What is the requirement?
The International Committee of Medical Journal Editors (ICMJE) announced that in order for clinical trial results to be considered for publication in journals that adhere to ICMJE standards, all clinical trials that start recruiting on or after July 1, 2005 must be registered with a public registry before the enrollment of the first patient. Ongoing trials not registered at inception will be considered by the ICMJE for publication if they are registered before September 13, 2005. Details of this requirement are described at the International Committee of Medical Journal Editors web site.
Note: This is not a regulatory requirement related to human subjects research.
What is the purpose of this requirement?
As described on the ICMJE web site, the Committee’s purpose is “to promote the public good by ensuring that everyone can find key information about every clinical trial whose principal aim is to shape medical decision-making,” and to foster conditions in which decisions about care “rest on all of the evidence, not just the trials that authors decided to report and that journal editors decided to publish.”
How is “clinical trial” defined?
The ICMJE Web site defines a clinical trial as “Any research project that prospectively assigns human subjects to intervention and comparison groups to study the cause-and-effect relationship between a medical intervention and a health outcome.”
The phrase “medical intervention” suggests that this requirement applies only to biomedical clinical trials. Is that correct?
No. “Medical intervention” is defined as any intervention used to modify a health outcome. According to the ICMJE, this term includes “drugs, surgical procedures, devices, behavioral treatments, process-of-care changes, and the like.”
Does it apply only to industry-sponsored clinical trials?
No. It does not matter who the sponsor is or whether there is an external sponsor.
Are there any exceptions?
Yes. ICMJE’s goal is to register “clinically directive” trials – “trials whose primary purpose is to affect clinical practice.” Excluded are trials whose “primary goal is to assess major unknown toxicity or determine pharmacokinetics.”
Note this important advice from the ICMJE: If in doubt about whether a trial is “clinically directive,” register it.
Where/what are the registries?
The ICMJE describes the characteristics of an acceptable trial registry and the required minimal data for each trial. One of the registries that meets the ICMJE descriptive criteria is ClinicalTrials.gov, a service of the NIH, developed by the National Library of Medicine. To find out more about the Protocol Registration System (PRS) at ClinicalTrials.gov, visit the PRS Information web site.
Who does the registration?
The PI is responsible for ensuring that registration requirements are met. Even though some sponsors will do the actual registration work for the PIs, it is still the PI’s responsibility to ensure that the registration has been accomplished. Before enrolling subjects, every PI should ask the trial’s sponsor, “Is this clinical trial fully registered?” Assuming an affirmative response, investigators should personally check the registry indicated by the sponsor to ensure that all ICMJE Minimal Registration Data Set elements are included.
- NIH-sponsored trials should be registered by the Institute that is funding the research.
- Industry-sponsored trials (industry-written protocol) should be registered by the sponsor.
- Investigator-initiated trials (for which industry has supplied drug or grant funds) should be registered by the PI.
- Trials for which PIs hold their own INDs or IDEs should registered by the PI.
- Multi-site trials should be should be coordinated among the sites and registered by the “lead sponsor” so that ClinicalTrials.gov does not receive multiple registrations for the same trial.