Implementation of a publication strategy in the context of reporting biases. A case study based on new documents from Neurontin litigation.
BACKGROUND
Previous studies have documented strategies to promote off-label use of drugs using journal publications and other means. Few studies have presented internal company communications that discussed financial reasons for manipulating the scholarly record related to off-label indications. The objective of this study was to build on previous studies to illustrate implementation of a publication strategy by the drug manufacturer for four off-label uses of gabapentin (Neurontin, Pfizer, Inc.): migraine prophylaxis, treatment of bipolar disorders, neuropathic pain, and nociceptive pain.


METHODS
We included in this study internal company documents, email correspondence, memoranda, study protocols and reports that were made publicly available in 2008 as part of litigation brought by consumers and health insurers against Pfizer for fraudulent sales practices in its marketing of gabapentin (see http://pacer.mad.uscourts.gov/dc/cgi-bin/recentops.pl?filename=saris/pdf/ucl%20opinion.pdf for the Court's findings).We reviewed documents pertaining to 20 clinical trials, 12 of which were published. We categorized our observations related to reporting biases and linked them with topics covered in internal documents, that is, deciding what should and should not be published and how to spin the study findings (re-framing study results to explain away unfavorable findings or to emphasize favorable findings); and where and when findings should be published and by whom.


RESULTS
We present extracts from internal company marketing assessments recommending that Pfizer and Parke-Davis (Pfizer acquired Parke-Davis in 2000) adopt a publication strategy to conduct trials and disseminate trial findings for unapproved uses rather than an indication strategy to obtain regulatory approval. We show internal company email correspondence and documents revealing how publication content was influenced and spin was applied; how the company selected where trial findings would be presented or published; how publication of study results was delayed; and the role of ghost authorship.


CONCLUSIONS
Taken together, the extracts we present from internal company documents illustrate implementation of a strategy at odds with unbiased study conduct and dissemination. Our findings suggest that Pfizer and Parke-Davis's publication strategy had the potential to distort the scientific literature, and thus misinform healthcare decision-makers.
Department of Epidemiology, Center for Clinical Trials, Johns Hopkins Bloomberg School of Public Health, 615 N, Wolfe Street, Mailroom W5010, Baltimore, MD 21205, USA.
S Swaroop
SS
Vedula
Palko S
PS
Goldman
Ilyas J
IJ
Rona
Thomas M
TM
Greene
Kay
K
Dickersin
D022126:Access to Information; D000588:Amines / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D000700:Analgesics / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D018692:Antimanic Agents / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D001319:Authorship; D001714:Bipolar Disorder / Q000188:drug therapy; D002986:Clinical Trials as Topic; D016265:Conflict of Interest; D015709:Correspondence as Topic; D003509:Cyclohexanecarboxylic Acids / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D004282:Documentation; D016527:Drug Costs; D004345:Drug Industry / Q000191:economics / Q000331:legislation & jurisprudence; D034742:Electronic Mail; D019317:Evidence-Based Medicine; D005607:Fraud; D000077206:Gabapentin; D006801:Humans; D008389:Marketing of Health Services / Q000191:economics / Q000331:legislation & jurisprudence; D008881:Migraine Disorders / Q000517:prevention & control; D009437:Neuralgia / Q000188:drug therapy; D059226:Nociceptive Pain / Q000188:drug therapy; D056687:Off-Label Use / Q000191:economics / Q000331:legislation & jurisprudence; D010506:Periodicals as Topic / Q000191:economics / Q000331:legislation & jurisprudence; D017594:Publication Bias; D005680:gamma-Aminobutyric Acid / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*
D000588:Amines; D000700:Analgesics; D018692:Antimanic Agents; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin