for these indications. Similarly, GSK directly promoted WBSR as an ?add
on? combination therapy to address SSRI-induced side effects, such as weight gain, sexual
dysfunction, and so-called ?poop out? or loss of energy. Thus, emphasis on various off?
label uses translated into direct promotion to prescribing physicians by the company?s sales
representatives and was re?ected year after year in the sales representatives? call notes. GSK
took no action to correct the off-label marketing efforts documented in thousands of such call
notes during the relevant time periods. The following are just a few of the many instances:
?Killer detail today on SR. She wasn?t seeming to know much about it but the line
Happy Horny and Skinny was a good line for her today and we really got into the

whole conversation? 2/1/01 Corvallis, OR

. .we talked about in combo. with a ssri as well as using it in non depressed
women for sexual dis? 2/16/01 Millstadt, IL

?Wants to golf; Reminder on Happy horny skinny pill;? 5/9/01 Bethel Park, PA
?Wellbutrin SR for the treatment of cocaine addiction.? 8/9/01 Belle Mead, NJ
?Great conversation on WSR new wt loss study~augmenting for sex side affects-
brought in rest of breakfast from NW health-loved it! Gave me more time to discuss

the off label uses?ie Bipolar, ADD, Poop ou 8/20/01 Arlington thz?s., IL

?Nice follow up to last visit regarding use of WSR for anxiety, PTSD,
and social phobia.? 9/26/01 Santa Fe, NM

?asked to prescribe in overweight also any with addictions need dopamine
and will give to them? 3/6/02 Trenton, NJ

?Quick positive points and talked about why I was there. Nondepressed women
libido but he wouldn?t bite.? 3/11/02 Seattle, WA

?WBsr for your couch potatoes, happy, horny, skinny pill? 8/3 0/02 Folsom, CA

?Told him the ?happy-horny?skinny? line which he loved. Makes it easier to

38

remember the se profile.? 10/29/02 Grand Rapids, MI

?quick hello and reminders was in a hurry just reminded of the happy horny
skinny pill great for over the holidays? 11/25/02 Yellow Springs, OH

?talked to dr about using for sexual dis. in his non depressed pat.? 1/2 7/03 
Fallon, IL

146. In addition, although WBSR is not FDA-approved for patients under the age of 18,
GSK targeted child and pediatricians for promotion of WB SR. GSK required sales
representatives to visit certain pediatricians and child repeatedly each quarter. On
these visits, GSK representatives actively promoted WB SR for such off label indications as
and pediatric depression.

147. In these sales calls to child and pediatricians, GSK representatives
also routinely gave out samples of WBSR, knowing and intending that the samples would be
used for patients under 18, for whom the drug was not approved. GSK headquarters kept a
database of all sample deliveries and was thus well aware that its employees were giving samples
of WBSR to physicians who primarily or solely treated patients under 18.

148. This fact was also amply re?ected in the call notes sales representatives made. of
their visits to pediatricians and child The following are a few examples of 
internal reports of off-label promotion of WBSR to pediatricians and child 

?discussed use of wellbutrin in children for depression? 1/26/01 Reno, NV

?good lunch. hit with wilens and adhd. he says that it is effective and helps in

disruptive kids alot. led him to hudziak article to show improvement in

aggressiveness.? 4/20/01 Gainesville, GA

?apt today. Discussed for seems to be writing for these to
indications the most. see primarily children OK on samples? 1/4/02 Aurora, IL

. ?Even though he is a pediatrician, I talked with him about my products, because all

have data in children. (adhd?wbsr; imitrex nasal spray-adolescent migraine). Had a
good talk about kids.? 5/14/02 Abbeville, SC

39

?talked of baseball/told of well in adhd adolesence? 6/14/02 Chattanooga, TN

149. GSK also knew from its own market research from at least 2000 to 2003 that the
main messages being delivered by its sales force in promoting WBSR included repeated off-label
claims for the use of WB SR as add-on, to treat sexual dysfunction and weight gain, for bipolar
disease, for children and the treatment of ADHD. Reports from physicians of the main messages

they received from GSK sales representatives included off?label messages such as the following:

- ?Wellbutrin is indicated for 

- . .effective against ADHD 

- . . good in children who have attention span 

- . .in pregnant patients.?

- useful medication in conjunction with the SSRIS to deal with sexual
dysfunction induced by 

- ?Very good as an add-on medication to other 

?Very effective in add?on therapy in conjunction with other antidepressants?

?People suffering from addiction such as smoking, overeating, or illegal drugs?

- ?To prescribe Wellbutrin for anxiety disorder. ..also discussed using. . .it in

I children and adults for attention deficit.?

- ?It was now indicated for weight loss, as well as the treatment of depression, and
smoking cessation.?

- ?Wellbutrin SR is indicated for generalized anxiety 

- ?That it?s safe, effective for treating depression, and also bipolar illness.?

V. OFF-LABEL MARKETING 0F ADVAIR

150. Advair is a combination drug that is approved by the FDA for the treatment of
certain respiratory ailments under certain conditions. From the time of its launch in 2001 through
at least 2010, GSK promoted the asthma drug Advair for first-line therapy for patients and uses
that were neither FDA-approved nor medically appropriate. Among other things, GSK illegally
promoted Advair for ?all persistent? asthma patients, including speci?cally mild persistent
asthma patients and patients who had not yet tried using just one component of the drug. GSK
also at times promoted Advair for all asthma patients, including even mild intermittent asthma
patients. promotion dramatically increased medication costs for patients who did not need

the?combination of two drugs provided by Advair. It also exposed patients to significant safety

40

risks without demonstrated treatment bene?ts.

151. GSK made false and misleading statements about Advair to health care providers,
causing them to consider Advair safer and more effective than it was and thus to prescribe
Advair to patients for Whom it was not medically accepted and potentially unsafe and
dangerous. This marketng also caused physicians to use Advair for other unapproved uses
beyond asthma. GSK also made false and misleading statements directly to state and federal
health care programs to cause them to pay for Advair and persuade them not to place what would
have been medically appropriate restrictions on the reimbursement of Advair.

A. NIH Guidelines Do Not Recommend First-Line Use of Advair for Mild Asthma.

152. The prevailing guidelines for the diagnosis and treatment of asthma are the
Guidelines for the Diagnosis and Treatment of Asthma. They were ?rst published by the
National Heart, Lung and Blood Institute of the National Institutes of Health (NIH Guidelines) in
1991 and were updated in 1997, 2002 and 2007.

153. Under the NIH Guidelines, patients are categorized into mild, moderate and severe
asthma. Patients with occasional asthma are categorized as mild ?intermittent? asthma
patients. The recommended treatment for mild intermittent asthma is a ?rescue inhaler? (short-
acting?beta-agonist (SABA) or albuterol) on an as-needed basis in response to 

154. Patients who regularly suffer asthma are categorized as having
?persistent? asthma. The NIH Guidelines further categorize persistent asthma patients along a
spectrum from ?mild? to ?severe.? For mild persistent asthma, the Guidelines recommend
treatment with a maintenance therapy, such as low?dose inhaled corticosteroid (ICS). The NIH
Guidelines recommend that persistent asthma patients also use SABA on an as-needed basis.

155 . For treatment of moderate persistent asthma, the 2007 NIH Guidelines

recommend either increasing the dose of ICS or adding another controller medication, a long-

41

acting-beta-agonist (LABA), to the low-dose ICS. A ?controller? or ?maintenance therapy?
refers to medication used every day, long?term, to control asthma 

156. Under the NIH Guidelines, ICS is the recommended ?rst-line maintenance
treatment for persistent asthma patients. The 2007 NIH Guidelines state that are the
preferred treatment option for initiating long-term control therapy.?

157. Advair, best?selling drug, is a combination of two other GSK?owned,
FDA?approved drugs: Flovent (an ICS) and Serevent (a LABA). Advair is predominantly
administered through a proprietary inhaler device called the ?Diskus.?

158. In the asthma context, ?first-line? use refers to the ?rst controller medication a
patient is prescribed. First-line use of Advair in mild asthma patients is not supported by the
NIH Guidelines.

13. Advair?s Initial Approval and Label Limited Its First-Line Use.

 

159. Advair was approved by the FDA in August 2000 for the ?long~term, twice-daily
maintenance treatment of asthma.? The label?s Dosing and Administration section stated:

The recommended starting doses for ADVAIR DISKUS are based upon patients"
current asthma therapy. . . For patients who are not currently on an inhaled
corticosteroid, Whose disease severity warrants treatment with 2 maintenance
therapies, including patients on non?corticosteroid maintenance therapy, the
recommended starting dose is ADVAIR DISKUS 100/50 twice daily. [Emphasis
added].

