The expanded HHS mandate that clinical trial investigators publish their full results on ClinicalTrials.gov is backed up with strong consequences for non-compliance that will be enforced by the FDA and the National Institutes of Health.

Starting in 2017, HHS will require that all clinical trials — even privately funded, industry-sponsored studies, as well as studies that fail to hit their endpoints — must register and publish their results in the public database in a timely manner.

“I’m expecting a flood of trials to get registered,” said FDA Commissioner Robert Califf.

“I agree with that,” said NIH Director Francis Collins. “I don’t think anyone wants to be on the wall of shame.”

Previous regulations, such as those issued under the FDA Amendments Act of 2007, were very ambiguous in defining which trials needed to report their results. The rule new provides a clear checklist to determine whether a clinical trial falls under the requirements. ClinicalTrials.gov currently hosts over 224,000 registered trials, but only about 10 percent provide full study results.

“This will be a change in business as usual,” said Collins during a conference call with reporters. “This is not a rule that lacks compliance; it does in fact have some teeth.”

The HHS rule does not apply to Phase I clinical trials or small device feasibility studies, but it does cover controlled investigations of products subject to FDA regulation and interventional studies evaluating a device. International studies that have at least one site in the U.S. will also be subject to the rule.

Deadlines for Posting

Researchers will be responsible for registering on ClinicalTrials.gov within 21 days of enrolling their first patient, and must submit recruitment information, site locations and contacts. Trial results must be posted within one year of the trial’s completion, but the rule allows for a possible delay of up to two additional years for trials of unapproved products.

Although not previously required, the results submission now must include outcomes and statistical analyses, detailed adverse event data, and a full copy of the protocol and statistical analysis plan, and requires that all submitted information be updated at least once a year.

The rule, first proposed in 2014, drew more than 900 comments. After consideration, HHS added new provisions previously not required under FDAAA, including requirements for adverse event reporting and the submission of the full study protocol.

Compliance will be enforced by the FDA through its Bioresearch Monitoring program, and coordinated with NIH.

“People have asked why we haven’t done this before — it’s because there’s been a lot of ambiguity — but we’re ready now,” Califf said during the conference call.

Typical enforcement actions will include publicly available warning letters, Califf said — FDAAA requires that the agency send a notice of noncompliance and allow an opportunity to correct the violation. Subsequent penalties include civil fines of up to $10,000 per day, the withholding of grants for federally funded trials, and being publicly identified on ClinicalTrials.gov as non-compliant.

“We would not stop clinical trials in progress — that would be unethical — but we will have the ability to withhold future funding until the problem has been corrected,” said Collins.

The NIH released a separate, complementary policy that would apply to all NIH-funded studies — this would include Phase I and device feasibility studies, as well as behavioral trials and studies into service delivery, which do not include an FDA-regulated product — further broadening the scope of trials subject to the reporting requirements, beyond the HHS rule.

The rule goes into effect Jan. 18, 2017, and requires compliance within 90 days, by April 18, 2017.

The NIH plans to connect its databases of grantee information and ClinicalTrials.gov to monitor compliance with reporting. “Our goal is to have all NIH-funded trials in ClinicalTrials. gov,” said Collins.

Additionally, Collins encouraged the use of an NIH-developed clinical trial protocol template, in coordination with FDA and international guidances, to help standardize the submission of trial details, and said that he expects the use of a single institutional review board in multi-site studies.

The NIH is also planning to require good clinical practice training for investigators and NIH staff responsible for overseeing clinical trials, and develop a standardized electronic system to ensure accountability

Let’s face it. You’re under more pressure now than ever to conduct more complex and larger trials — and to do them faster. Data Integrity in Clinical Trials: Ensuring Valid Results details the challenges of maintaining data integrity in clinical trials and offers solutions for closing gaps that can lead to tainted results.