Behold – not all scientific research, including clinical trials intended for drug registrations, would be objective and unbiased. Two new studies comparing published research articles with insider documents obtained during the rofecoxib (Vioxx) lawsuits offer a glimpse into the manipulation of the drug industry.

The startling revelations were published in the April 16, 2008 issue of the JAMA. In one analysis, researchers used court documents released during the litigation process to show that many manuscripts were written by the sponsor or by third-party medical-publishing ghostwriters, then attributed to a reputable academic who, in some cases, was paid to have his or her name used.

The second paper also used documents obtained during litigation to demonstrate that mortality rates of patients taking Vioxx, reported in published manuscripts, were lower than those described in internal company documents.

An accompanying editorial by journal editors Drs Catherine D DeAngelis and Phil B Fontanarosa explores what steps can be taken to reduce the influence of for-profit companies on clinical research, making it clear that the issues highlighted are likely not infrequent. In a statement, MSD (the maker of Vioxx) has said that the company believes many of the comments in the JAMA papers are "false, misleading, or lack context."

The hidden hands
In the first study, Dr Joseph Ross (Mount Sinai School of Medicine, New York, NY) and colleagues identified approximately 250 documents, ranging from internal and external letters and emails to reports, presentations, and receipts that were relevant to their study, then linked these to subsequently published clinical-trial results or scientific review papers. They found evidence of MSD employees preparing manuscripts, sometimes in collaboration with medical publishing companies, and then recruiting academic physicians to be the first authors. For review papers, Ross et al found documents describing MSD’s marketing teams hatching plans for review papers, contracting ghostwriters to conduct and write the articles, then recruiting academics to be authors. Of 96 published articles, 92% of clinical-trial publications (22 out of a total of 24 papers) disclosed financial support from MSD, but only 50% of review articles disclosed Merck's backing or included any mention of the author's financial compensation.

The motivation
"There is so much money in cardiovascular medicine, it's such an important field, and there are so many blockbuster products". This statement by Dr Harlan H Krumholz of Yale University sums up a lot of imperatives that drive the drug industry. It's just endemic in the entire field that people supplement their incomes and CVs to be associated with scientific activities which have lucrative commercial potentials – ie. to put onto market a new blockbuster drug. “

“Unbiasedness” challenged
It’s obvious that such publication in JAMA attracted uneasiness from MSD, who issued a statement to explain that the company was given no chance to respond to the papers before their publication in JAMA and that an "unbiased review" of the MSD documents showed "significant errors in the conclusions put forward by the authors of the JAMA articles." The statement also emphasized that the articles were written by people who were also paid consultants for plaintiff lawyers during the Vioxx lawsuits, a point also made by the editorialists.

Ensuring future credibility of publication…..
In their editorial, DeAngelis and Fontanarosa pointed out that journal editors shoulder some of the blame for "enabling" companies to influence published information without mandating more thorough disclosure procedures, but the problem infects all parties. They propose 11 suggestions for "drastic action" to improve transparency in medical research:

1. 1. Registration of all clinical trials, with names of principal investigator(s) included. 
   2. Disclosure by all authors of the extent of their involvement in manuscript preparation, including the names of individuals who helped but are not listed as authors.
   3. Disclosure by journals of funding sources for articles and relationships between authors and for-profit companies.
   4. Consideration by journals of how funding sources influenced manuscripts during initial review for publication. 
   5. Sole or primary responsibility for research belonging to academic investigators, not companies. 
   6. Independent statistical review of clinical-trial data by someone not involved with a for-profit company. 
   7. Mandatory reporting of authors to appropriate authority (dean or department chair) if they do not report financial relationships or allow their names to be added to manuscripts. 
   8. Mandatory reporting to appropriate authority of peer reviewers who provide confidential information to third parties; banning of these reviewers from future reviewing or publishing in the journal. 
   9. Removal of a journal editor if he/she is found to have permitted for-profit companies to manipulate journal. 
   10. Prohibition of companies from having input into content of educational materials created by professional societies or medical-education programs. 
   11. Freedom from influence of companies over individuals relating to speakers' bureaus, acceptance of gifts.

Adapted from:
• Ross JS, Hill KP, Egilman DS, Krumholz HM. Guest authorship and ghostwriting in publications related to rofecoxib. A case study of industry documents from rofecoxib litigation. JAMA 2008; 299:1800-1812.
• Psaty BM, Kronmal RA. Reporting mortality findings in trials of rofecoxib for Alzheimer disease or cognitive impairment. A case study based on documents from rofecoxib litigation. JAMA 2008; 299:1813-1817.
• DeAngelis CD, Fontanarosa PB. Impugning the integrity of medical science the adverse effects of industry influence. JAMA 2008; 299:1833-1835.

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