A group of 12 editors from "prestigious medical journals" on Wednesday announced that they will refuse to publish research from drug companies' clinical trials unless the studies are part of a national registry accessible to the public at no charge -- "a step designed to ferret out unpublished studies that find medications to be ineffective or dangerous," the Washington Post
reports. According to the Post
, the initiative from the International Committee of Medical Journal Editors
will create a "potent incentive" for companies to register their trials "well before anyone knows whether a study will turn out positive" (Vedantam, Washington Post
, 9/9). While the plan did not specify an existing registry, the editors said it would have to be electronically searchable and managed by a not-for-profit organization. Each study on the registry would be described in detail, "from its primary and secondary outcome measures to its funding source," and would be registered at or before patient enrollment, the Wall Street Journal
reports (Whalen, Wall Street Journal
, 9/9). According to the New York Times
, the registry must include the purpose of the study, "how its goals were initially defined," its commencement date, its anticipated length and its sponsor company. Companies will not be required to register Phase I preliminary trials, which are used to examine biological activity and toxicity. The editors said that the only current database template that would meet their requirements is the ClinicalTrials.gov
site operated by NIH
's National Library of Medicine
(Meier, New York Times
, 9/9). The requirement would apply to any trials that begin after June 1, 2005 (Washington Post
, 9/9). Trials that were in progress before that date must be registered by September 2005 to be considered for publication.
Clinical Trials Controversy
According to the Times, the "major policy shift" was spurred by a "furor about clinical trials" following recent claims that drug companies have sought to suppress negative trial data concerning the use of antidepressants in children (New York Times, 9/9). GlaxoSmithKline last month agreed to settle a lawsuit filed by New York Attorney General Eliot Spitzer (D) that will require the company to post all of its clinical trial results online by the end of 2005. The lawsuit alleged that GSK withheld data from clinical trials that indicated the antidepressant Paxil is no more effective in adolescents and children than a placebo and in some cases is more likely than a placebo to cause suicidal thoughts. Merck and Eli Lilly have also recently announced plans to register their clinical trials on their own Web sites. In addition, Spitzer on Tuesday said Forest Laboratories had responded to an investigation into its trials by agreeing to create an online registry and post summaries of all of its studies conducted after Jan. 1, 2000, as well as some earlier studies. Under the agreement, Forest is required to post its summaries by Dec. 31, 2005.
NIH last week announced that the agency planned to make available at no cost to the public the results of all NIH-funded research six months after the work is published in a scientific journal. The proposal, which NIH has been considering for more than a year, would require federally funded researchers to submit their papers to the agency after they have been accepted for publication and edited by a journal. Meanwhile, the Pharmaceutical Research and Manufacturers of America on Tuesday presented plans to launch on Oct. 1 a database that would publish clinical trial results within a year of their conclusion; feature only summaries of unpublished studies; exclude some data, such as early-stage studies and unfinished trials; include trials not published in medical journals; and contain only trials completed after Oct. 1, 2002 (Kaiser Daily Health Policy Report, 9/8). Catherine DeAngelis, editor of the Journal of the American Medical Association, said any registry run by the drug industry would not be adequate, and she called the idea of a voluntary registry "absolutely ludicrous." She added that it is important to register trials from their beginning so that experts can see what happened to studies that were not completed or submitted for publication (Burling, Philadelphia Inquirer, 9/9).
Journal EditorialsAdvertisementEditors' Announcement
In an editorial to be released on Thursday, the participating journals' editors write, "When research sponsors or investigators conceal the presence of selected trials, these studies cannot influence the thinking of patients, clinicians, other researchers and experts who write practice guidelines or decide on insurance-coverage policy. If all trials are registered in a public repository at their inception, every trial's existence is part of the public record" (Wall Street Journal, 9/9). The editorial continues, "Honest reporting begins with revealing the existence of all clinical studies, even those that reflect unfavorably on a research sponsor's product," and "selective reporting ... distorts the body of evidence available for clinical decision-making." An accompanying editorial written by Dr. Drummond Rennie, deputy editor of JAMA and one of a small number of researchers who have long advocated for greater clinical trial disclosure, states, "One consequence of this lack of reporting is a persistent bias in favor of ... the newer and more expensive treatments. Another consequence is that harmful effects found in unpublished trials disappear without a trace, since [FDA] has no mandate to report them to the public" (New York Times, 9/9). The editors added that trial participants "who risk their lives to be in clinical trials have a right to see the work made public," the Inquirer reports (Philadelphia Inquirer, 9/9). The editorial continues, "Altruistic individuals volunteer for research because they trust that their participation will contribute to improved health for others. In return for the altruism and trust that make clinical research possible, the research enterprise has an obligation to conduct research ethically and to report it honestly" (Rowland, Boston Globe, 9/9).
