Strategies and Practices in Off-Label Marketing of Pharmaceuticals: A Retrospective Analysis of Whistleblower Complaints
Background:
Despite regulatory restrictions, off-label marketing of pharmaceutical
products has been common in the US. However, the scope of off-label
marketing remains poorly characterized. We developed a typology for the
strategies and practices that constitute off-label marketing.
Methods and Findings:
We obtained unsealed whistleblower complaints against pharmaceutical
companies filed in US federal fraud cases that contained allegations of
off-label marketing (January 1996–October 2010) and conducted
structured reviews of them. We coded and analyzed the strategic goals of
each off-label marketing scheme and the practices used to achieve those
goals, as reported by the whistleblowers. We identified 41 complaints
arising from 18 unique cases for our analytic sample (leading to
US$7.9 billion in recoveries). The off-label marketing schemes
described in the complaints had three non–mutually exclusive goals:
expansions to unapproved diseases (35/41, 85%), unapproved disease
subtypes (22/41, 54%), and unapproved drug doses (14/41, 34%).
Manufacturers were alleged to have pursued these goals using four
non–mutually exclusive types of marketing practices:
prescriber-related (41/41, 100%), business-related (37/41,
90%), payer-related (23/41, 56%), and consumer-related (18/41,
44%). Prescriber-related practices, the centerpiece of company
strategies, included self-serving presentations of the literature (31/41,
76%), free samples (8/41, 20%), direct financial incentives to
physicians (35/41, 85%), and teaching (22/41, 54%) and
research activities (8/41, 20%).
Conclusions:
Off-label marketing practices appear to extend to many areas of the health
care system. Unfortunately, the most common alleged off-label marketing
practices also appear to be the most difficult to control through external
regulatory approaches.
Please see later in the article for the Editors' Summary
Vyšlo v časopise:
Strategies and Practices in Off-Label Marketing of Pharmaceuticals: A Retrospective Analysis of Whistleblower Complaints. PLoS Med 8(4): e32767. doi:10.1371/journal.pmed.1000431
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pmed.1000431
Souhrn
Background:
Despite regulatory restrictions, off-label marketing of pharmaceutical
products has been common in the US. However, the scope of off-label
marketing remains poorly characterized. We developed a typology for the
strategies and practices that constitute off-label marketing.
Methods and Findings:
We obtained unsealed whistleblower complaints against pharmaceutical
companies filed in US federal fraud cases that contained allegations of
off-label marketing (January 1996–October 2010) and conducted
structured reviews of them. We coded and analyzed the strategic goals of
each off-label marketing scheme and the practices used to achieve those
goals, as reported by the whistleblowers. We identified 41 complaints
arising from 18 unique cases for our analytic sample (leading to
US$7.9 billion in recoveries). The off-label marketing schemes
described in the complaints had three non–mutually exclusive goals:
expansions to unapproved diseases (35/41, 85%), unapproved disease
subtypes (22/41, 54%), and unapproved drug doses (14/41, 34%).
Manufacturers were alleged to have pursued these goals using four
non–mutually exclusive types of marketing practices:
prescriber-related (41/41, 100%), business-related (37/41,
90%), payer-related (23/41, 56%), and consumer-related (18/41,
44%). Prescriber-related practices, the centerpiece of company
strategies, included self-serving presentations of the literature (31/41,
76%), free samples (8/41, 20%), direct financial incentives to
physicians (35/41, 85%), and teaching (22/41, 54%) and
research activities (8/41, 20%).
Conclusions:
Off-label marketing practices appear to extend to many areas of the health
care system. Unfortunately, the most common alleged off-label marketing
practices also appear to be the most difficult to control through external
regulatory approaches.
Please see later in the article for the Editors' Summary
Zdroje
1. Kefauver-Harris Drug Amendments
1962
Public Law 87-781 (codified as amended at 21 U.S.C. § 352
(n))
2. Fugh-Berman
A
Melnick
D
2008
Off-label promotion, on-target sales.
PLoS Med
5
e210
doi:10.1371/journal.pmed.0050210
3. Psaty
BM
Ray
W
2008
FDA guidance on off-label promotion and the state of the
literature from sponsors.