160. The language in Advair?s label on disease severity and initiation of treatment was
extensively negotiated by the FDA and GSK. GSK understood and agreed that the label
restricted ?rst?line use of Advair for ?mild? asthma patients. These were patients for whom
?long?term, twice-daily? use of Advair was non? medically accepted and potentially unsafe.

161. None of the pivotal trials submitted to the FDA in New Drug Application

(N DA) for Advair studied the safety and efficacy of Advair for mild asthma patients. Moreover,

42

prior to the launch of the drug, GSK agreed with the FDA that Advair was not medically
appropriate for such patients and represented to the FDA that it would promote Advair only for
those for whom the combination of ICS and LABA was medically appropriate.
162. At the November 1999 Advisory Committee meeting to discuss 
NDA for Advair, Dr. Tushar Shah, Director of Respiratory Clinical Research, stated ?In
[mild] patients, combination therapy would be inappropriate? and think the label that we
provided actually would exclude mild patients, because what we?re saying is that this product is
appropriate for patients in whom combination therapy is appropriate.?
163. After that meeting, the FDA and GSK negotiated language in the Dosage and
Administration section of the label to restrict Advair?s ?rst?line use by mild persistent patients.
164. GSK agreed and understood the effect of the restrictions in the Dosing and
Administration section. Internally, just prior to the approval of the Advair label, GSK wrote:
DeSpite the implication that Advair Diskus is indicated for all asthma, FDA is not
comfortable that Advair be used or promoted for mild disease. They propose to
describe the appropriate patient populations in the ?Dosage and Administration?
section of the label. This section now contains language that allows Advair to be
used in patients currently taking non-corticosteroid maintenance therapy
(salmeterol, LTMs etc), as well as inhaled corticosteroids. In addition, FDA
appear comfortable in allowing Advair to be used in patients currently taking

albuterol if we qualify they have moderate or severe disease. We are submitting
proposed wording to include this patient population.

 

In summary, it now looks like we have a broad indication with specific dosage
recommendations for patients on any maintenance therapy, as well as a subset of
patients taking albuterol only. [Exit 26].

C. The FDA Rejected Application to Include First?Line Dosing
Instructions for Mild or All Asthma Patients.

 

165. In addition, on April 27, 2001, GSK submitted a supplemental NDA to
the FDA seeking a broader ?rst?line dosing instruction by providing additional clinical data.

GSK speci?cally sought the removal of the language in the Dosage and Administration section

43?

that re?ected the limitation on Advair?s ?rst-line indication to patients ?whose disease severity
warrants treatment with 2 maintenance therapies . . . 
166. In February 2002, the FDA rejected and explained:
We do not believe that you have provided suf?cient evidence of ef?cacy to
support this broadened indication for Advair Diskus. . . . In addition, this
supplement did not provide adequate assurance of the relative safety of the

combination product compared to the single component fluticasone for the
proposed population.

167. Notably, the FDA told GSK that Advair had not been shown to be superior to ICS
the recommended treatment for ?rst-line use for mild (and later all) asthma patients. In its
non~approvable letter to GSK, the FDA stated that the pivotal trial of the application, SAS30017,
?failed to demonstrate the superiority of the combination product Advair Diskus to the single
component ?uticasone propionate using the protocol-specified analysis.? Exh. 27.

168. In its ?non-approvable? letter regarding the 2001 the FDA warned GSK
that marketing Advair with these claims could cause the drug to be considered ?misbranded?
under the United States Food, Drug and Cosmetic Act 

169. In March 2002, GSK wrote to the FDA and withdrew its SNDA there are
currently no additional ef?cacy and safety data with which to amend this supplement.?

D. The FDA Increased Warnings About Advair as GSK Studies Revealed Increased Risks.

170. In early 2003, GSK halted a clinical trial on the safety and ef?cacy of 
the Salmeterol Multicenter Asthma Research Trial (or SMART study)?because a statistically
signi?cant number patients on LABAs died from asthma-related causes. As a result, the FDA
added a ?blaclobox? warning to Advair?s label in 2003 that the data ?showed a small but
signi?cant increase in asthma-related deaths in patients receiving . . . The boxed
warning on the current version of the label states: ?Long?acting beta2?adrenergic agonists

(LABA), such as salmeterol, one of the active ingredients in ADVAIR DISKUS, increase the
44

risk of asthma-related deat 

171. In November 2005, after analyzing the data from the terminated SMART study,
the FDA issued an advisory warning against ?rst-line use of LABA-containing products, such as
Advair. The FDA stated:

FDA is issuing this public health advisory to highlight recommendations about use

of a LABA medicine for asthma: LABAs should not be the ?rst medicine used to

treat asthma. LABAs should be added to the asthma treatment plan only if other

medicines do not control asthma, including the use of low-or-medium dose

corticosteroids.

172. The FDA required revisions to Advair?s label again in March 2006 to clarify the
?rst?line restriction and further restrict ?rst-line use to only severe asthma patients?wthose for
Whom a doctor determined ICS and SABA could not control asthma The revised
black box warning and Indications and Usage section of the label restricted ?rst?line use of
Advair to asthma patients whose ?disease severity clearly warrants initiation with two
maintenance therapies . . . (Emphasis added). The FDA also added to the Indication statement
an ?Important limitation of use? that DISKUS is not indicated in patients whose
asthma can be successfully managed by inhaled corticosteroids along with occasional use of
inhaled, short-acting beta2?agonists.? Accordingly, Advair was not approved for patients whose
asthma could be controlled with medium or high dose ICS.

173. I The day after the label revision, GSK noted internally that Dr. Badrul
Chowdhury, Director of Pulmonary and Allergy Products at the Of?ce of New Drugs,
con?rmed that the word ?clearly? limited the first-line exception only to severe patients.

174. In February 2010, the FDA announced that it had conducted ?a meta?analysis? of
studies evaluating the use of LABAs which ?suggested an increased risk for severe exacerbation

of asthma in patients using LABAs compared to those not using In June

2010, the FDA restated that should only be used as additional therapy for patients with

45

asthma who are currently taking but are not adequately controlled on a long-term asthma control
medication, such as an inhaled corticosteroid.?

175. Despite warnings, GSK downplayed Advair?s safety risks to physicians
both before and after the March 2006 label revision and promoted Advair with claims of
superiority, safety and recommended use inconsistent with the safety risks and label revisions?

E. From the Launch of Advair, GSK Promoted Advair for First?line Use by Mild
Patients Despite the Reiection of this Use.

176. Despite the restrictions, the lack of supporting clinical evidence and the
fact that GSK told the FDA it would not promote for such use, GSK promoted Advair for ?rst-
line use in mild persistent and intermittent asthma patients from the time of Advair?s product
launch in April 2001.

177. product launch for Advair was a lavish event attended by thousands of
sales representatives. The event was held in Las Vegas, Nevada, and attended and led by
individuals at the highest levels of GSK management.

178. Advair?s launch trained sales representatives to promote Advair for ?rst-line use
for all asthma patients, including mild persistent and mild intermittent asthma patients. The sales
message was delivered by top GSK executives speaking to the sales force from the stage at the
launch of Advair in Las Vegas, Nevada:

Jim Daly, Advair?s Product Manager, known as ?Mr. Advair,? presented the
company?s sales pitch to the entire sales force: ?Advair is the complete, simple
solution for persistent asthma. The proof proof is everywhere. The proof is in
the package insert. Our label is big, broad and beautiful. The proof is in the
clinical data. We have superiority claims over virtually everything that physicians
are prescribing today.?

Stan Hull, a Senior Vice President, rhetorically asked the Advair sales

representatives: ?The clinical data that supports Advair?you know you gotta just
ask the simple question: What patient with asthma is not appropriate for Advair??

46

 GSK President David Stout told the sales force: ?You?ve got to make Advair the
1St choice, line, for the treatment of asthma.?

GlaxoSmithKline plc?s Chief Executive Of?cer J.P. Garnier instructed the entire
Advair sales force that they could promote Advair as necessary for all asthma
patients by purporting to quote a conversation he had with a doctor as follows:
said, and you can quote him everywhere you want in the [United States],
?He said it would be criminal not to put an asthmatic patient on Advair.? It would
be criminal.?

Exh. 28 (launch presentation DVDs) 28A (selected portions of launch DVDs).

179. Thus, from the time of Advair?s launch, GSK at the highest levels encouraged and
caused GSK sales representatives to make false and misleading statements about Advair?s
indication and clinical support. ?superiority claims? over other drugs, including ICS,
were not only unfounded?they were specifically rejected by the FDA.

