The compliance date for the Final Rule implementing the clinical trial reporting requirements of Section 801 of the Food and Drug Administration Amendments Act (FDAAA), also known as FDAAA 801, arrived on April 18, 2017. The Final Rule implementing the statute came into effect almost ten years after the statutory requirements of FDAAA 801 were enacted. The Final Rule on Clinical Trial Registration and Results Information Submission was issued by the National Institutes of Health (NIH) and covers requirements for data that must be submitted to ClinicalTrials.gov. The data reporting requirements apply to sponsors, or, under certain circumstances described in the Final Rule, principal investigators, of certain clinical trials and postmarket surveillance required by FDA for drugs, biologics, and medical devices. This Bulletin provides a brief overview of what is considered an applicable clinical trial under the regulations, what data need to be submitted, and who is the responsible party. Sponsors with currently active clinical trials should ensure that they are in compliance with the Final Rule and evaluate existing clinical trials and new clinical trials going forward under the criteria described in the Final Rule.
What is an “applicable clinical trial”?
The term “applicable clinical trial” is defined in FDAAA 801 and generally includes controlled clinical trials, other than phase 1 investigations, of drugs and biologics, as well as certain device trials. The following would be considered controlled clinical trials:
- Placebo concurrent control trial
- Dose-comparison control trial
- No intervention concurrent control trial
- Active intervention concurrent control
The Final Rule provides additional information on how to identify which studies are covered. Pediatric postmarket surveillance of medical devices is also considered an applicable clinical trial. Applicable clinical trials include interventional studies with sites in the United States conducted under an IND (investigational new drug) or IDE (investigational device exemption). If a clinical trial is initiated and takes place entirely in a foreign country, but then later adds a site in the United States, it would then become an applicable clinical trial and would need to be registered.
When must an applicable clinical trial be registered?
Applicable clinical trials must be registered at ClinicalTrials.gov within 21 days of enrolling the first human subject in the United States. Under FDAAA 801, registration is required for applicable clinical trials that were initiated after September 27, 2007.
What registration information should be included?
Registration must include the following data elements:
- Descriptive information (title, summary, study design, etc.)
- Recruitment information (eligibility criteria, recruitment status, etc.)
- Location and contact information (name of the sponsor, facility information, etc.)
- Administrative data
What trial data need to be submitted?
The responsible party (the sponsor or designated principal investigator) must submit both the full clinical trial protocol and the statistical analysis plan for any applicable clinical trial with a primary completion date on or after January 18, 2017. For applicable clinical trials with a primary completion date before January 18, 2017, results must be submitted if the product is approved as of the primary completion date. If the primary completion date was before January 17, 2018, but the product was not approved, then results need not be submitted.
The responsible party also must submit a summary of the number and frequency of adverse events the clinical trial participants experienced. Results information, including the clinical trial protocol and statistical analysis plan, must be submitted no later than one year after the primary completion date. However, submission may be delayed for up to two more years if the responsible party certifies the product is still under development, or that the sponsor intends to seek approval for a new use of its approved product. The certification is submitted through the Protocol Registration and Results System.
Who is the responsible party?
The sponsor of the clinical trial is considered the responsible party for submitting the required information, but in some cases the responsibility can be designated to a principal investigator who meets specified qualifications. The principal investigator of the clinical trial can be designated the responsible party if she:
- Has access to and control over the data from the trial
- Has the right to publish the results of the trial
- Is able to meet all of FDAAA’s requirements for submitting clinical trial information
If the designated principal investigator is unable to submit the required information, then the obligation reverts back to the sponsor.
What are the consequences for non-compliance?
Potential consequences for not complying with the Final Rule include civil and criminal actions, civil monetary penalties, and grant funding actions. NIH will also post notices flagging non-compliance with the regulations on ClinicalTrials.gov. The notices will include the nature of the non-compliance and any penalties imposed.
- We work with many companies who receive at least partial funding through the NIH. The NIH has stated in the NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information, published in tandem with the Final Rule, that the reporting requirements apply to all NIH-funded clinical trials, regardless of whether they would be considered applicable clinical trials under this Rule.
- We know that expanded access policies are still on many companies’ “to-do” list, but note that the provision of an investigational new drug on an expanded access basis, whether through a single-patient IND or a protocol that provides expanded access to a larger group, such as a treatment IND is not considered an applicable clinical trial under the Final Rule. Information on whether or not expanded access to the investigational product is available must be separately submitted. Additionally, under the new requirements in the 21st Century Cures Act, manufacturers must include a hyperlink to the clinical trial record in their publicly-posted expanded access policies.
- Trial sponsors outside of the United States should be aware that if they open a trial site in the US, the entire clinical investigation will be considered the applicable device or drug clinical trial, not just the US-based site. This means that the clinical trial registration must include information applicable to the trial as a whole.