Are you involved in multi-national clinical research in North America? Are you wondering whether – and where – you have to register a clinical trial? And why?

Why should we register this clinical trial?

Let’s address the ‘why’ question first. Registration is internationally recognized as a scientific, ethical and moral responsibility that “will improve research transparency and will ultimately strengthen the validity and value of the scientific evidence base”. For instance, the Declaration of Helsinki states that “every clinical trial must be registered in a publicly accessible database before recruitment of the first subject”.

The World Health Organization (WHO) identified several benefits to registration which include:

  • more informed health care decisions;
  • prevention against publication bias and selective reporting;
  • prevention of unnecessary duplication of research;
  • promotion of participant recruitment;
  • promotion of effective collaboration among researchers; and
  • improvements in the quality of clinical trials.

Further, the International Committee of Medical Journal Editors (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.” Thus if the results of a clinical trial are to be published, prior registration of the trial is generally a prerequisite for consideration by medical journals.

Which registry should we use?

When selecting a clinical trial registry for research being conducted across North America, we encounter something of a dilemma as 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.”
Although the Canadian government – through Health Canada – has launched its own (non-mandatory) Clinical Trials Database, it clearly states that this is not a clinical trial registry. The Canadian Clinical Trials Database is thus not recognized by the ICMJE. Nor is there currently any recognized registry for clinical trials being conducted in Mexico. In fact, as of April 4, 2014 only 14 registries were recognized by the ICMJE.

This leaves Canadian and Mexican regulatory affairs professionals with no option other than to register in ClinicalTrials.gov in order to meet the ICMJE requirement.

Consent form requirements for studies conducted in the US

If the clinical trial is also being conducted in the US (for example under an IND), then the following specific language must be included in the local country version of the informed consent documentation (ICD/ICF):

‘‘A description of this clinical trial will be available on ClinicalTrials.gov, as required by U.S. Law. This Web site will not include information that can identify you. At most, the Web site will include a summary of the results. You can search this Web site at any time.’’

Under 21 CFR § 50.25(c), the U.S. Food and Drug Administration (FDA) requires that the statement above be included in the ICD/ICF for all ‘applicable clinical trials’ initiated on or after March 7, 2012. This exact statement is required regardless of whether the Research Participant is in the US, Canada, Mexico, or another country.
It was made very clear in response to Comment 10 if the US Federal Register, Volume 76, Number 2 (pages 256-270) dated January 4, 2011, that the inclusion of this specific language was required regardless of the “local community, subject population, type of study, or, in non-U.S. Trials”.

More information regarding the “applicable clinical trials” covered under this regulation can be found here.

Whose responsibility is it to determine if a study requires registration?

It is the responsibility of sponsors and investigators to determine whether a specific study qualifies as an ‘applicable clinical trial. The US Federal Register, Volume 76, Number 2 (pages 256-270) dated January 4, 2011 stated (in response to Comment 20) that:

“It is the responsibility of the sponsors and investigators to determine if their clinical trial meets the definition of an applicable clinical trial and to ensure compliance with the most current applicable statutory and regulatory requirements.”

In summary

Registration of clinical trials is not only a scientific, ethical and moral duty, but also prerequisite for consideration by medical journals.

If a clinical trial meets the US criteria for an ‘applicable clinical trial’, it must be listed in ClinicalTrials.gov regardless of whether it is also registered in a primary register of the WHO International Clinical Trials Registry Platform (ICTRP). Failure to register in ClinicalTrials.gov would constitute non-compliance with US regulations.

If a clinical trial is being conducted in another country or area, we recommend that it also be registered in any available local registry such as the Health Canada Clinical Trials Database.

The Veritas IRB Inc. Editorial Board

The Veritas IRB Editorial Board covers questions of research ethics, clinical trial conduct, and human research participant protection primarily for sponsors, CROs and investigators/researchers. // Le blogue de Veritas IRB aborde des questions de l'éthique de la recherche, de la bonne conduite des essais cliniques, et de la protection des participants à la recherche dans une perspective axée sur les promoteurs de la recherche, les organismes de recherche sous contrat (ORCs ou CROs), et les chercheurs.