180. GSK provided large ?nancial incentives to sales representatives to promote Advair
for unapproved, off?label uses. GSK executives took to the stage in the Las Vegas product launch
and, using images of a slot machine to illustrate the potential for the sales force to make money by
selling Advair, outlined the bonuses available to sales representatives as follows:

Daly: ?There are people in this room who are going to make an ungodly sum of
money selling Advair. . . . That?s the way it should be. When GSK makes money
you make money. The more you sell the more you make. God bless America.?

Stout: ?But I know it takes a little bit more than just good luck a little hard work,
you need what? Extra incentives!  Let?s spin the big [launch bonus] jackpot
here. . . . [Jackpot spins on screen] $5 for every rep for every 100[/50 Advair]

script. I think we can make some millionaires out there.?

Gamier: ?What is the #1 reason why you should love to be a GSK sales rep? 
BONUS Yeah!?

28 28A (DVDs).
181. By spinning the jackpot wheel, Stout demonstrated lucrative launch bonus
plan for Advair that, in addition to all other bonuses, would pay each sales representative $5 per

prescription of Advair 100/ 50 written in their territory. Advair 100/50 was the lowest dose of

47

Advair, and GSK used this incentive to push its representatives to promote Advair for mild
asthma patients.
P. High Level GSK Executives Implemented the Off-Label Promotion of Advair

182. The direction to target mild and newly diagnosed patients for ?rst-line Advair use
came from the highest level of the company and was reiterated by the company?s senior
management, including in presentations to investors.

183. For example, in a June 2002 presentation to investors, Stan Hull, Senior
Vice President of United States Pharmaceuticals, explained:

So, to summarize . . . we have cannibalized the majority of the Serevent and

Flovent business and we are really dominating our efforts now into getting patients

who are inadequately treated on short-acting beta?agonists onto Advair.

184. Hull went on to note that GSK was promoting for all patients on SABA, despite
the physicians? reluctance. He asserted: ?It?s potentially a fatal mistake to manage a patient only
with a short~acting beta agonist because of the perception that the disease is mild.? To the
contrary, the FDA had concluded that there were potential increased safety risks from putting
mild patients who did not need the combination product on Advair.

185. In a presentation to investors in March 2004, Hull, accompanied by President of
United States Pharmaceuticals Chris Viehbacher, was even more explicit about intent to
pursue the mild asthma population for Advair, stating: ?One of our strategies this year, or
objectives, will be focusing on this category the mild asthmatic. . . . So our objective in simple
terms this year is to persuade a physician to start their patients on Advair.?

186. Hull admitted that many physicians do not agree with such an approach as
medically appropriate. He stated: ?the biggest objection we get back is, Advair is my medicine of
choice for many patients who have moderate to severe asthma. However, not everybody needs

Advair.? Hull explains response, which is essentially that Advair is the best patient care

48

for all asthmatics, as re?ected in the company?s false and misleading marketing: I am a
physician I want my asthmatic patients to get the best care possible, so why would you . . . not be
giving a patient with asthma Advair.?

187. Hull even bragged to investors about 8 success in promoting Advair for ?rst-
line use in the mild population to investors. He stated:

You may ask yourself how we are doing in this mild segment. We started this

overall approach in 2003 and we started with a share of about 18% and now we are

approaching 34% in this segment, so we are seeing this initiative is working, not as

fast as I would like it to, but de?nitely working.

188. In 2004, Viehbacher, in an investor presentation in London, England, with the
Chairman of the Board of GlaxoSmithKline Sir Christopher Hogg present, emphasized that it
was strategy to push Advair for all asthmatics. He stated: ?The real opportunity for us
with Advair is that we can now convince physicians that there is no such thing as mild or severe
asthma: you have asthma, and you can achieve better control.?

189. At the same meeting, Hull explained: ?So with Advair we want to help physicians
think simply: if the patient is asthmatic, what do I do? We want them to prescribe Advair 100/50
as their ?rst choice for managing these patients.?

190. In January 2006, CEO J.P. Garnier, told investors that the FDA warning
about the safety of Advair should not affect stock price because it is ?not meaningful and
it is not going to have a big effect.? He stated: think products such as Advair are phenomenal
for the treatment of asthma, and they should be used for mild to moderate and severe asthmatics.?
Garnier also explained: ?Physicians are not going to listen to the 

191. These top executives drove the off?label strategies for Advair to keep Advair sales

growing because Advair sales were critical to stock price and investor ratings. For

example, when, in April 2003 Advair sales declined for just three weeks, David Stout, then Chief

49

Operating Of?cer of GlaxoSmithKline plc, sent an email to Viehbacher, President of US.
Pharmaceuticals, asking ?What is happening with Advair? . . . I think we better light a ?re under
the team . . . sooner rather than later.?

192. In June 2004, when investment noticed a decline in Advair?s growth, they
downgraded their rating of GSK stock. The noted that GSK was seeking to grow Advair
in the category of mild persistent asthma ?despite the drug not being recommended in the
guidelines for this level of disease severity.? Exh. 33.

193. In response, Advair brand team was asked to prepare a response for 
senior management, including Garnier, Stout, Viehbacher, Hull, and set forth a plan to increase
Advair?s growth. Exh. 34. The response quoted the Deutsche Bank statement that ?Strict
adherence to the US guidelines would imply that Advair usage should be con?ned to patients with
moderate and severe persistent asthma.? The response also noted that much of the recent sales of
Advair had been for patients who had neither asthma nor COPD. The GSK marketing team
nonetheless stated: ?We are con?dent that the changes that we have made to the selling [Plan of
Action] and the promotional message will drive growth in Q3 and Q4. The changes include: .
Focus on earlier use of Advair, speci?cally in patients who have uncontrolled asthma but are
typically thought of as ?mild? by primary care physicians.? Exh. 34.

1. False and Misleading Promotion of Advair for First-Line Use.

194. From 2000-2010, GSK promoted Advair for unapproved and non?medically
accepted ?rst-line use in asthma by making false and misleading statements about Advair?s
indication and the NIH Guidelines, as well as false claims that Advair was superior to other
asthma drugs, including ICS, for ?rst-line use.

195. From immediately following the Advair launch in April 2001, GSK inundated the

market with its improper marketing messages, sending nearly 2,300 sales representatives to

50

70,000 physicians in the ?rst ?ve days alone. From the beginning, senior managers in
the ?eld also instructed the sales force to promote Advair for ?rst-line use and all asthma
patients, including mild asthma patients. For example, on or about March 2001, a GSK Regional
Sales Director manager forwarded a message to train sales representatives with the leading line:
?Doctor, three bene?ts of treating your mild asthma patients with Advair are: 

196. GSK aggressively pursued a national strategy to ?Establish ADVAIR Diskus as
the Physician?s First Choice for the Treatment of ALL Persistent Asthma.? GSK created and
distributed to its sales force for sharing with physicians all around the country glossy sales aids
that told physicians to ?Prescribe Advair for your persistent asthma patients.?

197. promotion of Advair for all asthma patients and all persistent asthma
patients directly contradicted the NIH Guidelines and the FDA?approved label.

198. promotion of Advair as superior for first-line use was false and misleading
because GSK did not inform health care providers that the FDA speci?cally rejected the
company?s for ?rst-line use of Advair by mild persistent asthma patients. Nor did GSK
disclose that the FDA had reviewed the data and analysis and concluded that the available
evidence did not support Advair?s safety and ef?cacy, let alone its superiority, for patients on
SABA alone, including intermittent and mild persistent asthma patients.

199. The FDA speci?cally rejected the pivotal trial in applicatiOn?
study SAS30017~wfor failure to meet its protocol de?ned endpoints. GSK had submitted a
modi?ed statistical analysis for study SAS3 0017 to the FDA to claim statistical signi?cance, but
the explicitly concluded that the study failed to meet its protocol?de?ned endpoints and
did not demonstrate superiority of Advair over ICS for asthma patients taking SABA alone. The
FDA also noted certain safety signals from the study in this population. Exh. 35.

200. Without informing health care providers of the rejection of the or

51

study or the concerns raised by the FDA, GSK used SASSOOU to construct its core marketing
messages that Advair ?delivers superior control? compared to ICS alone and that
Advair provides ?more free-days? than ICS alone. GSK disseminated this false claim
of superiority to ICS for patients previously on SABA alone in written marketing
materials for Advair and in advertising campaigns for Advair, including in nationally broadcast
pre-recorded teleconferences across the country.

201. Moreover, although the SAS30017 study was limited to moderate to severe
patients, GSK used the study to claim superiority to ICS alone for all asthma patients
uncontrolled on SABA alone. This claim directly contradicted the conclusions when it
reviewed SAS3 0017. In addition, after the March 2006 FDA-required label change, this
promotional claim directly contradicted the ?Important Limitation of Use? in label for
Advair, which stated that Advair should not be used for patients who could be adequately
controlled on ICS alone.

202. GSK also misled prescribers with its ?Myth of Mild? asthma campaign. GSK
trained sales representatives to promote Advair based on the false assertion that mild asthma
does not exist or that patients do not go to a doctor for ?mild? asthma. GSK told physicians that
all of their patients deserve the most effective asthma treatment, Advair. One GSK manager
explained to her team that the portion of asthmatics with mild asthma was essentially non?
existent or ?infinitesimally small.? The same regional manager signed communications to the
regional sales team and outside physicians with the tag line ?If it?s asthma, its Advair.?

203. GSK depicted its View of the asthma market as follows:

52

The Asthma World According to GSK

  
  

Aibuteroli

?caamsmahalm

 

204. GSK sales representatives widely used the ?myth of mild? arguments to convince
physicians to treat their mild asthma patients as though they were moderate or severe, in
contradiction of the NIH Guidelines? recommendations and the FDA-approved label.

2. GSK Deliberater Sought to Convert ICS/Flovent Sales to Advair, Without
Regard to Safety or Medical Appropriateness.

205. GSK promoted Advair, the mo st expensive of its asthma products, even against
Flovent?its own (cheaper) ICS product. Internal training documents refer to Flovent as the
Advair sales representative?s Competition.? GSK also instructed portions of the sales force
to promote Advair based on claims that the physicians could save time and earn more money by
prescribing Advair and with the phrase ?Advair is easy to use for all asthma patients.? 29.
Although Flovent/ICS was the medically appropriate medication for many asthma patients, GSK
promoted Advair for these patients because it was more pro?table. GSK internally stated that
?Advair is now the engine that drives 

206. GSK emphasized to its sales force that a high percentage of patients stay on the
drug that they are initially prescribed, and thus they needed to promote Advair for use earlier in

the treatment paradigm. GSK instructed its sales force to ?please remember to deliver the
53

 magma 102036100 



message ?Make Advair the First Controller? on each and every sales call.? Exhs. 30?32.

207. GSK national marketing managers also explained to the sales force that in order
to realize the opportunity of Advair, they needed to ?Realize that one opportunity is in patients
new to asthma therapy,? who had not even used SABA, and ?Understand that getting your
product on ?rst is the most important thing to do.? Thus, contrary to the general medical
principle of treating patients with only as much medication as they need, sales force
promoted non-medically necessary and off-label use of Advair for all asthma patients with false
arguments of safety and ef?cacy. Exh. 31.

208. Thus, using the diagram below, GSK taught its sales teams ?It is all about Getting
ADVAIR on and ?Advair is superior to Flovent and Singulair.? The selling line GSK
gave the sales force was ?Make Advair 100/50 your first choice for patients on
rescue medication? despite the lack of evidence for superiority in this group, the explicit

rejection of such initial Advair use and the safety risk associated with Advair. Exh. 31.

Advair Asthma
Strategy

Make Advair the First Gontroiler

  

Wb? rain sch-Sun in m. sh?xa?i

 

209. As part of this effort, the GSK central marketing team also incorrectly informed

the sales force that the SAS30017 study showed that Advair was superior to Flovent on every
54

ef?cacy measure for patients on albuterol alone. Exhs. 31?32.

210. Throughout this time period, GSK heavily rewarded Advair sales in its sales force
compensation, but did not reward Flovent sales, despite its medical appropriateness. For years,
GSK refused to provide Flovent samples, despite complaints from doctors. Instead, GSK
explained to physicians that the patients the physicians wanted to prescribe lovent should be
prescribed Advair?vwith one sales representative saying GSK could not ?ethically? provide
samples of lovent.

3. From 2006-2010, GSK Continued to Misleadingly Promote Advair for First-
Line Use Despite Additional Warnings and Restrictions by the FDA.

211. Despite the additional restrictions on ?rst-line use in the Advair label placed in
March 2006, GSK continued to promote Advair for ?rst-line use by falsely claiming the NIH
Guidelines supported such use and by using the FDA-rej ected study SAS30017 to falsely claim
that Advair was superior to ICS for ?rst?line use.

212. One of anchor strategies for promoting Advair for inappropriate ?rst-line
use after the March 2006 label revisions was based on the number of SABA re?lls a patient
?lled. GSK promoted Advair for patients who re?lled their SABA a certain number of times
(two to four) in the last year. GSK did this by falsely claiming that these patients must be using
their inhaler daily. GSK told physicians that these patients were therefore ?Step 3? [moderate
asthma] patients under the NIH Guidelines.

213. GSK then falsely told physicians that Advair was ?preferred? or ?a preferred?
treatment for these patients under the NIH Guidelines, even though the 2007 NIH Guidelines did
not recommend initiation of treatment with Advair for these patients promotion was
therefore contrary to the first-line restriction in Advair?s approved label to patients ?Whose

disease severity clearly warrants? initiation with combination treatment and also contrary to the

55

Important Limitation of Use in Advair?s label, which stated that Advair was not indicated if a
patient could be controlled on ICS plus occasional SABA.

214. claim as to SABA re?lls re?ecting a lack of controlled asthma was faulty
for several reasons. First, it is common for patients to keep spare SABA canisters in multiple
locations g. home, work and car), and thus the use of several canisters does not necessarily
re?ect how often patients use the drug. Also, NIH Guidelines caution that ?[b]efore increasing
therapy . . . the clinician should review the patient?s inhaler technique and adherence? because
often patients who overuse albuterol are not using their inhaler properly.

215. false and misleading promotion of Advair was re?ected by the sales
representatives in their call notes including the following:

?Advair appro. for ALL persistent asthmatics, inc. 07/26/2001
Doylestown, PA

?Advair for all persistent mild moderate or severe.? 05/16/2001
Kenosha, WA

?Emphasized Advair not just for severe asthmatics but also mild intermittent.?
10/31/2001 Milwaukee, WI

?advair diskus for mild intermittent.? 02/05/2002 Trenton, NJ

?Discussed bene?t of offering to all intermittent asthma patients.? 03/26/2003
Oakdale, CA

diskus for mild intermittent. . . 02/05/2002 Trenton, NJ

GOALS OF THERAPY. ASKED FOR MILD PATIENTS AS
INITIAL 03/27/2002 Fort Wayne, IN

first-line, even mild asthma, superior to singulair and PP 
03/25/2002 Henrietta, TX

Used NIH to close hard that there are NO mild asthma pts. Advair IS the
solution.? 03/04/2003 San Antonio, TX

. .discussed stressing of mild asthma. If there in your of?ce, never 
03/04/2003 Garden City, MI

56

 . .he laughed and said ?you want me to use Advair for every patient?? I said yes,
anyone that is ?persistent? by nih criteria. . 03/06/2003 Alexandria, VA

. .She said that she had heard that the mild asthma cme program was a Advair
03/06/2003 Madera, CA

?Dr. says that she is going to start writing more Advair since she attended the
of Mild Asthma CME in Beverly Hills awhile back. Said the talk was
excellent and Advair was spoken very highly of, which has in?uenced her to
begin writing more of i 03/12/2003 Torrance, CA

?Remind her of the new indication/usage of Advair 100/50 for her patients
suffering from mild to severe cases of asthma.? 06/24/2004 Long Beach, CA

?Asked docs to try Advair line rather than Flovent? 09/7/2004 Revere, MA

no reason not to put on Advair more effective in reducing
albuterol use and increase in free days.? 03/31/2005 Weston, FL

216. promotion convinced doctors that Advair was safer and more effective
than it really was and thereby caused them to use Advair not only for non-medically accepted,
off-label uses in asthma patients, but also for other off-label respiratory conditions, such as
bronchitis, coughs, common colds and wheezing.

217. GSK also did not train its sales representatives to relay the contrary ?important
limitation of use? in Advair?s label, which restricted Advair use by those who could not be
controlled on even with occasional use of SABAs.

218. In 2006, GSK, knowing that it was under federal investigation and that the
government investigators were looking at call notes as a source of evidence, modi?ed its call
note system to use a drop?down menu of approved core messages and anticipated and desired
responses from the physicians. Sometimes there was also a small space for additional comments.
Nonetheless, even in this pre-scripted system, GSK included as one of its approved core
messages that Advair delivered ?more free days? than other asthma products, including

ICS, even though it had not proven such superiority for most patients. Furthermore, in the

57

section for desired physician responses, GSK listed the response ?will use ?rst line.?

