New journal policy regarding registration of clinical trials

When patients consent to participate in a clinical study, a principal motivation for many is to contribute to medical knowledge. From this foundation of trust, a sine qua non for clinical investigation, several questions arise: Do patients have a right to know that the results of the study in which they participate will eventually be available to medical researchers and the public at large? If a clinical trial is initiated but later canceled, how do physicians and patients learn why? When a trial fails to demonstrate efficacy and its results are never published, should that information be accessible, and to whom? Finally, if a trial demonstrates that a medication causes harm, who has the right to know, and when? These questions have driven much of the recent public debate about compulsory clinical trials registration. The movement to register all clinical studies was the subject of a policy statement issued in September 2004 by members of the International Committee of Medical Journal Editors (ICMJE) (1), a committee of editors of 11 general medical journals (New England Journal of Medicine, Journal of the American Medical Association, Lancet, New Zealand Medical Journal, Norwegian Medical Journal, Canadian Medical Association Journal, Annals of Internal Medicine, Croatian Medical Journal, Nederlands Tijdschrift voor Geneeskunde, Journal of the Danish Medical Association, and Medical Journal of Australia). The ICMJE declared that, as of July 1, 2005, they will accept for publication only those reports of clinical trials that have been preregistered—before enrollment of the first patient—with one of several publicly accessible, free-ofcharge Web sites. At approximately the same time, members of the Cochrane Collaboration met in Ottawa to develop a statement calling for even broader requirements in the area of clinical trials registration (2). Finally, clinical trials registration is the topic of bipartisan-sponsored legislation currently under debate on Capitol Hill. This legislation is known as the Fair Access to Clinical Trials (FACT) Act (3). Proponents of clinical trials registration argue that this measure is essential not only to ensure accuracy in the publication of studies’ results, but also to guarantee access (at appropriate times) to all interested parties: clinicians, institutional review boards (IRBs), sponsors, other investigators—and patients. Recent experiences with the selective serotonin release inhibitors in childhood depression (4,5) and with cyclooxygenase 2 inhibitors (6,7) demonstrate unequivocally that, under the status quo, information available to some parties—typically selected researchers and pharmaceutical houses—is not available to most physicians or patients. At best, this closed information loop leads to redundancy in the types of clinical trials undertaken and lack of access to data about promising therapies. At worst, undisclosed trial results have the potential to cause harm to patients that would be preventable in a more open structure for clinical trials reporting. At present, detailed information about the lifetime batting average of the most obscure major league baseball player is easier to access than are reliable data about even the very existence of some research conducted in the name of biomedical science. In the information age, medicine should do better. Through the years, several attempts have been made to remedy the “secrecy” with which some trials are conducted. In 1997, the Food and Drug Administration (FDA) Modernization Act created a voluntary registry for clinical trials: www.clinicaltrials.gov. This registry, maintained by the National Library of Medicine, contains information related to trial design, eligibility criteria, investigators, and participating sites. Unfortunately, this Web site does not include information about the most important aspect of trials: their results. Moreover, because the law makes no provision for enforcement, www.clinicaltrials.gov registers only a fraction of all trials. Finally, because the statute that created the database applies only to trials conducted under Investigational New Drug licenses—required only for clinical trials conducted in the US—the database has a John H. Stone, MD, MPH: Johns Hopkins University, Baltimore, Maryland (member, American College of Rheumatology Committee on Journal Publications); Michael D. Lockshin, MD: Hospital for Special Surgery, Weill Medical College of Cornell University, New York, New York (Editor, Arthritis & Rheumatism); Patricia P. Katz, PhD, Edward H. Yelin, PhD: University of California, San Francisco (CoEditors, Arthritis Care & Research). Address correspondence to John H. Stone, MD, MPH, Vasculitis Center, JHAAC Room 1B23, Johns Hopkins University, 5501 Hopkins Bayview Circle, Baltimore, MD 21224. E-mail: jstone@jhmi.edu. Submitted for publication May 24, 2005; accepted May 24, 2005. Arthritis & Rheumatism (Arthritis Care & Research) Vol. 53, No. 4, August 15, 2005, pp 484–487 DOI 10.1002/art.21339 © 2005, American College of Rheumatology