Quellen:

//www.boocompany.com/index.cfm/content/story/id/14638/


Eli Lilly: Für ein paar Milliarden Dollar mehr
INSIDER Eli Lilly von hockeystick
09:45 Donnerstag, 15. Februar 2007

Der Pharmakonzern Lilly hat offenbar jahrelang potentiell tödliche Nebenwirkungen des Medikaments Zyprexa verharmlost, um die Milliardenumsätze mit dem Präparat nicht zu gefährden. Brisante interne Dokumente scheinen dies zu belegen. Um zu verhindern, dass diese im Rahmen eines Gerichtsverfahrens an die Öffentlichkeit gelangen, hat Lilly bislang in mehr als 28.000 Fällen außergerichtliche Entschädigungszahlungen von insgesamt 1,2 Milliarden Dollar geleistet. Die Katze ist dennoch aus dem Sack. BooCompany bietet ab sofort 5.506 Seiten belastende Original-Unterlagen zum Download an und gewährt so nie dagewesene Einblicke in die Abgründe des Pharmamarketings.


Die interne Auswertung von Studien durch Lilly hatte bereits 1999 ergeben, dass bei einem erheblichen Teil der Anwender von Zyprexa das Körpergewicht in einem zum Teil grotesken Ausmaß zunimmt. Weiterhin lag eine Studie vor, in der sich die Häufigkeit von Hyperglykämien (Überzuckerungen) unter Zyprexa mehr als verdreifacht hatte, und es gab zahlreiche Fallberichte, nach denen das Medikament Diabeteserkrankungen induziert. Aus Sorge um den Markterfolg von Zyprexa wurden diese Risiken von Lilly in der öffentlichen Darstellung systematisch herunterspielt. Aus den vorliegenden Unterlagen ist im Detail nachvollziehbar, wie die Pharmareferenten mit Hilfe sogenannter "Message Algorithms" darauf gedrillt wurden, mögliche bereits vorhandene Bedenken der Ärzte ohne Entgleisung der Gesichtszüge systematisch zu zerstreuen (No "Flinch Factor"). Unbedingt zu vermeiden galt es, Nebenwirkungen wie die Gewichtszunahme von sich aus anzusprechen (Don't introduce the issue!!!).

Das zweite Problem von Lilly im Zusammenhang mit Zyprexa ist die gezielte Vermarktung des Präparats für Indikationen, für die es nicht zugelassen war. Als Zielsegment identifiziert wurde beispielsweise "Martha", der von den Lilly-Marketingstrategen erdachte Prototyp einer betagten und leicht demenzkranken Witwe. Für das Marktsegment "Martha" erkannten die Strategen ein erhebliches Umsatzpotential. Da störte es dann auch kaum, dass Zyprexa gegen Demenz weder wirkt noch zugelassen ist, ja sogar gerade in dieser Altersgruppe zu besonders vielen Todesfällen führt. Ebenso wenig ließ man sich dadurch bremsen, dass dieses sogenannte "off-label marketing" ausdrücklich verboten ist. Eigens für Martha und weitere Patientenprofile, die ebensowenig im Wartezimmer psychiatrischer Praxen anzutreffen sind, wurde im Jahr 2000 die Vertriebsoffensive "Viva Zyprexa!" gestartet, die sich (für Psychopharmaka ungewöhnlich) an die Zielgruppe der Hausärzte richtet.

Der Name der Viva-Zyprexa-Kampagne lehnt sich offenbar an den Elvis-Titel "Viva Las Vegas!" an, der von den Lilly-Verantwortlichen zur Steigerung der Motivation der Pharmareferenten sogar mit einem neuen Text ausgestattet (pdf, S. 67) wurde. (Wem die Originalität dieser Idee entgangen sein sollte: Elvis starb als stark übergewichtiger, tablettenabhängiger Diabetiker im Alter von 42 Jahren.)

Nach Ansicht von Beobachtern gehören die Vorgänge rund um Zyprexa nicht nur wegen der hohen Opferzahl zu den schwerwiegendsten Pharma-Skandalen der vergangenen Jahrzehnte. Auf die Frage, ob es sich bei Zyprexa um das "nächste Vioxx" handeln könnte, zitierte der angesehene Epidemologie-Professor Curt Furberg einen mit solchen Fällen vertrauten Anwalt kürzlich mit den Worten: "This is worse than all else I have seen, there is no chance that the company can let this go to court, then everything is made public. They have to settle the case."

Auf verschlungenen Wegen ist Ende vergangenen Jahres trotz aller Geheimhaltungsbemühungen von Lilly ein umfangreiches Paket mit belastenden Dokumenten in die Hände eines Reporters der New York Times gelangt, der daraus im Dezember eine Serie von Titelgeschichten gemacht hat. Schlimmer noch, über das TOR-Netzwerk sind etwa zur gleichen Zeit Scans der Dokumente in die Weiten des Internets gesickert, zunächst in Form eines Pakets mit eher sperrigen TIFF-Dateien.

Als besonderen Service stellt BooCompany interessierten Lesern die Dokumente ab sofort im PDF-Format zur Verfügung. Erstmals liegt auch eine Textversion (.TXT) der Unterlagen vor, die für BooCompany von 631 chinesischen Datentypisten in 3.500 Arbeitsstunden abgeti aus den gescannten Dokumenten mittels automatischer Texterkennung erzeugt wurde. Die einzelnen PDF-Dateien befinden sich in diesem Verzeichnis, die TXT-Dateien sind in diesem Verzeichnisbaum untergebracht. Wer sich näher mit den Freuden des Pharmamarketings beschäftigen möchte oder wer dem Berufsstand des Pharmareferenten auch nur noch einen Funken Respekt entgegenbringt, dem sei der Download des komprimierten Gesamtpakets als ZIP-Datei (ca. 280 MB) angeraten. Wer schon auf anderen Wegen an die PDF-Dokumente gelangt ist, für den gibt es hier den eingepackten TXT-Verzeichnisbaum auch einzeln als ZIP-Datei (ca. 7,5 MB). Die Textversion erweist sich beim Stöbern in den Dokumenten im Zusammenspiel mit Programmen wie "Windows Desktop Search" oder "Google Desktop Search" als überaus hilfreich.

Eine Zusammenfassung der Hintergründe des Zyprexa-Skandals gibt es bei Strappato, aktuelle Entwicklungen zum Thema finden sich auf dem gleichen Blog unter diesem Link.


//gesundheit.blogger.de/stories/682391/

Eli Lilly/Zyprexa® case - Ein Überblick

Die deutschen Medien haben in dem Fall bisher kaum berichtet. Daher halte ich es für sinnvoll, erst einmal das Geschehen zusammenzufassen.
Eli Lilly and Company (kurz: Lilly)
1876 gründete Colonel Eli Lilly in Indianapolis das Unternehmen Eli Lilly.
Lilly gehört mit einem Umsatz von $ 14,6 Mrd. (2005) zu den weltweit zehn grössten Pharmaunternehmen. Bekannteste Produkte: Prozak© (Fluoxetin in Deutschland: Fluctin®) und Cialis® (Tadalafil). Indianapolis ist "Lilly-City". Der Konzern ist allgegenwärtig - wie BASF in Ludwigshafen zu seinen besten Zeiten. "Lilly Endowment" eine der weltgrössten gemeinnützigen Stiftungen besitzt 13% der Aktien.

Interessant ist die gute connection zur Bush-Familie: Nachdem George H.W. Bush 1977 als CIA-Direktor abgetreten ist, wurde er Mitglied im Board of Directors bei Eli Lilly. Der Vater seines späteren Vize-Präsidenten Dan Quayle kontrollierte das Unternehmen und die Zeitung Indianapolis Star. Als US Vize-Präsident und später als Präsident war Bush oberster Lobbyist für Lilly und die Pharmaindustrie. Die Bush-Familie investierte über Jahre in Lilly-Aktien. Auch andere Mitglieder der konservativen US-Regierung waren oder sind mit Lilly verbunden: Der frühere US-Verteidigungsminisiter  Donald Rumsfeld als Ex-Board Mitglied, wie auch der frühere Budget-Direktor im White House,  Mitch Daniels, ein ehemaliger Lilly Vice-President, der seit 2004 Governor von Indiana ist. Sidney Taurel, CEO von Lilly, war Beiratsmitglied im Heimatschutzministerium (U.S. Department of Homeland Security).
Zyprexa® ( Olanzapin) Zyprexa® ist Lillys Hauptprodukt und trägt über 30% zum Umsatz bei. Es ist zugelassen zur Therapie von Bipolaren Störungen, Schizophrenie und akuter Manie. In Deutschland lag Zyprexa® im Jahr 2005 an 119. Stelle der meistverordneten Medikamente mit 853.400 Verordnungen und einem Umsatz von fast 192 Millionen Euro (Quelle: Arzneiverordnungsreport 2006). Damit entfallen über 10% der Auslandsumsätze mit diesem Medikament auf Deutschland.  Die Zyprexa-Umsätze lagen 2006 weltweit bei $ 4,36 Milliarden.

In der Öffentlichkeit tauchten 2002 erste Meldungen von einer mögliche Induktion von Diabeteserkrankungen durch Olanzapin auf. Viele Erkrankungen gingen mit einer Ketoazidose einher, es kam zu nekrotisierenden Pankreatitiden und 23 Patienten starben, darunter ein 15-jähriger Jugendlicher. Seither gab es eine Reihe von Fall-Kontroll-Studien, die den Zusammenhang festigten, jedoch nicht nur für Olanzapin, sondern auch für eine Reihe weiterer Antipsychotika. Weshalb die amerikanische Zulassungsbehörde FDA seit Ende 2003 vor einem Hyperglykämie-Risiko bestimmter Antipsychotika warnt. Vorher stuften die Fachinformationen Diabeteserkrankungen als seltene Komplikation ein.


Zyprexa®/Eli Lilly case
Im Dezember 2006 veröffentlichte der Journalist Alex Berenson in der New York Times einige Artikel, die belegen, dass Lilly schon vor 2002 von dem erhöhten Risiko der Gewichtszunahme, Hyperglykämie und Diabetes bei der Einnahme von Zyprexa® wusste. Lilly hatte dies gegenüber Patienten, Ärzten und der FDA verschwiegen und verharmlost. Berenson hat ausserdem beschrieben, wie Lilly Zyprexa® für nicht zugelassene Indikationen vermarktet, ein sogenannter "off-label use". Eine besondere Brisanz liegt darin, dass Lilly in den letzten Jahren immer wieder mit Klagen konfrontiert war, in denen tausende Patienten auf Entschädigung klagten und die aussergerichtlich durch Zahlungen von $ 1,2 Milliarden beigelegt worden sind. Lilly hatte es erreicht, dass die Dokumente, die Gegenstand des Verfahrens waren, nicht veröffentlicht werden und hat dies mit Unternehmensgeheimnissen begründet.

Ein paar links zur den NY Times Artikeln: hier, hier oder hier.

Bei seinen Artikeln stützte Berenson sich auf die internen Dokumente von Lilly. Wie kam er daran? Dr. David Egilman, als Gutachter/Experte bei den Prozessen dabei, übergab sie Jim Gottstein, einem Anwalt aus Alaska, der diese an Alex Berenson weiterreichte. Beide wollten damit die Öffentlichkeit über die Zyprexa®-Risiken warnen und mögliche weitere Schäden für die Patienten verhindern. Primäres Ziel war den Umfang des off-label Marketings offenzulegen, da der nicht zugelassene und nicht durch klinische Studien auf Sicherheit und Wirkung geprüfte Einsatz des Medikaments ein ethisch nicht zu vertretendes Risiko für die Patienten darstellt. Dass die Therapie mit Zyprexa® mit dem Risiko der Gewichtszunahme und Hyperglykämie verbunden ist, war früh diskutiert worden und die meisten Klagen, die jetzt außergerichtlich beglichen wurden, stammen aus der Zeit vor der Änderung der Fachinformation Ende 2003. Neu war das Ausmass der Verharmlosung dieser Risiken und der interne Umgang damit, die durch die Dokumente ans Licht der Öffentlichkeit gelangten.

Die Dokumente stiessen auf grosses Medieninteresse in den USA. Auch als aus den Dokumenten zitiert wurde, leugnete Lilly jegliche Schuld. Am 15. Januar 2007 gaben die Lilly-Anwälte an, dass die Dokumente keine weite Verbreitung haben:
Despite a concerted effort by a small group of individuals to take advantage of Dr. Egilman's and Mr. Gottstein's violation of CMO-3, and to violate the Temporary Mandatory Injunctions, this effort fell flat.
Zu diesem Zeitpunkt konnte sich jedoch jeder die "ZyprexaKills memos", als "ZyprexaKills.tar.gz"  aus dem Internet besorgen.
Informationsfreiheit und Bürgerrechte
Im Dezember hatte der Richter Jack B. Weinstein in Brooklyn, N.Y. verfügt, dass Gottstein die Namen der Empfänger der Zyprexakills memos herausgibt und die Dokumente wieder einsammelt. Wieder ein Beispiel, dass Konzerne die Macht des Internets unterschätzen. Denn die Dokumente waren längst im Netz und eine anonymer Nutzer, im Verfahren "John Doe" genannt, setzte in einem öffentlichen wiki - Zyprexa Kills //zyprexa.pbwiki.com - einen link zu diesen Dateien. Ein Lilly-Anwalt verlangte am 29. Dezember eine Löschung des links mit Verweis auf den Gerichtsbeschluss, der aber das wiki nicht speziell mit einschloss. Daraufhin forderte Richter Weinstein am 4. Januar verschiedene Organisationen und Internetnutzer auf, ihre links zu den ZyprexaKills-Dateien zu löschen und die "facilitat[ing] dissemination" zu stoppen.

Doe kam dem nach, ist aber der Überzeugung, dass der Zugang zu den Dateien wichtig und nötig ist, damit die Öffentlichkeit die medizinischen, ethischen und gesundheitlichen Aspekte bezüglich Zyprexa® versteht. Die  EFF hat sich dem Fall angenommen und scheut sich nicht das Wort "Zensur" zu verwenden:
Eli Lilly's efforts to censor these documents off the Internet are particularly outrageous in light of the information reported by The New York Times, which suggests that doctors and patients who use Zyprexa need to know the information contained in these documents.

Richter Weinstein hat Alex Berenson eingeladen (nicht vorgeladen!), und hofft, dass er von dem Journalist mehr über die Hintergründe rund um die Weitergabe der Dokumente erfährt. Ein investigativer Top-Journalist soll über seine Methoden und Informanten plaudern. Sehr bizarr und klingt ein wenig hilflos.

Das Gericht hat entschieden, dass die vertraulichen Dokumente über das Marketing von Zyprexa von David Egilman und Gottstein an Lilly zurückgegeben werden müssen. Der NY Times Journalist, der die Dokumente von den beiden erhalten hat, ist nicht von der Entscheidung betrofffen, genauso wie die Quellen im Internet, wo sie als "ZiprexaKills memos" zu finden sind. In Zukunft könnte damit die Verbreitung solcher als firmenintern klassifizierten Dokumente unterbunden werden.

Damit ist der Fall in den USA auch zu einer Frage der Informationsfreiheit geworden.

--
Die ZyprexaKills memos können bei boocompany.com im pdf- und txt-Format runtergeladen werden.

Alle Artikel zum Zyprexa-Skandal hier im blog: //gesundheit.blogger.de/topics/Zyprexa

Conflict of interest
Der Autor war vor einigen Jahren für Eli Lilly an der Erstellung eines Gutachtens zum Thema "Bipolare Störungen" beteiligt.

[Zyprexa]
    strappato   2007-02-01   Link   (7 Kommentare)  Ihr Kommentar


hockeystick   2007-02-01
OCR ist durchaus eine nützliches Hilfsmittel. Das kann dann z.B. so aussehen (vgl. ZY1 00008867, S. 3):

.....
11/30/99 06:26 PM
....
Subject: Interim body weights in 6-Mo PLGA Study
I thought you might find the attached graphs interesting. This is only through 75 days (less than halt way). Although the effect is not statistically significant by Dunnetts at each time point, the visual trend seems compelling.
Standard deviations are around 10% of the absolute body weights.
Bob


strappato   2007-02-01
Ja, habe ich auch mit einigen Dateien gemacht, aber mein altes OCR Programm lässt sich nicht automatisieren: Datei holen - umwandeln - als Textdatei wegschreiben.

Mal was zum Text oben: Habe ich was vergessen? Ich hoffe ja auf ein paar Kommentare.


hockeystick   2007-02-02
Da gibt es einen Teckie, der da was in der Mache hat, wie man hört. Rund 5500 Seiten in ASCII.

Die juristischen Verwicklungen rund um die Dokumente sind ziemlich kompliziert, vgl. z.B.

//lawprofessors.typepad.com/tortsprof/2007/01/zyprexa_well_wh.html
//lawprofessors.typepad.com/tortsprof/2007/01/highlights_from.html

Overall, my view is about the same as it was: Egilman has significant potential trouble. Gottstein has somewhat less. And the third-party distributors have a real solid argument that they should not be enjoined, since there's minimal evidence other than extremely coincidental timing that the documents they distributed came from the violation of the protective order.

Grisham kann da einpacken.

Interessant auch noch, dass das Gericht bereit ist, in den nächsten Tagen erneut über die öffentliche Freigabe der Dokumente zu entscheiden.


strappato   2007-02-02
Ich halte das auch für höchst spannend und wichtig. Nur habe ich das Gefühl das in Deutschland sich nur Insider dafür interessieren. Aber jeden Pups über die Gesundheitsreform ausbreiten, das können die Medien.


hockeystick   2007-02-02
Man muss da nur blind reingreifen, und mir kommt die Galle hoch:

Critical success factors for appropriately dealing with the hyperglycemia/diabetes objection:
(1) Have a good understanding of hyperglyoemia/diabetes.
(2) Focus your sales presentation on the outstanding efficacy of ZYPREXA and frame hyperglyoemia in the context of the overall safety profile and tie to risks/benefits.
(3) Understand how and When to properly use the hyperglyoemia Data on Demand sheet and the insert comparison chart (See "Targeting)? section and "Message Algorithm?).
(4) Be sure to use the appropriate tone with physicians - confident, positive and non-defensive.
(5) Address the question; "How can you have comparable rates of
hyperglyoemia/diabetes if there is more Weight gain With ZYPREXA in some patients?') (See Q & A section for answer).
We hope this Resource Guide and the new Hyperglyoemia Sell Sheet give you What you need to knowledgeably and confidently handle these objeotions. Remember that effectively handling hyperglyoemia and diabetes concerns is a Win-Win situation:
Neutralizing these concerns with just a few key oustomers could provide the promise of ZYPREXA to more patients and at the same time put more money in your pocket! We appreciate your dedication and expertise. We are counting on those attributes as We move forward. Best of luck, and good selling.

For your information only.
Not for use in detailing.
Zyprexa MDL 1596: Contidential-Subject to Protective Order
ZY202417650
Zyprexa MDL Plaintiffs' Exhibit No.O9506 Page 13


Die Pharmaindustrie und die Pharmareferenten stehen da mit der Hose bis zu den Knöcheln runtergelassen, und das was man sieht, ist wahrlich kein schöner Anblick.


hockeystick   2007-02-02
Hübsch z.B. auch die folgende Folie (soviel zum beratenden Charakter der Tätigkeit von "Pharmaberatern"):

Weight Gain Management

- Don't introduce the issue!!!
- Maintain focus on main message. Primary objective is to effectively control all symptoms of psychoses and reintegrate the patient.

European Planners Meeting

(Hintergrund: Ein paar Folien weiter vorne ist zu lesen, dass in einer Studie 28 Prozent der Patienten nach einem Jahr bereits mehr als 10kg zugenommen hatten.)

