Product liability litigation involving rofecoxib (Vioxx) has led to the disclosure of materials that has provided direct evidence of something that has long been suspected but well-hidden by industry; the manipulation of pharmaceutical studies by for-profit manufacturers of pharmaceuticals and medical devices of study results, using authors, editors, and reviewers to misrepresent research data and manipulate clinical research articles and clinical reviews.
Reports published in the Journal of the American Medical Association (JAMA) based upon a review of materials disclosed by Merck & Co. in the course of the Vioxx litigation claim Merck & Co. frequently paid academic scientists to take credit for research articles prepared by company-hired medical writers, a practice called “ghostwriting”. The reports also contend Merck tried to minimize deaths in two studies that showed that the now withdrawn Vioxx did not work at treating or preventing Alzheimer’s disease.
That this information of the manipulation of pharmaceutical studies came out only because of litigation should, but probably won’t, give pause to those who believe that the U.S. Supreme Court would be correct to determine in a case pending before it that the doctrine of federal pre-emption precludes product liability lawsuits against manufacturers of drugs that have been approved by the Food and Drug Agency (FDA).
The FDA has itself acknowledged that it lacks sufficient resources to independently evaluate the efficacy and safety of the pharmaceuticals that it reviews. Thus with the under-financed FDA having unchallengeable authority to approve a drug, what recourse will a consumer have if he or she is injured by a drug? In a word, “None.” And some argue that this would be a good thing!
The reports in JAMA conclude that this case-study review of industry documents demonstrates that clinical trial manuscripts related to rofecoxib were authored by sponsor employees but often attributed first authorship to academically affiliated investigators who did not always disclose industry financial support, another example of manipulation of pharmaceutical studies.
Review manuscripts were often prepared by unacknowledged authors and subsequently attributed authorship to academically affiliated investigators who often did not disclose industry financial support.
Among 96 relevant published articles, the reports found that 92% (22 of 24) of clinical trial articles published a disclosure of Mercks financial support, but only 50% (36 of 72) of review articles published either a disclosure of Merck sponsorship or a disclosure of whether the author had received any financial compensation from the company.
JAMA’s editorial board expressed their outrage at the manipulation of pharmaceutical studies in an editorial. According to Dr. Catherine DeAngelis, JAMA’s editor-in-chief, the practices outlined in JAMA can lead editors to publish biased research that can result in doctors giving patients improper and even harmful treatment.
Other comments in the editorial include: “The profession of medicine, in every aspect clinical, education, and research has been inundated with profound influence from the pharmaceutical and medical device industries. This has occurred because physicians have allowed it to happen, and it is time to stop. … However, it is clear that at least some of the authors played little direct roles in the study or review, yet still allowed themselves to be named as authors. Individuals, particularly physicians, who allow themselves to be used in this way, especially for financial gain, manifest a behavior that is unprofessional and demeaning to the medical profession and to scientific research.”
JAMA’s editors urged the adoption “as a beginning” of an eleven-point list of strict reforms, including a ghostwriting crackdown and requiring all authors to spell out their specific roles:
1. All clinical trials must be prospectively listed in registries accepted by the International Committee of Medical Journal Editors (ICMJE) prior to patient enrollment, and the name(s) of the principal investigator(s) should be included as a required data element in the trial registration record.
2. All individuals named as authors on articles must fulfill authorship criteria. Journals should require each author to report his or her specific contributions to the article, and should consider publishing these contributions. All individuals who were involved with the manuscript or study but who do not qualify for authorship (such as those who provided writing assistance) must be named in the acknowledgment section of the article, with reporting of their specific affiliations and contributions and whether they were compensated for those contributions.
3. All journals must disclose all pertinent relationships of all authors with any for-profit companies, and must publish all funding sources for each article.
4. Journal editors must seriously consider funding sources and authors’ disclosed financial conflicts of interest and financial relationships when deciding whether to publish a study or review.
5. For-profit companies that sponsor biomedical research studies should not be solely or primarily involved in collecting and monitoring of data, in conducting the data analysis, and in preparing the manuscript reporting study results. These responsibilities should primarily or solely be performed by academic investigators who are not employed by the company sponsoring the research.
6. All journals must require a statistical analysis of clinical trial data conducted by a statistician who is not an employee of a for-profit company.
7. Any author who fails to disclose financial relationships or other conflicts of interest, or who allows his or her name to be used for work that he or she did not actually perform, must be reported to the appropriate authority (ie, medical school dean or department chair) or appropriate oversight body. If an article in which this occurs is published, the offending author must then submit a letter to the editor, in which he or she provides full disclosure and apologizes for the infraction to the readers of the journal. Depending on the nature and severity of the issue, the author may be banned from publishing articles in that journal.
8, Any peer reviewer who provides any confidential information, such as a manuscript under review, to any third parties, such as for-profit companies, or who engages in other similar unethical behavior, also should be reported to the appropriate authority (eg, medical school dean) or oversight body, and should be banned from reviewing and publishing articles in that journal.
9. Any editor who knowingly allows (or is party to allowing) for-profit companies to manipulate his or her journal must be relieved of the editorship.
10. To maintain a healthy distance from industry influence, professional organizations and providers of continuing medical education courses should not condone or tolerate for-profit companies having any input into the content of educational materials or providing funding or sponsorship for medical education programs.
11. Individual physicians must be free of financial influences of pharmaceutical and medical device companies including serving on speaker’s bureaus or accepting gifts.
The manipulation of pharmaceutical studies is wrong and must be corrected.