This paper is a deconstruction of a ghostwritten report of a randomized, double-blind, placebo-controlled efficacy and safety trial of citalopram in depressed children and adolescents conducted in the United States. Court documents revealed that protocol-specified outcome measures showed no statistically significant difference between citalopram and placebo. However, the published article concluded that citalopram was safe and significantly more efficacious than placebo for children and adolescents, with possible adverse effects on patient safety.

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.

Medical ghostwriting is the practice in which pharmaceutical companies engage an outside writer to draft a manuscript submitted for publication in the names of “honorary authors,” typically academic key opinion leaders. Using newly-posted documents from paroxetine litigation, we show how the use of ghostwriters and key opinion leaders contributed to the publication of a medical journal article containing manipulated outcome data to favor the proprietary medication. The article was ghostwritten and managed by SmithKline Beecham, now GlaxoSmithKline (GSK) and Scientific Therapeutics (...) Information, Inc. without acknowledging their contribution in the published article. The named authors with financial ties to GSK, had little or no direct involvement in the paroxetine 352 bipolar trial results and most had not reviewed any of the manuscript drafts. The manuscript was originally rejected by peer review; however, its ultimate acceptance to the American Journal of Psychiatry was facilitated by the journal editor who also had financial ties to GSK. Thus, GSK was able to take an under-powered and non-informative trial with negative results and present it as a positive marketing vehicle for off-label promotion of paroxetine for bipolar depression. In addition to the commercial spin of paroxetine efficacy, important protocol-designated safety data were unreported that may have shown paroxetine to produce potentially harmful adverse events. (shrink)

The goal of this paper is to expose the research misconduct of pharmaceutical industry-sponsored clinical trials via three short case studies of corrupted psychiatric trials that were conducted in the United States. We discuss the common elements that enable the misrepresentation of clinical trial results including ghostwriting for medical journals, the role of key opinion leaders as co-conspirators with the pharmaceutical industry and the complicity of top medical journals in failing to uphold standards of science and peer review. We conclude (...) that the corruption of industry-sponsored clinical trials is one of the major obstacles facing evidence-based medicine. (shrink)