Die drei Ausrufezeichen sind auch so auf der Folie (ZY1 00040198, S.20). Die Dokumente mit drei Ausrufezeichen in Folge sind generell interessant.


Kommentieren



hockeystick   2007-02-13
"There is no chance that the company can let this go to court, then everything is made public"
Hier noch eine interessante Zusammenfassung der Vorgänge aus dem Arzneitelegramm 1/2007, mit Hinweisen auf mögliche weitere Nebenwirkungen von Zyprexa:

Olanzapin (ZYPREXA) – Risikodaten unterdrückt:
Unterdrückung von Negativdaten (a-t 2005; 36: 1-
2) behindert die objektive Information zu Nutzen und Schaden
von Arzneimitteln. Die New York Times berichtet aktuell
über interne Unterlagen der Firma Eli Lilly, nach denen diese
ihr bekannte Risiken des Neuroleptikums bewusst verharmlost
hat. Bereits 1999 wertete demnach der damalige wissenschaftliche
Leiter Gewichtszunahme und Hyperglykämie (s.
a-t 1998 Nr. 1: 11) als Gefahr für den ökonomischen Langzeiterfolg
des für die Firma wichtigen Produktes. Die Auswertung
von Studien hatte ergeben, dass 16% der Anwender
von Olanzapin mehr als 30 kg zunehmen. Nach anderen internen
Daten erhöht sich bei 30% der Patienten das Gewicht
pro Jahr um mehr als 10 kg. Zudem sei eine Inzidenz von
Hyperglykämien unter Olanzapin von 3,6% versus 1,05%
unter Plazebo für Gespräche mit Ärzten und für die US-amerikanische
Arzneimittelbehörde FDA auf 3,1% vs. 2,5% „revidiert”
worden (New York Times, 17., 20. und 21. Dez.
2006). In der Fachinformation werden im Abschnitt „Warnhinweise”
Hyperglykämie oder Entwicklung oder Verschlechterung
eines Diabetes nach wie vor als „sehr seltene” Störwirkungen
(unter 0,01%) bezeichnet (Lilly: Fachinformation
ZYPREXA, Stand Sept. 2006). Obwohl die Firma 28.500
Patienten, die wegen Diabetes oder anderer Störwirkungen
unter Olanzapin geklagt hatten, mit insgesamt 1,2 Milliarden
Dollar entschädigt, verbreitet sie weiterhin, dass es keine Evidenz
dafür gäbe, dass Olanzapin Diabetes verursache (New
York Times, 8. Jan. 2007). Ein Experte, der in einem Gerichtsverfahren
Einsicht in Eli Lillys Unterlagen zu Olanzapin
hatte, betont, dass die gefährlichsten Effekte von ZYPREXA
der Öffentlichkeit und den verschreibenden Ärzten vorenthalten
würden. Auch der FDA wirft er Unterdrückung von Negativdaten
zu Olanzapin vor. Die Behörde weigere sich bis
heute, Ergebnisse zu Suizidversuchen aus Studien vor der
Marktzulassung offenzulegen (FURBERG, C.: //www.icspp.org/index.php?option=com_content&task=view&id=135&Itemid=70 ). Dies wurde schon 2002 von einem
Kritiker der Pharmaindustrie bemängelt. Seines Wissens liegt
die Todesrate unter Olanzapin in den von Eli Lilly der FDA
übermittelten Studiendaten höher als unter jedem anderen
Neuroleptikum (HEALY, D.: //www.ahrp.org/ethical/HealyResponseToPfizer.pdf ). Auch eine amerikanische Expertin
vermisst im FDA-Gutachten Angaben zu Suizidversuchen, obwohl 12 von 20 Todesfällen bei 3.139 Olanzapinanwendern
durch Suizide bedingt sind (JACKSON, G.E.:
//psychrights.org/states/Alaska/CaseOne/30-Day/ExhibitD-Olanzapine.htm ). Vergleichsdaten gibt es aus einer zweijährigen
Studie mit knapp 1.000 schizophrenen oder schizoaffektiven
Patienten mit hohem Suizidrisiko: Unter Clozapin
(LEPONEX u.a.) treten signifikant weniger kombiniert ausgewertete
Suizide, Suizidversuche oder Hospitalisierungen
wegen Suizidalität auf als unter Olanzapin (Hazard Ratio:
0,76, 95% Konfidenzintervall 0,58-0,97; MELTZER, H.Y.
et al.: Arch. Gen. Psychiatry 2003; 60: 82-91).

Aus dem Furberg-Interview (Link im Text):

A court case with Zyprexa was on its way and I became involved, had the opportunity to take part of the information and talked to a lawyer. He, who had experience from similar cases, told that "this is worse than all else I have seen, there is no chance that the company can let this go to court, then everything is made public.
They have to settle the case."

(Bemerkenswert und eindrucksvoll, dass das a-t bereits im Januar 1998 anhand eines Fallberichts über das mögliche Diabetes-Risiko von Zyprexa berichtet hatte.)



//clinpsyc.blogspot.com/2007/02/zyprexa-off-label-promotion.html


Friday, February 16, 2007
Zyprexa: Off-Label Promotion?
The document discussed in this post is called the “Zyprexa Primary Care Presentation”. It appears to be a transcript of a speech Mike Bandick, the Zyprexa Brand Manager, gave at the Eli Lilly National Sales Meeting on March 13, 2001.
It is important to note that Zyprexa is only FDA-approved for use in schizophrenia and bipolar disorder. The document appears to indicate that Bandick was encouraging salespeople to market Zyprexa for treating more than just these two conditions.

Bandick said:

We intend, quite simply, to redefine the way PCPs treat mood, thought and behavioral disturbances. We will continue to focus on symptoms and behaviors that PCPs see every day.
Later he said, referencing Zyprexa:
Broad symptom efficacy in mood, thought, and behavioral disturbances.
It seems curious that Lilly states they did not market Zyprexa for off-label purposes, yet the term “Mood, thought, and behavioral disturbances” seems a fair amount broader than schizophrenia and bipolar disorder. In addition, schizophrenia and bipolar disorder (especially bipolar I, which is the much more severe form of bipolar in comparison to bipolar II) are uncommon disorders. It is highly unlikely that primary care physicians would see patients with such conditions “every day.” However, it is certainly possible that a PCP may run across individuals who are manifesting much less severe “disturbances”, and it may well have been that it was this group, the patients who exhibited mild “mood, thought, or behavioral” symptoms, for whom Zyprexa was being marketed.
Bandick went on to discuss the case of Martha, which was discussed as being a case that seemed to much more strongly resemble dementia than schizophrenia or bipolar disorder. Martha was a hypothetical case that reps were said to have used in order to sell the benefits of Zyprexa to physicians. Bandick said:
Let me take a quick time out and make one quick comment on Martha. What’s the first thing you notice about Martha? She’s old! That does two things. First, it reinforces Zyprexa as a nursing home drug. Our mission is to build a primary care franchise, and let our long-term care team drive the nursing home business. Second, it limits the perception of behavioral disturbances – agitation, tension, anger, hostility all show up in primary care in a variety of packages. When you describe Martha, make her symptoms more prominent than her age.
It is certainly possible that there was a push to get PCP’s to recognize “agitation, tension, anger, [and] hostility” in their patients in a “variety of packages,” which could well mean off-label; the vast majority of people who struggle with these particular issues have neither schizophrenia nor bipolar disorder. At this point, I have not seen enough about the “long-term care team” to offer any intelligent idea as to their strategy, though I would assume that Martha may have been involved.

A few pages later, Bandick stated:

Emphasize patient benefits. And know the difference between a competitor and a “companion.” Drugs like Aricept and Zoloft belong to what we’re calling companion classes, drugs we augment rather than replace.
Aricept (donepezil) is FDA approved in the treatment of Alzheimer’s Disease, and Zoloft is approved in the treatment of depression and some anxiety disorders. Aricept is very rarely used in the treatment of schizophrenia, and Zoloft is not a sensible treatment for symptoms of either schizophrenia or bipolar disorder.

The idea to prescribe Zyprexa along with Aricept seems related to the case of Martha, who, as stated earlier, was a hypothetical patient discussed in sales materials, whose symptoms appear to resemble dementia (for which Aricept is frequently used) as opposed to schizophrenia or bipolar. Bandick’s speech lends credibility to the idea that Zyprexa was to be sold as an add-on for dementia treatment.

Also note that later in the same document, Bandick states that:
We expect approval this summer of an intramuscular formulation which will add two crucial words to our label: agitation and dementia.
It seems Lilly expected Zyprexa would be approved for dementia. Thus, it is possible that they were getting the word out early on Zyprexa for dementia, which would have not been allowable per FDA marketing regulations, although the approval never occurred.

Doctor-to-Doctor Marketing: Outside of sales reps, drug companies frequently use other practicing and/or academic physicians to help market their products. This is known as peer-to-peer marketing. In the current document, Bandick is quoted as saying:

Regarding peer-to-peer, we’ve just completed the second of two speaker training programs and have unleashed more than 130 psychs and PCP’s who are chomping at the bit to help you sell Zyprexa.
Bandick also stated:

We must utilize trained speaker to educate PCPs – not only on Geodon’s [a competitor medication] drawbacks, but especially on Zyprexa’s advantages and benefits to patients.
There is very likely nothing illegal about this practice, but having practicing and/or academic physicians act as salespeople can certainly raise conflicts of interest. While physicians may be more apt to believe other physicians as opposed to a sales rep, the line between sales rep and peer physician blurs significantly when physicians are paid and trained by a sponsoring company such as Lilly.

The document from which all quotes are cited is: Zy100041630.pdf and I thank Furious Seasons for hosting it as well as the other Zyprexa documents. Additional thanks to Alex Berenson of the New York Times, who first discussed Martha in an earlier article.
Labels: marketing, Zyprexa
POSTED BY CL PSYCH AT 2/16/2007 08:14:00 PM






//www.nytimes.com/2006/12/21/business/21drug.html?ex=1324357200&en=4821a4f0b2ca1add&ei=5090&partner=rssuserland&emc=rss


Disparity Emerges in Lilly Data on Schizophrenia Drug


By ALEX BERENSON
Published: December 21, 2006
For at least a year, Eli Lilly provided information to doctors about the blood-sugar risks of its drug Zyprexa that did not match data that the company circulated internally when it first reviewed its clinical trial results, according to company documents.
The original results showed that patients on Zyprexa, Lilly’s pill for schizophrenia, were 3.5 times as likely to experience high blood sugar levels as those taking a placebo, according to a February 2000 memo sent to top Lilly scientists. The memo is one of hundreds of internal Lilly documents provided to The New York Times by a lawyer in Alaska who represents mentally ill patients.
But the results that Lilly eventually provided to doctors until at least late 2001 were very different. Those results indicated that patients taking Zyprexa were only slightly more likely to suffer high blood sugar as those taking a placebo, or an inactive pill.
Another Lilly report, from November 1999, shows that Lilly found after examining 70 clinical trials that 16 percent of patients taking Zyprexa for a year gained more than 66 pounds.
The company did not publicly disclose that figure, instead focusing on data from a smaller group of clinical trials that showed about 30 percent of patients gained 22 pounds.
Weight gain and high blood sugar are important risk factors for diabetes, and the question of whether Zyprexa causes diabetes has been a subject of scientific debate for several years.
Lilly says no link has ever been proven.
In response to questions about the difference between its first view of the data and its subsequent public description, Lilly issued a statement yesterday saying that the later figures were accurate and the information in February 2000 was out of context.
In yesterday’s statement, the company said that after the February 2000 memo, it re-examined its clinical trial results and found errors in its “final, standard quality check of the data.”
But the February 2000 document, which is labeled “Confidential,” does not indicate that the figures it contains are preliminary. In fact, in a footnote, it explains that the data exclude patients “from whom there was a probable lab error.”
A separate document from November 1999 includes handwritten figures identical to those from the February document, with additional detail about the increases in blood sugar that patients suffered.
The revised figures were shared with the Food and Drug Administration, Lilly said. It did not say whether it had ever disclosed the initial data to the F.D.A.
The F.D.A. did not respond to requests for comment yesterday.
The 2000 memo indicates that it was prepared as Lilly considered changing Zyprexa’s prescription label to provide doctors with more information about the drug’s potential to raise blood-sugar levels.
The issue was crucially important to the sales prospects of Zyprexa, which was introduced in 1996. Psychiatrists were already increasingly aware by 2000 that Zyprexa caused severe weight gain in many patients.
“In 1999, we already were thinking this drug causes weight gain — that’s clear — and there could be a lot of other metabolic consequences of that,” Dr. David N. Osser, a psychiatry professor at Harvard University, said yesterday. “The weight gain itself is a known risk factor for diabetes.”
The February 2000 memo was prepared as background for a meeting of Lilly scientists to the possible changes for Zyprexa’s label.
According to the memo, Lilly scientists initially wanted to propose a relatively straightforward statement on the label that high blood sugar had been observed in patients taking Zyprexa in clinical trials. That change was never made.
Lilly’s analysis in early 2000 came at a time when some doctors and regulatory agencies were beginning to question whether Zyprexa could cause increases in blood sugar or diabetes. Although Lilly says that no link between Zyprexa and diabetes has ever been proven, the American Diabetes Association found in 2004 that Zyprexa was more likely to cause diabetes than other, similar drugs.
Zyprexa is by far Lilly’s best-selling product, with $4.2 billion in sales in 2005, which represented 30 percent of Lilly’s overall revenue. Zyprexa’s active ingredient is a potent chemical that binds to receptors in the brain to reduce the hallucinations and delusions associated with schizophrenia and acute bipolar disorder. About two million people worldwide took Zyprexa last year.
At the February 2000 meeting for which the memo was prepared, the agenda was to discuss Zyprexa’s tendency to cause high blood sugar, which is medically known as hyperglycemia.
According to the memo, Lilly had reviewed data from its clinical trials and found that “the incidence of treatment-emergent hyperglycemia in olanzapine group (3.6%) was higher than that in the placebo group (1.05%).” Olanzapine is the generic name for Zyprexa.
But when Lilly subsequently discussed the clinical trial results with doctors, it used a different comparison. Lilly told doctors that Zyprexa had caused 3.1 percent of patients — not 3.6 percent — to have high-blood sugar. And it said that 2.5 percent of patients on the placebo — not 1.05 percent — had high-blood sugar. As a result, the rates of high blood sugar in the two groups seemed almost identical in the revised data.


