Clinical Trials Registration: Will Your Study Be Publishable?

In 1997, the US Congress passed the Food and Drug Administration Modernization Act, which required the US Department of Health and Human Services, through the National Institutes of Health, to establish a registry of clinical trials for both federally and privately funded trials of experimental treatments for serious or lifethreatening diseases. In addition to this US statutory requirement, the International Council of Medical Journal Editors (ICMJE) adopted a policy in 2005 to require that studies be registered in order to be eligible for publication. A trial that requires registry was initially defined as one that must have at least one prospectively assigned concurrent control or comparison group to trigger the requirement for registration. The most widely used site in the United States is http:// www.clinicaltrials.gov, although others meet the minimal requirements for registration. As indicated in the Information for Contributors, Journal of Clinical Oncology (JCO) will accept registration in any public database that meets the WHO minimal data set. The ICMJE Web site (FAQ section) lists the following registries as fully compliant: http://www.actr.org.au, http://www.umin.ac.jp/ctr/index.htm, and http://www.trialregister.nl, http://www.clinicaltrials.gov, and http:// www.ISRCTN.org. Updates on the evolution of the clinical trials registration process can be found on the ICMJE Web site (http:// www.icmje.org). A 2007 online JCO editorial alerted readers to a broadened definition of which trials required registration. Although pharmacokinetic and preliminary studies were initially excluded, the ICMJE recently expanded the definition to include the WHO definition of a trial that requires registration: “A clinical trial is any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes. Interventions include but are not restricted to drugs, cells and other biologic products, surgical procedures, radiologic procedures, devices, behavioral treatments, process-of-care changes, preventive care, and so on” (http://www.who.int/ictrp/en/). The ICMJE required this expanded registration as of July 1, 2008. Importantly, the ICJME has advised that reporting of significant results from a trial in a registry of greater than 500 words may be considered prepublication, thereby reducing a later manuscript’s likelihood of primary publication. Currently, JCO requires that “any clinical trial for which patient enrollment begins on or after November 1, 2006, must be registered. Authors will have 6 months from the first patient enrollment to register the trial, but registration before enrollment is recommended.” The editors have recognized that, even under our older definition of a trial that requires registration, studies that are now just being submitted to JCO will begin to fall under these restrictions. Registration is the responsibility of the investigator, and this must be recognized at the activation of a trial. Although a 21-day grace period is allowed after the first patient is enrolled, retrospective registration after the grace period is not allowed, which may render many trials ineligible for publication. We are publishing this editorial update as a service to authors, to ensure that both investigators and patients who participate in their trials will have their efforts rewarded by full and timely publication.