"When you do something as bold as to propose to doctors that they do a certain thing to a patient, you want to be sure that you're basing that recommendation on all the evidence and not simply the evidence that finds its way into print," Hal Sox, editor of the Annals of Internal Medicine
, said at the announcement (Philadelphia Inquirer
, 9/9). The editors said they hope more journals eventually join them in the policy shift but added that they believe "preserving the opportunity to publish a positive study in a prominent journal, which can greatly boost the visibility of a new drug, will be a juicy enough carrot" to encourage registration, the Post
reports. While companies could still decide not to publish negative trial results, Gregory Curfman, executive editor of the New England Journal of Medicine
, said, "Registration in and of itself is a very big step. Even if there aren't results out there, the very fact it is known this trial was conducted is a very big step forward -- it becomes much harder to bury a trial away" (Washington Post
, 9/9). NEJM
Editor in Chief Jeffrey Drazen added that researchers could avoid being involved in studies they knew would never reach the top journals (AP/Long Island Newsday
PhRMA spokesperson Jeff Trewhitt said several companies are already registering their trials voluntarily and some firms "may have reservations about divulging proprietary information in clinical tests that are in very early phases. ... [I]n the end it is their decision" (Washington Post, 9/9). Dr. Alan Breier, chief medical officer of Lilly, said that while his company had not had time to review the editors' plan, he believed his company's trial disclosure proposal would adequately address many of the concerns raised by the editors. Pfizer spokesperson Stephen Lederer declined to comment on the editors' announcement but said widespread trial registration "is a rapidly moving picture" (New York Times, 9/9) PhRMA spokesperson Alan Goldhammer said his group would examine the new policy but remained committed to its own plan (AP/Long Island Newsday, 9/9). Arthur Caplan, director of the Center for Bioethics at the University of Pennsylvania, said a national registry "makes eminent sense," but, he added, "it is hard for a group of private journals to change the industry" (New York Times, 9/9).
The editors' announcement "was timed to coincide" with a hearing on Thursday of the House Subcommittee on Oversight and Investigations where drug company executives, FDA officials and representatives from the American Medical Association are expected to be questioned about antidepressants and safety-disclosure issues, the Journal reports. In addition, Democrats in the House and Senate are preparing to introduce within the next two weeks separate bills that would expand the ClinicalTrials.gov registry and strengthen disciplinary measures for companies who do not register their studies. A bill co-sponsored by Sens. Edward Kennedy (D-Mass.) and Christopher Dodd (D-Conn.) and others would require that trials be registered before they begin. The bill, along with legislation written by Reps. Henry Waxman (D-Calif.) and Edward Markey (D-Mass.), would also require disclosure of all trial results. Both bills would give FDA the power to penalize companies that do not comply with the rules and would block NIH from issuing grants to researchers who do not follow the policy (Wall Street Journal, 9/9). AMA has also been working with HHS to develop legislation that would create a mandatory, regulated registry of trials. Under the AMA proposal, trials would need to be registered before receiving approval from institutional review boards, which is required for all studies involving human subjects. PhRMA has previously said it believes legislation on the matter is unnecessary (Kaiser Daily Health Policy Report, 9/8).
Trewhitt on Wednesday declined to specifically comment on the legislation, but said, "We want to work with members of Congress to make sure that we're doing what's best for patients." Markey, who is expected on Thursday to introduce his bill, said, "Every student starting school this fall knows they can't pick and choose which test will count and which won't. Likewise, drug companies can't decide which trials to disclose and which to hide from the public." He added, "I understand the concern of some companies that if they report an adverse result their stock might suffer. The alternative is that patients suffer when doctors prescribe in the dark" (Boston Globe, 9/9).
NPR's "All Things Considered" on Wednesday reported on the medical journal editors' proposal. The segment includes comments from DeAngelis and Waxman (Prakash, "All Things Considered," NPR, 9/8). The complete segment is available online in RealPlayer.
Back to other news for September 9, 2004
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