219. Following the implementation of this system, in thousands of call notes, GSK
sales representatives re?ected that they delivered the approved core message of ?Advair Diskus
delivers more free days? and in many instances re?ected that the physician gave the
response agreeing to use Advair ??rst line.? Below are a few examples of this pattern:

DISKUS ASTHMA: Approved Core Message(s) Delivered:

Physician?s Response: Will use ?rst line uncontr mild persis.? 06/5/2006 Boca

Raton, FL

DISKUS ASTHMA: Approved Core Message(s) Delivered: ADVAIR

delivers more free days. Physician?s Response: . . . Will use
?rst line for persistent asthma.? 06/13/2006 Schwenksville, PA

DISKUS ASTHMA: Approved Core Message(s) Delivered: ADVAIR

DIKUS 100/50 delivers superior control. Physician?s Response:

Challenge/issue for physician Guidelines ICS 1St . . . Will use ?rst line.?

06/04/2007 Teleford, PA

DISKUS ASTHMA: Approved Core Message(s) Delivered: Advair

Diskus 100/50 delivers superior control. Physician?s Response: Will

use ?rst line keep smoke on it.? 06/20/2007 Orlando, FL

220. In 2009, the Executive Director of Advair Marketing emailed ?innovative ideas?
from a senior manager including once again recommending Advair for all patients: 
favorite thing to say is ?Step 3 [for moderate asthma patients under the NIH guidelines] with
ADVAIR is just a starting place?. Why wouldn?t you give it to everyone. Guidelines are just that
guidelines. . . . I am just being honest with what works. You can?t argue with our success.?
G. GSK Made Additional False and Misleading Statements about Advair.

221. GSK also promoted Advair with other false and misleading claims, including:

(1) purporting to quote the NIH Guidelines? recommendation that physicians

aggressively treat asthma to ?gain control quickly? of while
ignoring??nd omitting from quotes in printed materials??the second half of the

sentence that states patients should be frequently reevaluated to see if they can be
?stepped-down? to less medication;

58

(2)

(3)

(4)

(5)

(6)

(7)

(8)

222.

advising physicians that they should not step patients down from Advair because
doing so could result in a loss of control over the patients? asthma, even though
this advice is directly contrary to the NIH Guidelines and good medical practice;

promoting Advair as a means to reduce steroid use, a claim rejected by the FDA
in 2003. In just the last half of 2003, GSK budgeted over $5 million to train
speakers and held thousands of ?faculty led teleconferences? on topics including
steroid sparing;

promoting Advair to avoid ?airway remodeling? in the lungs from asthma, despite
a lack of substantial evidence or FDA approval for such a claim;

promoting Advair with the unsubstantiated claim of ?increased patient
compliance? despite a lack of evidence or FDA approval for this claim;

promoting Advair as more ?cost-effective? despite a lack of evidence or approval
for this claim, the fact that Advair cost nearly twice as much as ICS alone, the
increased the risk of Advair-related exacerbations and death, and the fact that
Advair was not approved or medically accepted for mild ?rst line use;

promoting Advair 500/50 (?Advair 500?) for COPD patients, even though the
FDA refused to approve Advair 500 for COPD, ?nding that it was not an
approvable dose for safety and ef?cacy reasons. Studies showed that the COPD
patients treated with Advair had a higher incidence of respiratory tract infections
and pneumonia. COPD patients treated with Advair 500 also showed no
documented bene?t over those treated with the lower dose; and

promoting Advair 500 for COPD and with misleading information regarding its
ef?cacy. Even though the FDA denied the ?mortality? claim and approval for the
500 dosage for COPD because Advair 500 continued to increase patients? risk of
pneumonia, GSK nonetheless promoted Advair 500 for COPD patients.

To drive sales of Advair for COPD, GSK also engaged in an ?only 1? campaign

to promote Advair for COPD patients who had previously had only one exacerbation. In April

2008, the FDA approved Advair Diskus 250/50 for the reduction of exacerbations in patients

with COPD with a history of exacerbations.

223.

To support its ?Only One? campaign, GSK made false and misleading statements

about the American Thoracic Society Treatment Guidelines for COPD (the ATS Guidelines).

The ATS Guidelines recommend an combination for COPD patients with one prior

exacerbation only if the patient also has a FEV (forced expiratory volume) of less than 50%,

59

which is categorized as severe COPD. GSK trained its representatives to omit this important
requirement and instead state that ATS guidelines recommend Advair for COPD patients who
had ?only one? exacerbation, thereby promoting Advair for milder COPD patients, contrary to
ATS guidelines. GSK gave sales representatives buttons to wear with the phrase ?Only One.?

224. Moreover, when a sales representative questioned this message as ?not true,? a
GSK marketing manager nonetheless encouraged the use of the false message with primary care
physicians who were unlikely to perform the FEV test. She thus acknowledged that GSK was
promoting Advair for COPD to doctors who did not have the tools to diagnose COPD.

225. GSK continued to direct its sales force in sales training to deliver this false and
misleading message to physicians through at least the spring of 2010.

H. GSK Made False and Misleading Statements to Medicaid Programs to Prevent Medically
Appropriate Restrictions on Advair Reimbursement.

226. GSK presented false and misleading information directly to the Medicaid
programs to block step edits and prior authorization requirements for Advair that would have
restricted non-medically accepted off-label usewedits such as requiring a patient to try an ICS
before a LABA-containing product, such as Advair, unless the physician diagnosed the patient as
having moderate to severe asthma.

227. GSK made the false and misleading claims described above, including the
statements regarding control, superiority to ICS, mortality, and albuterol re?lls, directly to
Medicaid program representatives. GSK also made unfounded claims of Advair?s cost-
effectiveness compared to ICS, despite the fact that Advair is much more expensive than ICS.

228. GSK also tied the payment of state supplemental rebates and discounts to
Medicare Part drug plans to agreements by Medicaid programs and insurance plans not to

?disadvantage? Advair with prior authorizations, step edits or requirements that patients ?rst fail

60

to be treated suf?ciently by other drugs. As a general matter, GSK paid certain supplemental
rebates on its products only if Medicaid agreed not to place restrictions on its products. Here,
however, the proposed restrictions would have only brought recommended usage in line with the
FDA?approved indication and NIH Guidelines. Thus, GSK used its rebate payments to
encourage off-label use of Advair by penalizing efforts to limit Advair?s use for Medicaid
patients to patients for whom it is indicated in its label.

229. State Government Affairs group closely monitored and attempted to defeat
state efforts to restrict off-label use, including step edits, in order to pursue its promotion of
unapproved ?rst-line use and to ensure Medicaid programs paid for these uses. For example, in

2006, Arkansas Medicaid restricted ?rst?line Advair use consistent with the March 2006 label.
Arkansas Medicaid determined that this restriction increased appropriate use of Advair and
decreased Advair utilization by 25% without adverse impact on patient care.

230. GSK internally called Arkansas? efforts to promote appropriate use of Advair as
an ?infestation? and fought to remove Arkansas? step-edit because ?these people [the state
Medicaid employees] talk? to each other. GSK internal documents stated: ?We are facing a
Medicaid step edit in Arkansas. All levels of GSK are involved including [Senior Vice
President] Stan Hull.? In 2008, it appears that GSK provided campaign donations to an
Arkansas legislator who introduced a bill to remove the step edit. One GSK employee wrote to
Stan Hull regarding Arkansas strategy: ?Thanks for your time today and ?God save
political donations?.? Exh. 36.

231. GSK viewed such restrictions on Advair as ?not acceptable? from a business
perspective even though they encouraged more appropriate use of Advair and only would have
restricted unapproved uses of Advair. GSK implemented a ?hold the line? strategy to prevent

other states from adopting step edits like Arkansas?. For example, Hull ?ew directly to an Ohio

61

Medicaid meeting in an attempt to defeat a proposed step edit that was entirely consistent with
appropriate Advair use. GSK falsely argued that Advair ?help[ed] the State avoid costs
associated with asthma visits to emergency rooms across the State by Medicaid?s asthmatic
patients.? proposed alternative step edit (for any patient who had been prescribed a
SABA in the past year) was inconsistent with the FDA?approved label and recommendations of
the NIH Guidelines. Even though Ohio implemented its step edit, reducing off-label use of
Advair, GSK nominated the team that fought the step edit for a ?Spirit Award? for delaying the
implementation of the step-edit by three months. Exh. 37.

False and Misleading Marketing Caused Massive Overutilization of Advair.

232. promotion of Advair was both fraudulent and effective.

233. Numerous studies have con?rmed Advair?s overutilization. Some studies have
shown that 5 0-90% of Advair asthma use is not justi?ed by patients? medical history based on
national treatment guidelines and the Advair label.

