The requirements of the FDA and the US NIH related to the registration and reporting of clinical trials have been changed. Effective January 18, 2017, the FDAAA 801 mandated that all “Applicable Clinical Trials” (defined here and also see below) be registered on clinicaltrials.gov. The mandate also required summary results reported on clinicaltrials.gov no later than 12 months after the last patient has been followed up for the primary outcome.
At Unity Health Toronto (“Unity Health”) we are committed to the complete and unbiased reporting of all research results. We believe that the results of all trials conducted at Unity Health should be analyzed and published in a timely manner. We have established reporting requirements for all interventional trials. Please refer to our institutional guidelines posted on the intranet.
This page provides Q&A to help you understand general information about trial registration and results reporting as well as the changes with the FDA and NIH rules.
Why are we implementing the guidelines across Unity Health Toronto (St. Michael’s Hospital, St. Joseph’s Health Centre, Providence Healthcare)?
- Patients who have agreed to participate in clinical trials expect the results to be analyzed and communicated in a timely manner. Registering clinical trials and providing timely updates including results allows the public to have access to ongoing clinical trials and summary results. This action also reduces publication bias and duplication of research efforts.
- As a public institution we are accountable for our use of public funds and committed to transparency by reporting all trial results, or reporting explicitly why results have not been published.
- The International Committee of Medical Journal Editors (ICMJE) requires trial registration as a condition of the publication of research results generated by a clinical trial.
- Section 801 of the Food and Drug Administration Amendments Act (FDAAA 801) requires Responsible Parties to register and submit summary results of clinical trials with ClinicalTrials.gov. The law applies to certain clinical trials of drugs (including biological products) and medical devices.
Who is responsible for registering the trial?
- Industry-sponsored trials: Where there is a contract between the industry Sponsor, Unity Health or any of its sites, and the PI, then the industry sponsor should register the trial. Before enrolling study subjects, every PI should ensure the industry Sponsor has registered the trial.
- Investigator-initiated trials:
- The lead PI of an investigator-initiated trial (“Sponsor-Investigator”) is responsible for study registration, even if a corporate partner provides the study drug, device and/or grant funds.
- Where the lead PI is at Unity Health or any of Unity’s sites and trial funding is held and administered through Unity Health, the PI is responsible for registration through the affiliated institution.
- Multi-site trials: Where Unity Health or any of Unity Health’s sites is a sub-contractor and the lead PI is not at Unity Health , registration should be coordinated among the study sites and registered by the “lead sponsor” or lead PI to avoid multiple registrations.
How early should I register a clinical trial?
- The ICMJE requires, and recommends that all medical journal editors require registration of all interventional clinical trials in a public trials registry at or before the time of first patient enrollment as a condition of consideration for publication (see more information).
- The World Medical Association (WMA) Declaration of Helsinki states “Every research study involving human subjects must be registered in a publicly accessible database before recruitment of the first subject.”
- FDAAA 801 requires ACT to be registered within 21 days of enrollment of the first participant.
- Although ClinicalTrials.gov allows registration of a non-ACT study at any time (even after it has started, has closed to recruitment, or has been completed; see more information), this is not recommended given the requirements above.
Information specific to clinicaltrials.gov
Unity Health accepts any of the registries that are approved by the ICMJE and WHO. The additional information about ClinicalTrials.gov is outlined below because the U.S. Department of Health and Human Services (HHS) has specific requirements for registration, updates and summary results reporting.
How do I get a user account for clinicaltrials.gov?
- If you wish to register your trial through clinicaltrials.gov and need a user account, please contact the PRS Administrator: Marianna Betro (firstname.lastname@example.org) and a user account will be created for you so that you can register your trial.
What are the requirements for record updates?
- Clinicaltrials.gov has specific deadlines for record updates (see details here).
- Within 30 days of a change: recruitment status of an individual site, overall recruitment status, completion date
- Every 12 months: any other changes or updates to the record (e.g., protocol amendment)
What are the changes in the U.S. HHS’s and NIH’s rules for Clinical Trials Results Information Submission to clinicaltrials.gov?
- The changes clarify and expand the regulatory requirements and procedures for submitting registration and summary results information of clinical trials on ClinicalTrials.gov, in accordance with FDAAA801. For example, it outlines which trials must be submitted, when they must be submitted, and whether compliance has been achieved.
- Under FDAAA 801, reporting results is not required for a clinical trial that is not an Applicable Clinical Trial.
- According to FDAAA 801, Applicable Clinical Trials (ACTs) are interventional studies of drug, biological and device products that are regulated by the FDA and involves a US site or products manufactured in the US. The final rule applies to ACTs except phase 1 trials of FDA-regulated investigational new drug and biological products, or small feasibility studies of device products. For full definitions, see checklist.
- Effective on January 18, 2017
- Any ACTs that have their primary completion date on or after January 18, 2017 must submit summary results as specified in the rule (i.e., within 12 months).
- Primary completion date = the date of final data collection for the primary outcome measures.
- Responsible parties were expected to be in compliance as of April 18, 2017.
- Note: NIH applies the final rule to all NIH funded interventional trials (whether partial or fully funded, phase 1, feasibility studies, behavioural interventions, etc).
- There may be consequences for non-compliance to the responsible party (which can include hefty fines and suspension of grant funding) which is often a sponsoring institution such as Unity Health (see here).
How detailed are the results required by clinicaltrials.gov and what is time commitment required to update the clinicaltrials.gov registry with a summary report of the results?
- Summary results are submitted in structured tabular forms and require the following information:
- Participant Flow
- Baseline Characteristics (demographics, study-specific measures)
- Outcome Measures and Statistical Analyses: If your trial did not collect all of pre-specified Primary and Secondary Outcome Measures that were initially included in the registration, describe why data could not be summarized to include in the data table (e.g., specify zero (“0”) for the Number of Participants Analyzed in each Arm/Group, leave the data fields blank, and provide an explanation in the Analysis Population Description for why zero participants were analyzed.)
- Adverse Events: If Adverse Events were not assessed/collected, “0’s” can be included for Numbers of Participants Affected and Numbers of Participants at Risk and explain in the Additional Description field that adverse events were not collected.
- For clinicaltrials.gov, adding a link to a publication on PubMed does not fulfill their requirements of summary results reporting.
- Even for Non-Applicable Trials, complete clinical trial results information must be submitted as per the above.
- It is difficult to estimate the time it will take to report the results of a study on clinicaltrials.gov because it varies according to the size/complexity of the trial and how readily available and organized the results are. For a small single site trial, summary results reporting will take 30 minutes to 2 hours.
- Each registry has different rules for summary results reporting (e.g., clinicaltrials.gov requires more comprehensive summary than other registries).
- Tables must be completed by an individual who is familiar with the study design and data analysis (e.g., PI, coordinator).
Will the ICMJE consider clinical trial results posted at ClinicalTrials.gov in compliance with FDAAA 801 to be prior publication?
- The ICMJE does not consider results data posted in the tabular format required by ClinicalTrials.gov to be prior publication (See more information).
For any questions regarding clinicaltrials.gov and the Final Rule, contact the U.S. National Library of Medicine (NLM) Customer Support: