title: The paroxetine 352 bipolar trial: A study in medical ghostwriting.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Depression Research Unit, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. enopath@aol.com
authors.forename: Jay D
authors.initials: JD
authors.lastname: Amsterdam
authors.forename: Leemon B
authors.initials: LB
authors.lastname: McHenry
mesh_terms: D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000627:therapeutic use*; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D016265:Conflict of Interest; D004311:Double-Blind Method; D006801:Humans; D007099:Imipramine / Q000009:adverse effects / Q000627:therapeutic use*; D017374:Paroxetine / Q000009:adverse effects / Q000627:therapeutic use*; D015871:Scientific Misconduct; D016896:Treatment Outcome
chemical_list: D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D017374:Paroxetine; D007099:Imipramine