Clinical Trial Registration
Briefly, the ICMJE requires, and recommends that all medical journal editors require, registration of clinical trials in a public trials registry at or before the time of first patient enrollment as a condition of consideration for publication. Editors requesting inclusion of their journal on the ICMJE website list of publications that follow ICMJE guidance should recognize that the listing implies enforcement by the journal of ICMJE’s trial registration policy.
The ICMJE defines a clinical trial as any research project that prospectively assigns people or a group of people to an intervention, with or without concurrent comparison or control groups, to study the cause-and-effect relationship between a health-related intervention and a health outcome. Health-related interventions are those used to modify a biomedical or health-related outcome; examples include drugs, surgical procedures, devices, behavioural treatments, educational programs, dietary interventions, quality improvement interventions, and process-of-care changes. Health outcomes are any biomedical or health-related measures obtained in patients or participants, including pharmacokinetic measures and adverse events. The ICMJE does not define the timing of first patient enrollment, but best practice dictates registration by the time of first patient consent.
The ICMJE accepts registration in any registry that is a primary register of the WHO International Clinical Trials Registry Platform (ICTRP) or in ClinicalTrials.gov, which is a data provider to the WHO ICTRP. The ICMJE endorses these registries because they meet several criteria. They are accessible to the public at no charge, open to all prospective registrants, managed by a not-for-profit organization, have a mechanism to ensure the validity of the registration data, and are electronically searchable. An acceptable registry must include the minimum 20-item trial registration dataset (http://prsinfo.clinicaltrials.gov/trainTrainer/WHO-ICMJE-ClinTrialsgov-Cross-Ref.pdf or www.who.int/ictrp/network/trds/en/index.html) at the time of registration and before enrollment of the first participant. The ICMJE considers inadequate trial registrations missing any of the 20 data fields or those that have fields that contain uninformative information. Although not a required item, the ICMJE encourages authors to include a statement that indicates that the results have not yet been published in a peer-reviewed journal, and to update the registration with the full journal citation when the results are published.
The purpose of clinical trial registration is to prevent selective publication and selective reporting of research outcomes, to prevent unnecessary duplication of research effort, to help patients and the public know what trials are planned or ongoing into which they might want to enroll, and to help give ethics review boards considering approval of new studies a view of similar work and data relevant to the research they are considering. Retrospective registration, for example at the time of manuscript submission, meets none of these purposes. Those purposes apply also to research with alternative designs, for example observational studies. For that reason, the ICMJE encourages registration of research with non-trial designs, but because the exposure or intervention in non-trial research is not dictated by the researchers, the ICMJE does not require it.
Secondary data analyses of primary (parent) clinical trials should not be registered as separate clinical trials, but instead should reference the trial registration number of the primary trial.
The ICMJE encourages posting of clinical trial results in clinical trial registries but does not require it. The ICMJE will not consider as prior publication the posting of trial results in any registry that meets the above criteria if results are limited to a brief (500 word) structured abstract or tables (to include patients enrolled, key outcomes, and adverse events).
The ICMJE recommends that journals publish the trial registration number at the end of the abstract. The ICMJE also recommends that, whenever a registration number is available, authors list this number the first time they use a trial acronym to refer either to the trial they are reporting or to other trials that they mention in the manuscript.
Editors may consider whether the circumstances involved in a failure to appropriately register a clinical trial were likely to have been intended to or resulted in biased reporting. If an exception to prospective registration is made, trials must be registered and the authors should indicate in the publication when registration was completed and why it was delayed. Editors should publish a statement indicating why an exception was allowed. The ICMJE emphasizes that such exceptions should be rare, and that authors failing to prospectively register a trial risk its inadmissibililty to our journals.
Next: Preparing for Submission (in Manuscript Preparation)