Final Rule Results – What You Need to Know

Francine Lane

January 17, 2018

JANUARY 17, 2018

On January 18, 2018, results for applicable clinical trials (ACTs) with a primary completion date on or after January 2017 start becoming due under 42 CFR Part 11 for Clinical Trials Registration and Results Information Submission, commonly referred to as the “Final Rule.”

While most data required under the Final Rule aligns with previous requirements for disclosing clinical trial results on, there are some key differences that you need to know.

Increased Scope of Results Disclosure

Results are now required for all ACTs that are required to be registered, regardless of approval status. The Final Rule expands the disclosure requirements to include results for unapproved products and unapproved indications for studies that were started on or after January 17, 2017 or have a primary completion date on or after January 17, 2017.

Certification of Delay is Required to Delay Results Submissions

The option to submit a Certification of Delay to postpone results when an initial product or new use/indication approval is pending is not new. However, under the FDAAA 801 Requirements, it was not clear whether or not this Certification of Delay was optional or mandatory. The Final Rule clarifies this, and states that if you want to delay your results disclosure for a pending approval, you must submit a Certification of Delay before your results would otherwise be due.

Certifications of Delay Expire

Under the Final Rule, a Certification of Delay will expire two years after it is submitted. Results are still due within 30 days of initial product or indication approval when you have requested a delay, but if the product or use hasn’t been approved within two years of submitting the Certification of Delay, results must be disclosed.

New and Newly Required Results Data Fields

The Final Rule introduced an all-cause mortality table to Adverse Events, which must be completed when disclosing results. In addition, formerly optional data have become required. The NIH has published a list of Changes from Current Practice Described in the Final Rule. All data fields included in this document are required for Final Rule, but it conveniently shows which data fields became mandatory with the Final Rule.

One key data change that warrants some extra attention is that statistical analyses are now required in three instances as described in § 11.48 (a) (3) (v) (A) of the Final Rule:

1. Pre-specified in the protocol and/or statistical analysis plan and was performed on the outcome measure data,

2. Made public by the sponsor or responsible party prior to the date on which clinical trial results information is submitted for the primary outcome measures(s) studied in the clinical trial to which the statistical analysis applies, or

3. Conducted on a primary outcome measure in response to a request made by FDA prior to the date on which clinical trial results information is submitted for the primary outcome measure(s) studied in the clinical trial to which the statistical analysis applies.

Inclusion of Protocol and Statistical Analysis Plan

The Protocol and the Statistical Analysis Plan, if it isn’t included in the Protocol, must be submitted to at the time results are submitted in the PDF/A format. All amendments that are approved by a Human Subjects Review Board must be submitted, therefore multiple versions may be needed to meet this requirement. These documents can be redacted as described in § 11.48 (a) (5).

Data Corrections Due Within 25 Days

Data submitted to undergoes a quality assessment. Comments resulting from this assessment will be categorized as Major or Advisory. Major comments on results data must be addressed within 25-days. Advisory comments are not required to be addressed.

Four Tips to Prepare for Final Rule Results

1. Make sure your study teams, and especially statisticians are aware of the new data requirements. They may need to prepare additional data to for disclosure or be required to address comments in a short timeframe.

2. Communicate with the study teams and publication groups about disclosure. In some cases, presenting exciting new findings at a congress or in a publication may increase the scope of required disclosure.

3. Understand the product and indication/use approval status for each study and be prepared to submit a Certification for Delay within a year of primary completion date if you don’t plan to disclose results at that time.

4. Remember to leave enough time to prepare and redact, if applicable, the protocol and the statistical analysis for submission.

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About the author

As Vice President of Global Transparency for TrialScope, Francine is responsible for helping customers meet and exceed current disclosure expectations globally, giving them the tools they need to meet all the requirements in this evolving industry. She also serves as chair of the Drug Information Association (DIA) Clinical Trial Disclosure Community.