J Amer Med Assn
299
1949
1951
4. Henney
JE
2006
Safeguarding patient welfare: who's in
charge?
Ann Intern Med
145
305
307
5. Kesselheim
AS
Avorn
J
2008
Pharmaceutical promotion to physicians and First Amendment
rights.
New Engl J Med
358
1727
1732
6. Kesselheim
AS
Studdert
DM
2008
Whistleblower-initiated enforcement actions against health care
fraud and abuse in the United States, 1996 to 2005.
Ann Int Med
149
342
349
7. Almashat
S
Preston
C
Waterman
T
Wolfe
S
2010
December
16
Rapidly increasing criminal and civil monetary penalties against
the pharmaceutical industry: 1991 to 2010.
Available: http://www.citizen.org/hrg1924. Accessed 10 February
2011
8. Harris
G
2009
September
2
Pfizer pays $2.3 billion to settle marketing
case.
NY Times B4
9. Department of Justice
2010
April
29
Two Johnson & Johnson subsidiaries to pay over $81
million to resolve allegations of off-label promotion of
Topamax.
Available: http://www.justice.gov/opa/pr/2010/April/10-civ-500.html.
Accessed 10 February 2011
10. Department of Justice
2010
April
27
Pharmaceutical giant AstraZeneca to pay $520 million for
off-label drug marketing.
Available: http://www.justice.gov/opa/pr/2010/April/10-civ-487.html.
Accessed 10 February 2011
11. Department of Justice
2010
May
4
Novartis vaccines & diagnostics to pay more than $72
million to resolve False Claims Act allegations concerning
TOBI.
Available: http://www.justice.gov/opa/pr/2010/May/10-civ-522.html.
Accessed 10 February 2011
12. Department of Justice
2010
September
15
Drug maker Forest pleads guilty; to pay more than $313
million to resolve criminal charges and False Claims Act
allegations.
Available: http://www.justice.gov/opa/pr/2010/September/10-civ-1028.html.
Accessed 10 February 2011
13. Department of Justice
2010
September
30
Novartis Pharmaceuticals Corp. to pay more than $420
million to resolve off-label promotion and kickback allegations. 30 Sept
2010.
Available: http://www.justice.gov/opa/pr/2010/September/10-civ-1102.html.
Accessed 10 February 2011
14. Department of Justice
2010
September
1
Allergan agrees to plead guilty and pay $600 million to
resolve allegations of off-label promotion of Botox®.
Available: http://www.justice.gov/opa/pr/2010/September/10-civ-988.html.
Accessed 10 February 2011
15. Sandburg
B
2009
Health care fraud investigations bedevil Pharma industry: if
you're not under investigation, it's only because you've
recently settled.
Pink Sheet
71
21
24
16. Hill
KP
Ross
JS
Egilman
DS
Krumholz
HM
2008
The ADVANTAGE seeding trial: a review of internal
documents.
Ann Intern Med
149
251
258
17. Ross
JS
Hill
KP
Egilman
DS
Krumholz
HM
2008
Guest authorship and ghostwriting in publications related to
rofecoxib: a case study of industry documents from rofecoxib
litigation.
J Amer Med Assn
299
1800
1812
18. Spielmans
GI
2009
The promotion of olanzapine in primary care: an examination of
internal industry documents.
Soc Sci Med
69
14
20
19. Steinman
MA
Harper
GM
Chren
MM
Landefeld
CS
Bero
LA
2007
Characteristics and impact of drug detailing for
gabapentin.
PLoS Med
4
e134
doi:10.1371/journal.pmed.0040134
20. Steinman
MA
Bero
LA
Chren
MM
Landefeld
CS
2006
Narrative review: the promotion of gabapentin: an analysis of
internal industry documents.
Ann Intern Med
145
284
293
21. Fugh-Berman
A
Ahari
S
2007
Following the script: how drug reps make friends and influence
doctors.
PLoS Med
4
e150
doi:10.1371/journal.pmed.0040150
22. Waxman
HA
2005
May
5
Memorandum re: marketing of Vioxx to physicians.