//www.nytimes.com/2006/12/17/business/17drug.html?ex=1324011600&en=37552a4a2b430b90&ei=5090&partner=rssuserland&emc=rss


Eli Lilly Said to Play Down Risk of Top Pill


By ALEX BERENSON
Published: December 17, 2006
The drug maker Eli Lilly has engaged in a decade-long effort to play down the health risks of Zyprexa, its best-selling medication for schizophrenia, according to hundreds of internal Lilly documents and e-mail messages among top company managers.


Darron Cummings/Associated Press
Zyprexa is Lilly’s top-selling drug, with sales of $4.2 billion last year.

Joshua Borough for The New York Times
James B. Gottstein, a lawyer who represents the mentally ill, said the documents about Zyprexa’s side effects raised public health issues.
The documents, given to The Times by a lawyer representing mentally ill patients, show that Lilly executives kept important information from doctors about Zyprexa’s links to obesity and its tendency to raise blood sugar — both known risk factors for diabetes.
Lilly’s own published data, which it told its sales representatives to play down in conversations with doctors, has shown that 30 percent of patients taking Zyprexa gain 22 pounds or more after a year on the drug, and some patients have reported gaining 100 pounds or more. But Lilly was concerned that Zyprexa’s sales would be hurt if the company was more forthright about the fact that the drug might cause unmanageable weight gain or diabetes, according to the documents, which cover the period 1995 to 2004.
Zyprexa has become by far Lilly’s best-selling product, with sales of $4.2 billion last year, when about two million people worldwide took the drug.
Critics, including the American Diabetes Association, have argued that Zyprexa, introduced in 1996, is more likely to cause diabetes than other widely used schizophrenia drugs. Lilly has consistently denied such a link, and did so again on Friday in a written response to questions about the documents. The company defended Zyprexa’s safety, and said the documents had been taken out of context.
But as early as 1999, the documents show that Lilly worried that side effects from Zyprexa, whose chemical name is olanzapine, would hurt sales.
“Olanzapine-associated weight gain and possible hyperglycemia is a major threat to the long-term success of this critically important molecule,” Dr. Alan Breier wrote in a November 1999 e-mail message to two-dozen Lilly employees that announced the formation of an “executive steering committee for olanzapine-associated weight changes and hyperglycemia.” Hyperglycemia is high blood sugar.
At the time Dr. Breier, who is now Lilly’s chief medical officer, was the chief scientist on the Zyprexa program.
In 2000, a group of diabetes doctors that Lilly had retained to consider potential links between Zyprexa and diabetes warned the company that “unless we come clean on this, it could get much more serious than we might anticipate,” according to an e-mail message from one Lilly manager to another.
And in that year and 2001, the documents show, Lilly’s own marketing research found that psychiatrists were consistently saying that many more of their patients developed high blood sugar or diabetes while taking Zyprexa than other antipsychotic drugs.
The documents were collected as part of lawsuits on behalf of mentally ill patients against the company. Last year, Lilly agreed to pay $750 million to settle suits by 8,000 people who claimed they developed diabetes or other medical problems after taking Zyprexa. Thousands more suits against the company are pending.
On Friday, in its written response, Lilly said that it believed that Zyprexa remained an important treatment for patients with schizophrenia and bipolar disorder. The company said it had given the Food and Drug Administration all its data from clinical trials and reports of adverse events, as it is legally required to do. Lilly also said it shared data from literature reviews and large studies of Zyprexa’s real-world use.
“In summary, there is no scientific evidence establishing that Zyprexa causes diabetes,” the company said.
Lilly also said the documents should not have been made public because they might “cause unwarranted fear among patients that will cause them to stop taking their medication.”
As did similar documents disclosed by the drug maker Merck last year in response to lawsuits over its painkiller Vioxx, the Lilly documents offer an inside look at how a company marketed a drug while seeking to play down its side effects. Lilly, based in Indianapolis, is the sixth-largest American drug maker, with $14 billion in revenue last year.
The documents — which include e-mail, marketing material, sales projections and scientific reports — are replete with references to Zyprexa’s importance to Lilly’s future and the need to keep concerns about diabetes and obesity from hurting sales. But that effort became increasingly difficult as doctors saw Zyprexa’s side effects, the documents show.
In 2002, for example, Lilly rejected plans to give psychiatrists guidance about how to treat diabetes, worrying that doing so would tarnish Zyprexa’s reputation. “Although M.D.’s like objective, educational materials, having our reps provide some with diabetes would further build its association to Zyprexa,” a Lilly manager wrote in a March 2002 e-mail message.
But Lilly did expand its marketing to primary care physicians, who its internal studies showed were less aware of Zyprexa’s side effects. Lilly sales material encouraged representatives to promote Zyprexa as a “safe, gentle psychotropic” suitable for people with mild mental illness.

Some top psychiatrists say that Zyprexa will continue to be widely used despite its side effects, because it works better than most other antipsychotic medicines in severely ill patients. But others say that Zyprexa appears no more effective overall than other medicines.
And some doctors who specialize in diabetes care dispute Lilly’s assertion that Zyprexa does not cause more cases of diabetes than other psychiatric drugs. “When somebody gains weight, they need more insulin, they become more insulin resistant,” Dr. Joel Zonszein, the director of the clinical diabetes center at Montefiore Medical Center in the Bronx, said when asked about the drug.
In 2003, after reviewing data provided by Lilly and other drug makers, the F.D.A. said that the current class of antipsychotic drugs may cause high blood sugar. It did not specifically single out Zyprexa, nor did it say that the drugs had been proven to cause diabetes.
The drugs are known as atypical antipsychotics and include Johnson & Johnson’s Risperdal and AstraZeneca’s Seroquel. When they were introduced in the mid-1990s, psychiatrists hoped they would relieve mental illness without the tremors and facial twitches associated with older drugs. But the new drugs have not proven significantly better and have their own side effects, said Dr. Jeffrey Lieberman, the lead investigator on a federally sponsored clinical trial that compared Zyprexa and other new drugs with one older one.
The Zyprexa documents were provided to the Times by James B. Gottstein, a lawyer who represents mentally ill patients and has sued the state of Alaska over its efforts to force patients to take psychiatric medicines against their will. Mr. Gottstein said the information in the documents raised public health issues.
“Patients should be told the truth about drugs like Zyprexa,” Mr. Gottstein said.
Lilly originally provided the documents, under seal, to plaintiffs lawyers who sued the company claiming their clients developed diabetes from taking Zyprexa. Mr. Gottstein, who is not subject to the confidentiality agreement that covers the product liability suits, subpoenaed the documents in early December from a person involved in the suits.
In its statement, Lilly called the release of the documents “illegal.” The company said it could not comment on specific documents because of the continuing product liability suits.
In some ways, the Zyprexa documents are reminiscent of those produced in litigation over Vioxx, which Merck stopped selling in 2004 after a clinical trial proved it caused heart problems. They treat very different conditions, but Zyprexa and Vioxx are not entirely dissimilar. Both were thought to be safer than older and cheaper drugs, becoming bestsellers as a result, but turned out to have serious side effects.
After being pressed by doctors and regulators, Merck eventually did test Vioxx’s cardiovascular risks and withdrew the drug after finding that Vioxx increased heart attacks and strokes.
Lilly has never conducted a clinical trial to determine exactly how much Zyprexa raises patients’ diabetes risks. But scientists say conducting such a study would be exceedingly difficult, because diabetes takes years to develop, and it can be hard to keep mentally ill patients enrolled in a clinical trial.
When it was introduced, Zyprexa was the third and most heralded of the atypical antipsychotics. With psychiatrists eager for new treatments for schizophrenia, bipolar disorder, and dementia, Zyprexa’s sales soared.
But as sales grew, reports rolled in to Lilly and drug regulators that the medicine caused massive weight gain in many patients and was associated with diabetes. For example, a California doctor reported that 8 of his 35 patients on Zyprexa had developed high blood sugar, including two who required hospitalization.
The documents show that Lilly encouraged its sales representatives to play down those effects when talking to doctors. In one 1998 presentation, for example, Lilly said its salespeople should be told, “Don’t introduce the issue!!!” Meanwhile, the company researched combinations of Zyprexa with several other drugs, hoping to alleviate the weight gain. But the combinations failed.
To reassure doctors, Lilly also publicly said that when it followed up with patients who had taken Zyprexa in a clinical trial for three years, it found that weight gain appeared to plateau after about nine months. But the company did not discuss a far less reassuring finding in early 1999, disclosed in the documents, that blood sugar levels in the patients increased steadily for three years.
In 2000 and 2001, more warning signs emerged, the documents show. In four surveys conducted by Lilly’s marketing department, the company found that 70 percent of psychiatrists polled had seen at least one of their patients develop high blood sugar or diabetes while taking Zyprexa, compared with about 20 percent for Risperdal or Seroquel. Lilly never disclosed those findings.
By mid-2003, Lilly began to change its stance somewhat, publicly acknowledging that Zyprexa can cause severe obesity. Marketing documents make clear that by then Lilly believed it had no choice. On June 23, 2003, an internal committee reported that Zyprexa sales were “below plan” and that doctors were “switching/avoiding Zyprexa.”
Since then, Lilly has acknowledged Zyprexa’s effect on weight but has argued that it does not necessarily correlate to diabetes. But Zyprexa’s share of antipsychotic drug prescriptions is falling, and some psychiatrists say they no longer believe the information Lilly offers.
“From my personal experience, at first my concerns about weight gain with this drug were very significantly downplayed by their field representatives,” said Dr. James Phelps, a psychiatrist in Corvallis, Or. ‘Their continued efforts to downplay that, I think in retrospect, was an embarrassment to the company.”
Dr. Phelps says that he tries to avoid Zyprexa because of its side effects but sometimes still prescribes it, especially when patients are acutely psychotic and considering suicide, because it works faster than other medicines.
“I wind up using it as an emergency medicine, where it’s superb,” he said. “But I’m trying to get my patients off of Zyprexa, not put them on.”


//www.nytimes.com/2006/12/18/business/18drug.html?pagewanted=1&ei=5090&en=780a71e0a5d91237&ex=1324098000&partner=rssuserland&emc=rss


