The Final Rule Goes Into Effect

January 19, 2017 Francine Lane

On Wednesday, January 18, 2017, the Final Rule for Clinical Trial Disclosure in the US went into effect.  But what is the Final Rule and what does it mean for study sponsors?

In September 2016, the United States Department of Health and Human Services (HHS) issued 42 CFR Part 11 for Clinical Trials Registration and Results Information Submission, commonly referred to as the “Final Rule”.  This Final Rule was a required update to Title VIII of the Food and Drug Administration Amendments Act (FDAAA) of 2007.  The Final Rule clarifies and completes requirements for registering clinical trials and disclosing clinical trial results.

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Effective Dates

The Final Rule became effective on January 18, 2017, which means that Applicable Clinical Trials (ACT) that start enrolling (study start date) on or after this date need to comply with the protocol registration requirements, and ACTs that complete collection of data for primary outcome measures (primary completion date) on or after January 18, 2017 need to comply with the results section of the Final Rule.  ACTs with a study start date or primary completion date prior to January 18, 2017 are still be subject to FDAAA.

Although the Final Rule went into effect on January 18, sponsors have until April 18, 2017 to comply with the rule.  For protocol registrations, it means that new fields become required and some formerly optional fields also become required on April 18.  Missing data in these fields will trigger a warning validation message until April 18, after which a validation error message will be triggered.  Errors must be resolved before the record can be released.

Because the timeline for disclosing results for ACTs are due one year after the Primary Completion Date, new results data is not required until January 18, 2018.

Application Clinical Trials

The Final Rule attempts to eliminate the ambiguity regarding which studies are applicable under the regulation and which are not.   Studies that are applicable to the Final Rule are defined as Applicable Clinical Trials (ACT) and are identified by the following criteria for drug studies:

  • One or more arms
  • Study Type = Interventional
  • Study Phase is other than Phase 1
  • The clinical trial studies and FDA regulated intervention
  • And at least one of the following applies:
    • At least one site in the US or US territories
    • The drug product (or biologic) under investigation is manufactured in the US or a US territory
    • The trial has an Investigational New Drug (IND) number

For device studies, the following criteria indicates an applicable device trial:

  • One or more arms
  • Study Type = Interventional
  • Primary Purpose of the clinical trial is other than a feasibility study
  • The clinical trial Studies a U.S. FDA-regulated Device Product
  • And at least one of the following applies:
    • At least one site in the US or US territories
    • A device product under investigation manufactured in the US or a US territory
    • The trial has an Investigational Device Exemption (IDE) number

Results Required All ACTs

In the Final Rule, results are required for all ACTs, regardless of approval status.  This means that sponsors are required to provide results for ACT studies for unapproved or uncleared products and indications.   Under FDAAA, results were required for approved products and indications only.

In general, results must be provided one year after the primary completion date, although sponsors do have the option of requesting a delay providing results for up to two additional years for unapproved products or indications.  Sponsors may also request a good cause extension to providing results.  These options were available under FDAAA, but it wasn’t clear if a formal request to delay was required, or if results could simply not be provided until approval.  The Final Rule clarifies that a formal request is required.

Expanded Access

Expanded access, sometime referred to as compassionate use, provides an unapproved medical product outside of a clinical trial.  Providing information on expanded access programs was optional prior to the Final Rule.  Now, sponsors who are also manufacturers of the investigational product are required to provide information about expanded access, and link relevant studies to the expanded access record.

New and Newly Required Data

The Final Rule defined both new data fields and makes previously optional data fields required.  The combination of newly required and new data elements allows an ACT to be identified based on the data profile.

Updates to Registration and Results

Under FDAAA, studies needed to be updated every 12 months, unless there was a change to the overall status of the study, or the study completed, which required an update within 30 days.  The Final Rule increases the number of data elements that trigger an update on a more frequent basis. 

The approval or clearance status of a device must be updated within 15 days of approval or clearance.  Study dates (study start date, primary completion date, study completion date) and the enrollment status when the study completes must be updated within 30 days of a change.  Overall study recruitment status and individual site status (including for sites outside the US) changes must be updated within 30 days.  Once a non-proprietary name is issued, the intervention name must be updated within 30 days.  Availability or changes to expanded access must be updated within 30 days, as well as linking relevant studies to the expanded access record.  If there is a change to the Human Subjects Protection Review Board status or a change to the responsible party, updates are required within 30 days.  Lastly, the verification date must be updated at least every 12 months while the study is ongoing, with a complete review of all submitted data.

Correcting Data

Each record is reviewed by a member of the team prior to publication on the website.  The Final Rule defines that sponsors must address issues raised by the quality review within 15 days for protocol registration data, and within 25 days for results data.  Records that have outstanding issues will be published on the website with a notification that the data does not meet the quality standards.


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