Available: http://oversight.house.gov/documents/20050505114932-41272.pdf.
Accessed 10 February 2011
23. Kesselheim
AS
Studdert
DM
Mello
MM
2010
Experiences of whistle-blowers in major fraud litigation against
pharmaceutical companies.
New Engl J Med
362
1832
1839
24. Mello
MM
Studdert
DM
Brennan
TA
2009
Shifting terrain in the regulation of off-label promotion of
pharmaceuticals.
New Engl J Med
360
1557
1566
25. United States Department of Justice
2011
Office of Public Affairs Press Releases.
Available: http://www.usdoj.gov/03press/03_1_1.html. Accessed 10
February 2011
26. United States Judiciary
2011
Public Access to Court Electronic Records.
Available: http://pacer.psc.uscourts.gov/. Accessed 10 February
2011
27. Glaser
BG
Strauss
AL
1967
The discovery of grounded theory: strategies for qualitative
research
New York
Aldine De Gruyter Press
274
28. Constas
MA
1992
Qualitative data analysis as a public event: the documentation of
category development procedures.
American Educational Research Journal
29
253
266
29. US ex rel. Franklin v. Parke-Davis, Division of Warner-Lambert
Company
1996 August 13
Civil Action 1:96-CV-11651-PBS.
Available: http://www.drugepi.org/downloads/downloads/WarnerLambert_Complaint1.pdf.
Accessed 10 February 2011
30. US ex rel. Collins, et al. v. Pfizer, Inc
2007 August 13
Civil Action 1:04-CV-11780-DPW.
Available: http://www.drugepi.org/downloads/downloads/Pfizer_Complaint8.pdf.
Accessed 10 February 2011
31. US, et al. ex rel. Lauterbach v. Orphan Medical Inc., Jazz
Pharmaceuticals Inc., and Dr. Peter Gleason
2006 February 17
Civil Action 05-CV-0387-SJF-KAM.
Available: http://www.drugepi.org/downloads/downloads/OrphanMedical_Complaint1.pdf.
Accessed 10 February 2011
32. US, et al. ex rel. Boise v. Cephalon, Inc
2008 January 3
Civil Action 2:04-CV-04401-TON.
Available: http://www.drugepi.org/downloads/downloads/Cephalon_Complaint4.pdf.
Accessed 10 February 2011
33. US ex rel. Kopchinski v. Pfizer, Inc. and Pharmacia Corp
2005 October 24
Civil Action 1:05-CV-12115-DPW.
Available: http://www.drugepi.org/downloads/downloads/Pfizer_Complaint7.pdf.
Accessed 10 February 2011
34. US, et al. ex rel. Stromv. Scios, Inc. and Johnson & Johnson,
Inc
2005 July 22
Civil Action 3:05-CV-03004-CRB.
Available: http://www.drugepi.org/downloads/downloads/Scios_Complaint2.pdf.
Accessed 10 February 2011
35. US, et al. ex rel. Mulqueen, et al. v. Medicis Pharmaceutical
Corp
2007 April 5
Civil Action 2:04-CV-02389-KHV-GLR.
Available: http://www.drugepi.org/downloads/downloads/Medicis_Complaint1.pdf.
Accessed 10 February 2011
36. US, et al. ex rel. Gobble v. Forest Laboratories Inc., Forest
Pharmaceuticals, Inc
2010 January 8
Civil Action 03-10395-NMG.
Available: http://www.drugepi.org/downloads/downloads/Forest_Complaint1.pdf.
Accessed 10 February 2011
37. US, et al. ex rel. Copeland v. Novartis Pharmaceuticals Corp
2010 August 26
Civil Action 2:06-CV-01630-LDD.
Available: http://www.drugepi.org/downloads/downloads/NovartisCase2_Complaint1.pdf.
Accessed 10 February 2011
38. US, et al. ex rel. Sandler and Paris v. Wyeth Pharmaceuticals, Inc. and
Pfizer Inc
2010 May 24
Civil Action 2:05-CV-06609-JP.
