Over the past several years, leaders in the field of medical research and publishing have developed the CONSORT (Consolidated Standards of Reporting Trials) guidelines and the Uniform Requirements for Manuscripts Submitted to Biomedical Journals to ensure that clinical trial methods and reporting meet certain uniform standards. Two studies presented at the most recent International Congress on Peer Review in Biomedical Publication (and subsequently published last month in the Journal of the American Medical Association [2002; 287:2835–2838]), however, found that many authors are not following the guidelines.
In one, Drummond Rennie, MD, JAMA's Deputy Editor, and Professor of Medicine at the University of California, San Francisco (UCSF), and Veronica Yank, a medical student at UCSF, found that in nine percent of the clinical trials published after 1997 in Annals of Internal Medicine, BMJ, JAMA, Lancet, and the New England Journal of Medicine, the authors failed to mention either informed consent or ethics committee approval.
This low number is despite a previous paper published in 1997 by Dr. Rennie that brought the problem to the editorial community's attention.
Dr. Rennie said it is clear that the situation is improving but still inadequate.
“The earlier paper showed a terrible mess, and upset some of the journals”—and provoked them to change their policies, Dr. Rennie said in a subsequent interview this spring.
Based on the new data, Dr. Rennie said, it is clear that the situation is improving but still inadequate. Before 1997, 26 percent of the authors failed to mention informed consent; now that number is down to 18 percent.
The change is even more dramatic when looking at the number of researchers who failed to include information about ethics review board approval; in the current study 19 percent of papers lacked such information, down from 31 percent in the 1997 study.
Although it may initially seem unnecessary to require inclusion of this information in manuscripts because both ethics committee approval and informed consent are required by law, Dr. Rennie notes that such clear statements in published articles emphasize the importance and helps to prevent lapses.
“To me it would be almost incredible that a trial should have been done without proper informed consent, except that Johns Hopkins discovered just such a case last summer,” said Dr. Rennie, referring to a collaborative project between a Johns Hopkins researcher and researchers in India, in which the scientists failed to obtain proper consent.
“It is so important to put [the information] down, because it shows, amongst many other things, that the investigators, and the institution, and the journal think that the ethical aspects of this are perhaps the most important thing about the trial,” Dr. Rennie concluded.
Disclosure of Financial Information
In a related study, Anu R. Gupta, MD, a Robert Wood Johnson Clinical Scholar at the Yale School of Medicine in New Haven, CT, and her collaborators examined how frequently authors described the role of sponsors in the design, data analysis, and manuscript preparation of randomized controlled trials as is required by the Uniform Requirements.
Of the 268 randomized controlled trials published between April 1, 1999 and March 31, 2001 in Annals of Internal Medicine, BMJ, JAMA, Lancet, and New England Journal of Medicine, 100 were supported by industry. Nearly half (48%) included an author disclosure, and 31 percent failed to provide any disclosure information, and in 21 percent of the reports there was a presumed conflict due to the author's address affiliation with the industry sponsor.
Significantly, though, only those papers published in Annals included specific information about the actual substantive role of the industry sponsor in the trial—despite the requirements for such information in the Uniform Requirements.
Writing in the March/April 2002 issue of Health Affairs, Frank Davidoff, MD, the former editor of Annals of Internal Medicine, describes the events and reasoning that led up to such strict standards. “Having such information, as Annals editors, reviewers, and statisticians now do, helps in judging both internal and external validity of clinical studies, in much the same way as knowing sampling strategy, sample size, and study population characteristics. Moreover, in principle, disclosing the role of financial supporters in the methods section of clinical journals benefits readers. It is, after all, the interpretation of published articles that converts study reports into clinical practice.”
Before 1997 26% of the authors failed to mention informed consent; now that number is down to 18%.
Therefore, if a trial sponsor is exerting undue influence on the experimental design, or on the wording of the manuscript, readers should have that information available as they evaluate the study in relation to their own work.
“In the ideal world,” Dr. Gupta said, “people wouldn't want industry to be involved in designing the trials, collecting or analyzing data, or preparing the manuscript.” Instead industry would just give money to independent researchers, with no strings attached.
However of the nine randomized controlled trials examined in her study that disclosed the level of the industry sponsor's involvement, only five indicated that the sponsor was involved in trial design or analysis.
“Five out of nine could just be an outlier, or it could be representative of what is there, “ she said. “But with so few authors disclosing the sponsor's role, the data just isn't available to say how involved the sponsors are.
And that, she thinks, is a situation that needs to be rectified. After all, if industry isn't unduly influencing the trials then people's fears can be allayed.
If on the other hand, the problem of conflict of interest is as rampant as anecdotal information suggests, then the problem can be addressed, she said. “But without information, we are not able to do either of those things.”
32 Pages of ASCO News in This Month's Supplement!
OT's extensive coverage of news from this year's ASCO Annual Meeting, which started in last month's issue, continues this month in our fourth annual OT ASCO Reporter, which is included as a supplement to this issue. This Special Edition includes summaries of key studies, as well as interviews with and commentary by ASCO leaders and other experts.