234. claims that Advair is more cost-effective than other medications were not
only unapproved or unproven they appear to be false. A 2010 Medco Health Solutions study
of initial maintenance therapies for asthma ?found that the group on a combination 
had asthma?related pharmacy costs that were $215 more per patient per year than the ICS
monotherapy group.? The study also states: ?These ?ndings con?rm that 
combination use is prevalent in mild asthma patients and is associated with increased asthma?
related pharmacy and total healthcare costs with no observed clinical bene?t.?

23 5. A 2010 meta?analysis of studies on initial maintenance therapy by the Cochrane
Collaboration also found that such ?rst-line use of Advair is not justi?ed from a safety or
ef?cacy perspective: ?In patients with asthma who require daily anti-in?ammatory therapy, there

is insuf?cient evidence to support initiating therapy with a combination of inhaled

62

corticosteroids (ICS) and long?acting B2?agonist (LABA) rather than with inhaled corticosteroids
alone.? The analysis showed that ?the combination of ICS and LABA does not signi?cantly
reduce the risk of patients with exacerbations requiring rescue oral corticosteroids over that
achieved with a similar dose of ICS alone.?

VI. GSK PAID KICKBACKS TO PHYSICIANS AND OTHERS TO INDUCE
THEM TO PRESCRIBE AND RECOMMEND GSK DRUGS

236. In order to induce physicians to prescribe and recommend its drugs, GSK paid
kickbacks to health care professionals in various forms, including speaking or consulting fees,
travel, entertainment, gifts, grants, and sham advisory boards, trainings and continuing medical
education (CME) programs. These payments induced physicians to prescribe products,
including speci?cally Paxil, Wellbutrin and Advair, for both on and off?label uses. GSK
provided budgets to the sales teams to entertain and pay physicians to induce them to prescribe
and promote drugs. The allocation of ?customer focus funds? for each sales district
ranged from $600,000 in 2002 to $300,000 in 2008. Of these funds, each GSK sales
representatives received between $15,000 to $30,000 per year to spend on speaker programs,
including breakfasts and lunches at physician of?ces. In a New England regional marketing
plan, GSK instructed its sales force on how to use entertainment as follows:

Extra entertainment is highly recommended to reach as many ADVAIR targets as

possible. Any form of entertainment should be utilized (in accordance with the

AMA guidelines) and a speaker is not required. (Lunches, Clinic Round Tables

and Speaker Programs are not considered extra entertainment. Extra

entertainment is de?ned as taking a customer to dinner or a venue after business

hours E.G. attending the Circuit with a large ADVAIR target). This type of
activity will help you increase your business and total number of scripts for the
national incentive program. [picture of dollars] On a regional basis any
representative that does more than 2 entertainment programs in one week will
receive a $100 American Express Gift Cheque from their manager. We will track

these programs in the regional score card.

237. In some instances, GSK required sales representatives to track prescribing of

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attendees after the entertainment events in order to demonstrate return on investment 
from the event. For example, the Northeast region purchased tickets to Fleet Center events such
as Celtics and Bruins games at a cost of approximately $350 per premium seat. The managers
instructed the representatives that or ROI it?s imperative only KEY Customers attend these
valuable venues,? and required the representatives to complete a prescription tracking form four
months after the event ?to ensure ROI and continued funding . . . Exhs. 38-39.

238. For each drug, GSK also created a group of national ?key opinion leaders?
who were paid generous consulting fees. GSK selected many of these physicians
based on their prescribing habits and in?uence within the community and used the speaker fees
paid to these physicians to induce and reward prescribing of products. GSK used these
individuals to communicate marketing messages focused on the drugs? marketing campaigns at
the time, including off-label uses. Some physicians on speaker?s board have been paid
more than a million dollars for speaking on behalf of the company and recommending its drugs.

239. sales representatives re?ected in their call notes their use of money, gifts,
entertainment and other kickbacks to induce doctors to prescribe GSK drugs, including:

?invited to sib at clearwater will come doc very into QUID PRO QUO wants to be

taken care of for his business. said not into food but likes sports and programs

even into 1i ducks baseball. using wb sr for add on mostly not 1 line use said that

will come as relationship grows? 2/20/01 Central Islip, NY

took him to a Cardinals ball game. We had a great time. He is a Cub fan and his

wife is a Cards fan. The Cards won but he still had a great time. He is detail

sensitive but I did what I could, When I asked for the business he laughed. I didnt

really see the humor in it. How could he think I wouldn?t ask for the business

when I?ve treated his famin to a day at the ball park. 011 well. I?ll see what else I

can do to try to in?uence him.? 7/00 Decatur, IL

?Tkts to Crosby Still Nash. Asked for business in 3/30/00 Oakland
Gardens, NY 

.told him no gol[f] unless we se more scripts for sr I need to see a better roi
from him he 4/7/00 Mans?eld OH

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?took him to lunch and golf lesson. . .gained commitment to increase his use. will
do this every three weeks, great ROI, very cheap.? 5/9/01 Quinton, VA

One doctor in Rockiedge, Florida during 2000 and 2001 
?gave dr. his Nascar will be going back at dr. for a return on
investmen 

?followed up from sending dr. to the race, he was very appreciative, I asked
that he thank me w/ 

?promised to use more since we sent him to the 

?told him he?s going to the pepsi 400 on him to rx w/ both


?attended Rockies game. asked him to prefer GSK products in return, said he
will.? 4/10/01 Aurora, CO

attend knicks-nets game. asked him to help us out in return? 2/4/02
North Bergen, NJ

. . Came out and asked me if I would still be interested in taking him ?shing
w/Dr. Fazal, Kahn, etc. . . HOW BOUT WRITING SOME SCRIPTS AND
GO FISHING ALL YOU 8/10/01 Escanaba, MI

?discussed ?shing when the comes back asked for the business point blank?
7/10/01 Clearwater, FL

said he has been writing tons of SR with good results. He isn?t kidding.
His new scripts are almost 20%. That?s almost 3000. That?s a big change. . . . I
have spent a lot of money on him and it has paid of 5/3/01 Decatur, IL

?Great call with Dr. He enjoyed the pheasant hunt and would like to go again
also he likes to ?sh leverage imitrex wellbutrin and valtrex business to get him to
write more to go on our activity program trips he will help us? 3/8/01 Dothan, AL

now has a 15.5% MS for WBSR. I guess the tennis lessons helped.?
1/28/02 Glen Cove, NY

?Need to get his up, all he wants to talk about is money and where we can
send him. Asked to him to use more wsr.? 5/15/02 Shreveport, LA

?he wants to go to dinner programs and out of town meeting if can. he really can

be bought. said he is using more well 100 in the peds which is mainly what he
sees. didn?t need any samples? 2/28/01 Knoxville, TN

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?always wants money. was giving to a patient when I walked in..showed me
the script.? 2/12/02 Fort Walton Beach, FL

?Asked me about any upcoming programs--he said he could take care of us if we
take care of him. wants to go somewhere for advisory boards or something like

that)? 6/4/03 Gonzales, Louisiana

?Wanted WXL for herself. Told her that I need scripts and switches in return.?
12/10/03 Fort Pierce, Florida

A. GSK Promoted Off-Label Uses Through ?Special Issue Boards? Which Paid High-
Prescribing Physicians To Listen To Improper Promotional Claims

240. During 2000 and 2001 at least, GSK also utilized events termed ?advisory
boards? or consultant meetings and forums to disseminate its promotional messages. Although
these boards were purportedly comprised of ?thought leaders? for the purpose of obtaining
advice from the physician, in fact, the ?advisory? boards were little more than promotional
events coupled with ?nancial inducements to prescribing and in?uential physicians.

241. GSK invited and paid high-prescribing physicians at these events to listen to off?
label promotion and/or to in?uence their prescribing practices. GSK held hundreds of ?Special
Issue Boards? or across the country. Indeed, in the ?rst six months of 2001, for
example, GSK held twenty WB SR ?advisory? boards in and around the Philadelphia area alone.

242. GSK typically paid the physician between $250 and $750 each to attend a local
?advisory? meeting. The payments did not re?ect the value of services. The physician was not
required to do anything but show up. GSK had no legitimate business reason to hire thousands
of ?advisers? to ?consult? with the company about a single drug. GSK used these events as a
reward or kickback to induce the attendees to prescribe and recommend GSK drugs.

243. The ?advisory? meetings were often conducted over dinner at top local restaurants
or hotels or in weekend retreats. At a typical ?advisory board? meeting, physicians would listen

to presentations about drugs, including their off?label uses. The ?advisory? board

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 Pradko, Hudziak, Green and others?were often paid $2,000 to $3,000 to

moderate the events with their standard presentation.