Drug Files Show Maker Promoted Unapproved Use

By ALEX BERENSON
Published: December 18, 2006
Eli Lilly encouraged primary care physicians to use Zyprexa, a powerful drug for schizophrenia and bipolar disorder, in patients who did not have either condition, according to internal Lilly marketing materials.
The marketing documents, given to The New York Times by a lawyer representing mentally ill patients, detail a multiyear promotional campaign that Lilly began in Orlando, Fla., in late 2000. In the campaign, called Viva Zyprexa, Lilly told its sales representatives to suggest that doctors prescribe Zyprexa to older patients with symptoms of dementia.
A Lilly executive said that she could not comment on specific documents but that the company had never promoted Zyprexa for off-label uses and that it always showed the marketing materials used by its sales representatives to the Food and Drug Administration, as required by law.
“We have extensive training for sales reps to assure that they provide information to the doctors that’s within the scope of the prescribing information approved by the F.D.A.,” Anne Nobles, Lilly’s vice president for corporate affairs, said in an interview yesterday.
Zyprexa is not approved to treat dementia or dementia-related psychosis, and in fact carries a prominent warning from the F.D.A. that it increases the risk of death in older patients with dementia-related psychosis. Federal laws bar drug makers from promoting prescription drugs for conditions for which they have not been approved — a practice known as off-label prescription — although doctors can prescribe drugs to any patient they wish.
Yet in 1999 and 2000 Lilly considered ways to convince primary care doctors that they should use Zyprexa on their patients. In one document, an unnamed Lilly marketing executive wrote that these doctors “do treat dementia” but “do not treat bipolar; schizophrenia is handled by psychiatrists.”
As a result, “dementia should be first message,” of a campaign to primary doctors, according to the document, which appears to be part of a larger marketing presentation but is not marked more specifically.
Later, the same document says that some primary care doctors “might prescribe outside of label.”
Ms. Nobles said that the company had never promoted its drug for any conditions except schizophrenia and bipolar disorder. Older patients who seem to have dementia may actually have schizophrenia that has gone untreated, Ms. Nobles said.
Several psychiatrists outside the company said yesterday that they strongly disagreed with Lilly’s claim. Schizophrenia is a severe disease that is almost always diagnosed when patients are in their teens or 20s. Its symptoms could not be confused with mild dementia, these doctors said.
Zyprexa is by far Lilly’s best-selling product, with $4.2 billion in sales in 2005, 30 percent of its overall revenues. About two million people worldwide received it last year. Based in Indianapolis, Lilly is the sixth-largest American drug company.
The issue of off-label marketing is controversial in the drug industry. Nearly every company is under either civil or criminal investigation for alleged efforts to expand the use of its drugs beyond the specific illness or condition for which they are approved.
Lilly faces federal and state investigations over its marketing of Zyprexa. In its annual report for 2005, Lilly said that it faced an investigation by federal prosecutors in Pennsylvania and that the Florida attorney general’s office had subpoenaed the company “seeking production of documents relating to sales of Zyprexa and our marketing and promotional practices with respect to Zyprexa.”
Since Lilly introduced Zyprexa in 1996, about 20 million patients worldwide have received the drug, which helps control the hallucinations and delusions associated with schizophrenia and severe mania. But Zyprexa also causes weight gain in many patients, and the American Diabetes Association found in 2004 that Zyprexa was more likely to cause diabetes than other widely used drugs for schizophrenia.
Lilly says that no link between Zyprexa and diabetes has been proven.
As part of the “Viva Zyprexa” campaign, in packets for its sales representatives, Eli Lilly created the profiles of patients whom it said would be suitable candidates for Zyprexa. Representatives were told to discuss the patient profiles with doctors. One of the patients was a woman in her 20s who showed mild symptoms of schizophrenia, while another was a man in his 40s who appeared to have bipolar disorder.
The third patient was “Martha,” a widow with adult children “who lives independently and has been your patient for some time.” Martha was described as being agitated and having disturbed sleep, but without the symptoms of paranoia or mania that typically marked a person with schizophrenia or bipolar disorder.
Ms. Nobles said that Lilly had actually intended Martha’s profile to represent a patient with schizophrenia. But psychiatrists outside the company said this claim defied credibility, especially given Martha’s age. Instead, she appeared to have mild dementia, they said.
“It’d be very unusual for this to be a schizophrenic patient,” said Dr. John March, chief of child and adolescent psychiatry at Duke University medical center. “Schizophrenia is a disease of teenagers and young adults.” Dr. March serves on Lilly’s scientific advisory board.
Diagnostic criteria for schizophrenia include delusions, hallucinations, disorganized and incoherent speech, and grossly disorganized behavior. They also include so-called negative symptoms like social isolation and a flattening of the voice and facial expressions.
The documents also show that Lilly encouraged primary care doctors to treat the symptoms and behaviors of schizophrenia and bipolar disorder even if the doctors had not actually diagnosed those diseases in their patients. Lilly’s market research had found that many primary care doctors did not consider themselves qualified to treat people with schizophrenia or severe bipolar disorder.
The campaign was successful, the documents show. By March 2001, about three months after the start of Viva Zyprexa, the campaign had led to 49,000 new prescriptions, according to a presentation that Michael Bandick, the brand manager for Zyprexa, gave at a national meeting of Lilly sales representatives in Dallas. Mr. Bandick did not say how many of those new prescriptions were for older patients with dementia.
Over all, sales of Zyprexa doubled between 1999 and 2002, rising from $1.5 billion to $3 billion in the United States. In 2002, the company changed the name of the primary care campaign to “Zyprexa Limitless” and began to focus on people with mild bipolar disorder who had previously been diagnosed as depressed — even though Zyprexa has been approved only for the treatment of mania in bipolar disorder, not depression.
In a 2002 guide for representatives, Lilly presented the profile of “Donna,” a single mother in her mid-30s whose “chief complaint is, ‘I feel so anxious and irritable lately.’ ” Several doctors’ appointments earlier, she was “talkative, elated, and reported little need for sleep.”
Lilly’s efforts to promote Zyprexa to primary care doctors disturbed some physicians, the documents show. In August 2001, a doctor in Virginia sent an e-mail message to Lilly and the F.D.A., complaining about a presentation from a Lilly sales representative who had discussed the hypothetical Martha with him.
The representative “presented an elderly female patient who was presented to her physician by her family complaining of insomnia, agitation, slight confusion, and had no physical finding to explain her state,” the doctor wrote. The representative then suggested that the doctor prescribe Zyprexa.
“I inquired what Zyprexa was indicated for she then indicated that many physicians might prescribe an antipsychotic for this patient. I then asked for her package insert and read to her that her product was indicated for schizophrenia and bipolar mania — neither of which the presented patient had been diagnosed with,” the doctor wrote.
He added that he had never contacted the F.D.A. before but was “genuinely concerned about the promotion of this powerful drug to my peer community of primary care physicians outside of its approved and intended purpose.”
Tara Ryker, a spokeswoman for Lilly, said the company no longer uses “Martha” or “Donna” in its marketing. “We are constantly developing new promotional materials and new profiles,” she said.
The Zyprexa documents were provided to The Times by James B. Gottstein, a lawyer who represents mentally ill patients and has sued the state of Alaska over its efforts to force patients to take psychiatric medicines against their will.
Mr. Gottstein said yesterday that the information in the documents should be available to patients and doctors, as well as judges who oversee the hearings that are required before people can be forced to take psychiatric drugs.
“The courts should have this information before they order this stuff injected into people’s unwilling bodies,” Mr. Gottstein said.
Lilly originally provided the documents, under seal, to plaintiffs lawyers who sued the company claiming their clients developed diabetes from taking Zyprexa. Last year, Lilly agreed to pay $700 million to settle about 8,000 of the claims, but thousands more are pending. Mr. Gottstein, who is not subject to the confidentiality agreement that covers the product liability suits, subpoenaed the documents in early December from a person involved in the suits.
The “Viva Zyprexa” documents also provide color about Lilly’s efforts to motivate its sales force as they marketed Zyprexa — whose generic name is olanzapine — to primary care doctors.
At the 2001 meeting in Dallas with Zyprexa sales representatives, Mr. Bandick praised 16 representatives by name for the number of prescriptions they had convinced doctors to write, according to a script prepared in advance of the meeting. More than 100 other representatives had convinced doctors to write at least 16 extra prescriptions and thus “maxed out on a pretty sweet incentive,” he said.
“Olanzapine is the molecule that keeps on giving,” Mr. Bandick said.