International Journal of Risk & Safety in Medicine 24 (2012) 221–231 DOI 10.3233/JRS-2012-0571 IOS Press 221 The paroxetine 352 bipolar trial: A study in medical ghostwriting Jay D. Amsterdam a,* and Leemon B. McHenry b a Depression Research Unit, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA b Department of Philosophy, California State University, Northridge, CA, USA Abstract. Background: The problem of ghostwriting in corporate-sponsored clinical trials is of concern to medicine, bioethics, and government agencies. We present a study of the ghostwritten archival report of an industry-sponsored trial comparing antidepressant treatments for bipolar depression: GlaxoSmithKline (GSK) paroxetine study 352. This analysis is based upon publicly available evidence presented in a complaint of research misconduct filed with the Office of Research Integrity of the Department of Health and Human Services. Objectives: We performed a deconstruction of the published study to show how primary and secondary outcome analyses were conflated, turning a ‘negative’ clinical trial into a ‘positive’ study – with conclusions and recommendations that could adversely affect patient health. Methods: The paroxetine 352 study was a randomized, double-blind, placebo-controlled, 19-site trial comparing paroxetine and imipramine in 117 patients with bipolar type I major depressive episode which was unresponsive to prior lithium carbonate therapy. Results: Analysis of the primary outcome measures found no statistically significant difference between paroxetine or imipramine versus placebo. However, the published article concluded that both drugs were efficacious versus placebo for a post hoc subgroup of patients. Conclusions: Few industry-sponsored studies gain public scrutiny. It is important to make these articles transparent to the scientific and medical community. Keywords: Ghostwriting, key opinion leaders, depression, bipolar, SSRI, paroxetine, litigation, industry sponsorship 1. Introduction The problem of truth and transparency in published scientific reports of corporate-sponsored clinical trials has been an on-going concern in the medical and bioethics literature. The difference between what a trial should report and what is actually reported in the medical journals in the past 30 years is so alarming that some editors have declared a crisis of credibility [1]. Details of selective data reporting, misrepresentation of results, and ghostwriting of manuscripts have been revealed from the fragmentary release of documents publicly disclosed in litigation in the United States [2]. Critical evaluation of these practices, however, is sporadic at best because of inherent non-disclosure or inaccessibility of * Address for correspondence: Jay D. Amsterdam, MD, Depression Research Unit, University Science Center – 3rd Floor, 3535 Market Street, Philadelphia, PA 19104, USA. Tel.: +1 215 662 3462; Fax: +1 215 662 6443; E-mails: enopath@aol.com, jamsterd@mail.med.upenn.edu. 0924-6479/12/$27.50 © 2012 – IOS Press and the authors. All rights reserved