Available: http://www.drugepi.org/downloads/downloads/Wyeth_Complaint1.pdf.
Accessed 10 February 2011
39. US ex rel. Marchese v. Cell Therapeutics, Inc., et al
2007 August 24
Civil Action 2:06-CV-00168-MJP.
Available: http://www.drugepi.org/downloads/downloads/CellTherapeutics_Complaint1.pdf.
Accessed 10 February 2011
40. US, et al. ex rel. Kruszewski v. Pfizer, Inc
2009 August 21
Civil Action 2:07-CV-04106-JCJ.
Available: http://www.drugepi.org/downloads/downloads/Pfizer_Complaint5.pdf.
Accessed 10 February 2011
41. US, et al. ex rel. Wetta v. AstraZeneca Corporation
2008 August 1
Civil Action 2:04-CV-03479-BMS.
Available: http://www.drugepi.org/downloads/downloads/AstraZeneca_Complaint1.pdf.
Accessed 10 February 2011
42. US ex rel. Gallagher v. Intermune, Inc
2004 July 9
Civil Action 04:CV-4323.
Available: http://www.drugepi.org/downloads/downloads/Intermune_Complaint1.pdf.
Accessed 10 February 2011
43. US ex rel. Westlock v. Pfizer, Inc., et al
2008 August 1
Civil Action 1:08-CV-11318-DPW.
Available: http://www.drugepi.org/downloads/downloads/Pfizer_Complaint2.pdf.
Accessed 10 February 2011
44. US ex rel. Liter v. Pfizer, Inc
2007 November 21
Civil Action 2:06-CV-00176-WOB.
Available: http://www.drugepi.org/downloads/downloads/Pfizer_Complaint1.pdf.
Accessed 10 February 2011
45. US ex rel. Farber and Schildhauer v. Pfizer, Inc
2007 June 12
Civil Action 1:07-CV-10304-DPW.
Available: http://www.drugepi.org/downloads/downloads/Pfizer_Complaint6.pdf.
Accessed 10 February 2011
46. US ex rel. Smith v. Scios, Inc., et al
2005 October 7
Civil Action 3:05-CV-04055-CRB.
http://www.drugepi.org/downloads/downloads/Scios_Complaint1.pdf.
Accessed 10 February 2011
47. US ex rel. Lang and Rushin v. Allergan, Inc
2007 June 5
Civil Action 1:07-CV-01288-WSD.
Available: http://www.drugepi.org/downloads/downloads/Allergan_Complaint2.pdf.
Accessed 10 February 2011
48. US, et al. ex rel. Garcia and Driscoll v. Serono, Inc
2003 October 6
Civil Action 03-CV-11892-GAO.
Available: http://www.drugepi.org/downloads/downloads/Serono_Complaint1.pdf.
Accessed 10 February 2011
49. Drazen
JM
de Leeuw
PW
Laine
C
Mulrow
C
DeAngelis
CD
2010
Toward more uniform conflict disclosures—the updated ICMJE
conflict of interest reporting form.
New Engl J Med
363
188
189
50. Physician Payments Sunshine Act
2009
H.R. 3590 § 6002
51. PhRMA
2008
Code on interactions with health care
professionals.
Available: http://www.phrma.org/files/attachments/PhRMA%20Marketing%20Code%202008.pdf.
Accessed 10 February 2011
52. Pollack
A
2006 September 12
Stanford to ban drug makers' gifts to doctors, even
pens.
NY Times C2
53. Edney
A
2010 October 15
Drugmaker CEOs may be targets for U.S. FDA in off-label cases,
lawyer says.
Bloomberg News. Available: http://www.bloomberg.com/news/2010-10-14/drugmaker-executives-may-become-targets-of-fda-for-off-label-promotions.html.
Accessed 10 February 2011
54. Wilson
D
2010 November 9
Ex-Glaxo executive is charged in drug fraud.
NY Times B2
55. Kindler
J
2010 March 17
Business must change to earn back the public's
trust.
Reuters. Available: http://blogs.reuters.com/great-debate/2010/03/17/business-must-change-to-earn-back-the-publics-trust/.
Accessed 10 February 2011
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