244.

GSK records before and after such advisory boards demonstrate the plan to use

these and other entertainment to in?uence the physicians, rather than to gain advice. For

example, the following are comments of the sales representatives about the attendees of a Special

Issue Board held on July 14, 2001 in Philadelphia moderated by Dr. James Hudziak.

As to one doctor in the Philadelphia area:

?Flyers game. Will carbon every well sr script to prove to me how

much he is using. Said he will now have to start writing 
02/2 7/2001

?Admits to using a lot of samples for some indigent patients, or until
they patients receive script in mail. I still am curious as to where all
well sr are going because we are not seeing them.? 05/02/2001

?well sr?he attended dr hudziak prog. He wrote 92 well sr scripts . . . 
07/20/2001

As to another doctor in Philadelphia, PA:



245.

it in combo and ?rst line, for ADD, etc. . .has heard Hudziak
speak at SIB. . .invited him to RAB [Regional Advisory Board] but need
to con?rm that there is no con?ict due to the fact that he?s heard
Hudziak before. . .is only interested in attending programs where he gets

paid . . go ?gure!? 06/28/2001

?quick stop in to let dr know he is con?rmed for RAB . . . no con?ict
w/ his prior participation at 06/29/2001

?gaining good access to about prior auth . . . annot make
dave 3 program. maybe next yr if we do one.? 11/21/2001

GSK representatives around the country also re?ected in their call notes

their use of sham consulting arrangements like SIBs to promote their products, including:

?Had good discussion with Dr. on all products. Wants to plan a ?shing
will research places and costs, and we?ll do it as a program or sib.?
5/30/01 Spencer, IN

certainly doesn?t like to be talked to about products. I need to be more

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sneaky. Such as the SIBS program.? 1/30/01 Bend, OR

?loved the sib. leaned a lot of new info about migraine and exercise. told me he

wrote two new imitrex scripts this week. It is all about the one hand washes the

other with this guy. I am totally ?ne with this because that is why we have a

3/16/01 Danvz'lle, 1N

?She has received her honorarium for the Pride program and she said she has used

a lot of WSR recently. uses it as add on and also in obese pts. Said SIB changed

her rx 12/4/01 Saxonburg, PA

?Gave him his SIB check. He said I made his day. I requested him to make my

days by giving me just 10% more pf his Imitrex Wellburtin prescriptions.?

11/16/01 Huntington, NY

?Spoke at SIB. did a fantastic job. Should see big 2/15/01 Hackensack, NJ

246. Not all doctors, however, were susceptible to this tactic. One representative
bemoaned: ?he is killing me, wont come to SIB, thinks of it as a bribe.? 4/16/01 Alton, 11.
B. GSK Paid Kickbacks Through CME and Other Sham Trainings

247. GSK also used so-called CME and CME Express programs and other sham
trainings for marketing purposes, and to promote off-label uses for the GSK prescription drugs.

248. For example, in or about 2000 and 2001, GSK used ?Reprint Mastery Training
Programs? or to further promote its drugs by purporting to pay physicians to train sales
representatives on clinical reprints. To do an RMT, a GSK representative set up ?training
sessions? with physicians to review reprints of studies. Although the training was purportedly
for the representatives, in fact, the sales force was already familiar with the materials. GSK
typically paid physicians $250 to $5 00 to review the reprints.

249. GSK representatives used these presentations to pay the physicians to review off-
label articles. For example, in the case of WB SR, reprint training covered such materials as the

Gadde weight loss study and a study of WBSR to treat sexual dysfunction.

250. Sales representatives also touted their use of these reprint programs to disseminate

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off?label information and induce doctors to prescribe, with comments such as:

?both sib and has increased his scripts, uses wellsr much more and anxiety is
not a 7/17/01 Union, NJ

with doc went over ADHD and weight loss data.? 8/27/01 Meruchen,
NJ

?Confirmation of wellsr check, planted seed with Madonna tickets that he is
probably getting 2, therefore needed more support? 7/16/01 Iselin, NJ

?reinforced everything we had done for him and we need his business now?
2/23/01

?gave him reprint check told him we need a good roi for our efforts and need him
to write our products exclusively agreed and said he would? 3/9/01 Orrvz'lle, OH

251. These CME programs purported to be independent education free of company
in?uence, but in fact functioned as GSK promotional programs disguised as medical education.
GSK maintained control and in?uence over the purportedly independent CME programs through
speaker selection, and in?uence over content and audience, among other things. Although third
party vendors were usually also involved, they served only as artificial ??rewalls? that did not I
insulate the program from in?uence.

252. GSK also used the ?speaker? payments for CME programs to reward physician
loyalty and induce increased prescriptions. Physicians trained at GSK ?speaker training?
programs often doubled as CME presenters, giving substantially the same presentation as they
did for the GSK speaking events. For example, Dr. Pradko?s standard lecture at GSK sponsored
talks was essentially the same presentation that he made at GSK?funded CME programs.

253. In or about 2001, GSK initiated a Express? program, funded by 
Marketing Department, which offered CME credits for attendance at GSK-sponsored events.
CME Express was not independent of in?uence. The content was often reviewed and

approved by GSK representatives. GSK sales representatives selected the speaker, chose the

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date and venue, and targeted potential attendees for invitation.

254. GSK used CME Express honoraria as a way to reward physicians and to induce
prescriptions. For example, a GSK representative noted that he would ?work on setting [a doctor
in Knoxville] up to speak for us possibly as CME express speaker on roundtable presentation to
his own group over lunch. may be the way to his business.? Another representative noted
about a doctor in Maryville, Tennessee: ?he wants money in his pocket. scheduled lunch. see if
he wants to do a wellbutrin orne express for his office.?

VII. THE FEDERAL HEALTH CARE PROGRAMS
A. The Medicaid Program

255. The Medicaid program is a joint federal?state program that provides health care
bene?ts for certain groups, primarily the poor and disabled. Each state administers a state
Medicaid program and receives funding from the federal government, known as federal ?nancial
participation, based upon a formula set forth in the federal Medicaid statute.

256. Before the beginning of each quarter, each state submits to CMS an estimate of its
Medicaid funding needs for the quarter. CMS reviews and adjusts the quarterly estimate as
necessary, and determines the amount of federal funding the state will be permitted to draw
I down as the state actually incurs expenditures during the quarter (for example, as provider claims
are presented for payment). After the end of each quarter, the state submits to CMS a final
expenditure report, which provides the basis for adjustment to quarterly federal funding.

257. The federal Medicaid statute sets forth the minimum requirements for state
Medicaid programs to qualify for federal funding. 42 U.S.C. 1396a. It also requires each
participating state to implement a plan containing certain specified minimum criteria for
coverage and payment of claims. 42 U.S.C. 1396b, 1396a(a)(l3), l396a(a)(30)(A).

258. While federal drug coverage is an optional bene?t available to the states, most

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states provide coverage for prescription drugs that meet the de?nition of a covered outpatient
drug, which is de?ned in the federal Medicaid Rebate Statute, 42 U.S.C. 

259. The Medicaid Rebate Statute generally prohibits federal payment for a covered 
outpatient drug unless the manufacturer enters into a rebate agreement with HHS. Once a
manufacturer has entered into a drug rebate agreement, a state is generally required to cover the
covered outpatient drugs of that manufacturer under the state plan unless ?the prescribed use is
not for a medically accepted indication.? 42 U.S.C. 

260. With certain limited exceptions not pertinent here, a prescription drug cannot be
distributed legally in interstate commerce without ?rst being approved by the FDA as safe and
effective for a particular use. To gain FDA approval for a particular use, data from adequate and
wellucontrolled clinical studies must demonstrate that the drug is safe and effective for the
proposed use. As part of the approval process, the FDA also must approve the drug?s labeling,
which sets forth detailed information about the drug, including the approved conditions of use,
dosages, and patient population(s). The drug?s manufacturer cannot lawfully distribute or cause
the distribution in interstate commerce of a drug that it intends to be used for an unapproved
purpose or in a manner inconsistent with the drug?s approved labeling, and cannot make or cause
to be made false or misleading claims about the drug.

261. The Medicaid Rebate Statute de?nes ?medically accepted indication? as any FDA
approved use or a use that is ?supported by one or more citations included or approved for
inclusion in any of the compendia? set forth in the statute Drugdex, American Hospital
Formulary Service, and US. Pharmacopeia?Drug Information). 42 U.S.C. 1396rm8(k)(6).

262. Thus, even if a drug is FDA-approved, Medicaid ordinarily does not cover off?
label uses of the drug that are not supported by one or more citations included or approved for

inclusion in the speci?ed compendia.

7l

263. The Federal Anti~kickback Statute, 42 U.S.C. l320a?7be) prohibits
any person or entity from offering, making, or accepting payment to induce or reward any person
for referring, recommending, or arranging for the purchase of any item for which payment may
be made in whole or in part by a federal health care program.

264. Medicaid does not cover claims for services or products where there has been a
kickback relating to the underlying transaction. Any provider who submits claims to Medicaid
must sign a provider agreement with each Medicaid program to which it submits claims.
Massachusetts regulations, for example, provide that: ?All pharmacies participating in
MassHealth must comply with the regulations governing Mas sHealth, including but not limited
to MassHealth regulations set forth in 130 CMR 406.000 and 450.000.? The Massachusetts
regulation at 130 CMR 450.261 provides: ?All members and providers must comply with all
federal and state laws and regulations prohibiting fraudulent acts and false reporting, specifically
including but not limited to 42 U.S.C. 1320a-7b [the federal anti?kickback statute].?

B. The Medicare Program

265. The Medicare program pays for the costs of certain healthcare services and items
for eligible beneficiaries based on age, disability or af?iction with end-stage renal disease.
Generally, no payments may be made under Medicare for expenses incurred for items and
services that are not ?reasonable and necessary? for the diagnosis and treatment of an illness. 42
U.S.C. l395y(a)(1)(A).

266. In 2003, Congress amended the relevant statutes to create Medicare Part D, which
provides additional optional drug coverage for Medicare bene?ciaries. Under the Part bene?t,
a ?covered part drug? means, in relevant part a drug that is approved by the FDA and is used
for a ?medically accepted indication.? 42 U.S.C. (citing 42

U.S.C. A medically accepted indication is defined as any use which is FDA-

72

approved or which is supported by one or more citations included or approved for inclusion in
one of three speci?ed drug compendia. Generally, Part coverage is provided by sponsors who
contract With CMS to provide such coverage and are responsible for making coverage
determinations in accordance with the statutes and regulations.

267. Medicare does not cover claims for drugs and/or physician services Where there
is a kickback involved in the underlying transaction. Claims submitted to federal health care
programs Where a kickback paid or accepted relating to the transaction are false under the FCA.

268. Providers that seek to bill Medicare must sign a Provider Agreement that states:

I agree to abide by the Medicare laws, regulations and program instructions that

apply to [me] . . . . I understand that payment of a claim by Medicare is

conditioned upon the claims and the underlying transaction complying with such
laws, regulations and program instructions (including, but not limited to Federal
anti?kickback statute and the Stark law), and on the [provider?s] compliance with

all applicable conditions of participation in Medicare.

C. False, Misleading and Illegal Marketing Caused the Submission of False and
Fraudulent Claims to Federal Health Care Programs

269. promotion of its drugs described above was both fraudulent and effective,
utilizing false and misleading statements and claims and kickbacks to cause doctors to prescribe
drugs and federal health care programs to pay millions of dollars in false and fraudulent
claims. Exhibit 39 is a sample of the claims submitted to federal health care programs for
reimbursement of Paxil for patients under 18. Exhibit 40 is a sample of claims for WBSR for
patients under 18 and for other off-label and non?medically accepted uses. Exhibit 41 is a
sample of the claims submitted to federal health care programs for reimbursement of Advair for
asthma patients who did not have a demonstrated need for Advair. These patients had no claims
for an ICS in the past year, no diagnosis code for COPD and no markers of moderate to severe
asthma i.e. no asthma?related hospital or ER visits in the previous month and either A) only 1 or
2 claims for SABA in the past year or B) no prior asthma medications in the past year. Exhibit

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42 is a sample of claims submitted to federal health care programs for reimbursement of Advair
for patients who did not even have a diagnosis of asthma or COPD. Through the false and
misleading marketing schemes and kickbacks detailed herein, GSK caused these drugs to be
prescribed for these uses.

270. Through payment of kickbacks described above to prescribers of WBSR, Advair
and Paxil, GSK also caused the claims to federal health care programs for reimbursement of the
GSK drugs subsequently written by those prescribers and for the prescribers? services connected
with the selection of the GSK drugs to be false and fraudulent claims.

COUNT I: FALSE CLAIMS ACT (PRESENTMENT OF FALSE CLAIMS)

271. The United States hereby incorporates by reference the documents and exhibits
attached, recited or referenced in the Relators? Complaints in these four consolidated matters.

272. The United States realleges the preceding paragraphs as if fully set forth herein.

273. false and fraudulent statements, including with respect to the safety and
ef?cacy, superiority, and medical necessity and appropriateness of its drugs, to the public, to
patients, to physicians and directly to Medicaid and other federal health care programs, were
material to the physician?s decisions to prescribe these drugs and the United States? decision to
pay claims for these drugs and related services.

274. GSK knowingly caused to be presented false or fraudulent claims for payment or
approval to the United States in violation of 31 U.S.C. 3729(a)(1)(A), including

claims for drugs caused by illegal promotion of its products as set forth
above, samples of which are set forth in Exhs. 40?43; and

claims for physician services by physicians who had received the improper
inducements from GSK alleged above.

275. By virtue of the false or fraudulent claims that GSK caused to be made, the

United States suffered damages in an amount to be determined at trial.

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COUNT II: FALSE CLAIMS ACT (FALSE STATEMENTS)
276. The United States realleges the preceding paragraphs as if fully set forth herein.
277. As set forth above, GSK knowingly made and caused to be made or used false
and/or fraudulent statements or records material to false and/or fraudulent claims and/or to get
these claims paid or approved by the United States, in violation of 31 U.S.C. 3729(a)(1)(B) and
former 31 U.S.C. 3729(a)(2)1, including 

claims for drugs caused by illegal promotion of its products as set forth
above, samples of which are set forth in Eth. 40-43;

claims for physician services by physicians who had received the improper
inducements from GSK alleged above.

278. By reason of these payments, the United States has been damaged in an amount to

be determined at trial.
COUNT UNJU ST 

279. The United States realleges the preceding paragraphs as if fully set forth herein.

280. As a consequence of the acts set forth above, GSK was unjustly enriched and
received illegal pro?ts. The United States conferred bene?ts upon GSK, GSK knew of and
appreciated these bene?ts, and retention of these bene?ts under the circumstances would
be unjust as a result of its conduct.

281. The United States therefore claims the recovery of all monies by which GSK has

been unjustly enriched and has illegally pro?ted, in an amount to be determined, which in equity

 

1 The Fraud Enforcement and Recovely Act of 2009 Pub. L. No. 111-21, 123 Stat. 1617 (May
20, 2009), modi?ed and renumbered the subsections of 31 U.S.C. 3729(a) of the False Claims Act, "to re?ect the
original intent of the law." Id. 4, 123 Stat. 1621. Among other things, FERA modi?ed former section 3729(a)(2)
to impose civil liability on any person who "knowingly makes, uses, or causes to be made or used, a false record or
statement material to a false or fraudulent claim.? Id. (recodifying section 3729(a)(2) as Although
FERA generally applies only to conduct occurring on or after the date of its enactment, Congress speci?ed that
Section 37 "shall take effect as if enacted on June 7, 2008, and apply to all claims under the False Claims
Act. . . that are pending on or after that date.? 123 Stat. 1625.

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should be paid to the United States.
PRAYER FOR RELIEF
WHEREFORE, the United States seeks against GSK the following:
1. On Counts One and Two under the False Claims Act, the amount of the United
States? damages, trebled as required by law, and such civil penalties as are required by law,
together with all such further relief as may be just and proper.
2. 011 Count Three for unjust enrichment/disgorgement, the damages sustained

and/or amounts by which GSK was unjustly enriched or obtained illegally, plus interest, costs

3

and expenses, and all such further relief as may be just and proper.
DEMAND FOR JURY TRIAL
The United States demands a jury trial in this case.
Respectfully submitted,

TONY WEST
ASSISTANT ATTORNEY GENERAL

CARMEN M. ORTIZ

UNITED STATES, TTORNEX

 If? 11:457. (is  3350/1
SARA MIRON 1

Assistant United States Attorney

United States Attorney?s Office

1 Courthouse Way, Suite 9200

Boston, MA 02210

(617) 748-3366

 
  

Dated: October 26, 2011 .

JOYCE R. BRANDA

JAMIE ANN YAVELBERG
ANDY . MAO

DOUGLAS J. ROSENTHAL
Attorneys, Civil Division

United States Department of Justice
PO. Box 261, Ben Franklin Station
Washington, DC. 20044

(202) 6160539

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