In accordance with ICMJE recommendations (International Committee of Medical Journal Editors), Randomized Controlled Trials (RCTs) (but not other trial designs) must be prospectively registered (before the trial starts) in a WHO accredited trial registry such as clinicaltrials.gov.
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. (ICMJE)
Purely observational studies (those in which the assignment of the medical intervention is not at the discretion of the investigator) do not require registration. JMIR does not currently enforce this rule for non-randomized studies, i.e. only randomized studies require registration.
JMIR authors should be reminded that mobile and web-based interventions as well as devices are usually targeting behavioural or other outcomes, and must usually be registered. This is not something we invented, but a consensus of medical editors and the research community.
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.(ICMJE)
For reports of clinical trials, please mention the ClinicalTrials.gov registration identifier, the International Standard Randomized Controlled Trial Number (ISRCTN), or a comparable trial identifier at the end of the abstract ("Trial Registration: ClinicalTrials.gov NCT123456"), as well as when you first mention the trial in the manuscript. Protocols do not have to be registered although we highly recommend it and the (separate) results paper of the study can only be published if it carries a registration identifier and if it was prospectively registered (before enrolment of participants).
When mentioning related trials (e.g. in the Introduction or Methods section) the trial registration number should also be added in brackets.
ICMJE member journals require, as a condition of consideration for publication, registration in a public trials registry at or before the onset of patient enrollment. This policy applies to any trial which started enrollment after July 1, 2005.
JMIR authors must add an explanation to the methods section of their manuscript if a RCT meeting these criteria has not been registered. The JMIR editor reserves the right to reject any paper without trial registration without any further consideration or peer-review, or to add a "Notice of Editorial Concern" (see below).
If authors neglect prospective registration, this may render the paper unpublishable in most journals.
JMIR can offer the following exceptions:
- the paper can be transferred to JMIR Res Protoc or JMIR Formative Res or, as formative/pilot/feasibility studies do not require registration
- "If the purpose is to examine the effect only on the providers rather than patients (for example, provider knowledge or attitudes), then registration is not necessary" (ICMJE). JMIR journals also recognize graduate/undergraduate (medical, psychology etc) students (but not elementary/middle/high school students) or other volunteer subjects as a valid exception, although when in doubt, authors should err on the side of caution and register the trial prospectively
- if a protocol has been published (for example submitted to JMIR Res Protoc) before enrolment, then we may also waive the trial registration mandate, because publication of the protocol meets all of the purposes listed above regarding transparency and prevention of "outcome creep" (see also Why should I publish my protocol or grant proposal?)
- in some cases we may accept letters from the IRB/REB confirming that the protocol/design of the submitted study is identical with what the IRB/REB assessed when providing approval before the trial started
- JMIR is interested in reducing publication bias, thus, as recommended by the ICMJE, JMIR editors may grant exceptions on a case-by-case basis, if the potential for bias was low. However, authors must explain why the trial was not prospectively registered, and need to register it retrospectively. This should be explicitly mentioned in the methods part of the paper. The editor reserves the right to add a notice of editorial concern to the paper (see below). The ICMJE recommendation on exceptions reads as follows:
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 [retrospectively] 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 admissibililty to our journals.
Notice of Editorial Concern
Starting in 2017, JMIR will add a "Notice of Editorial Concern" to any paper where the RCT has not been prospectively registered (i.e. the editor made an exception, as specified above under point 5).
Sample text (to be published underneath the "Conflict of Interest" section):
Notice of editorial concern / Editorial notice: This randomized study was only retrospectively registered, explained by authors with (insert reasons here, e.g. "technical problems"). The editor granted an exception from ICMJE rules mandating prospective registration of randomized trials, because the risk of bias appears low and the study was considered formative, guiding the development of the application [or other reasons for the exception, as argued by the authors]. However, readers are advised to carefully assess the validity of any potential explicit or implicit claims related to primary outcomes or effectiveness, as retrospective registration does not prevent authors from changing their outcome measures retrospectively.
To be clear, a RCT still needs to be retrospectively registered if an exception under point 5 is granted, and the trial registration number needs to be mentioned in the abstract. "Retrospectively" means any registration that occurred after the first participants was enrolled.