We know you’re restless for more information about Form 3674, that beguiling new requirement that the FDA is imposing upon those sponsoring clinical trials.

We were itching to know more ourselves. We rang the FDA. Unfortunately, after the phone call, we can’t say we know much more than before the phone call.

Jarilyn Dupont is director of regulatory policy in the FDA’s office of policy. Her name is printed on the draft guidance as the go-to person for questions. She seemed reluctant to make policy during a media interview or say anything to impact ongoing discussions between the FDA and sponsors. She mostly referred us to the published guidance, which was released in April, four months after filling out the form became a federal requirement under an emergency clearance.

Some Facts

Here’s what we know, from Dupont and the guidance:

Full name of the form, currently in draft version: Form 3674, OMB Control No. 0910-0616.

The purpose of the form? To make sure those conducting trials are registering those trials with ClinicalTrials.gov, the trials database established by the National Institutes of Health (NIH) and the FDA. Clinicaltrials.gov was raised to a new level of prominence in 2005—not by government, of course, but by perhaps a dozen elite medical journal editors, who required that trials be listed in the database as a prerequisite for publication. Here’s some of that history.

Now the government is trying to raise the bar a bit more. Organizations sponsoring trials must now include expanded information on their trials and information regarding the results of their trials. Form 3674 is how sponsors tell the agency they’ve complied with the regulations about clinicaltrials.gov.

Most of the time, we speculate, completing the form will be a routine, ordinary undertaking. But in high-profile instances where every sponsor action is scrutinized under a microscope (or by lawyers for plaintiffs), the presence (or lack thereof) of your company’s Form 3674 in FDA files could be a problem. A gotcha.

Rush Order

Has all this been a problem for sponsors since it kicked in on December 26 of last year? Yes. “There is a lot of confusion about this provision,” said Dupont. “Right now, we’re working with sponsors to ensure that they’re in compliance.”

The origin of the form can be traced to the 2007 renewal of the federal user fee legislation and can be found here in the Federal Register.

Rarely Alone

Form 3674—a one-pager—is not usually submitted on its own, but with certain human drug, biological product, and device applications and submissions to the FDA, says the guidance.

Looking for more specifics? OK, a completed 3674 must be turned in along with any application under sections 505, 515, 520(m), 351, or 510(k) of the Federal Food, Drug, and Cosmetic Act (FFDCA).

But wait. What about the many other submissions that the industry makes to FDA under the drug, device and biologics provisions of the FFDCA? Do those need to have a form 3674 stapled to them?

Maybe. Maybe not. We asked. And the recent guidance was intended to clear that up. Here are its lists of all the submissions that do not require the new form. We hope this helps…

Investigational applications/submissions:  
• Chemistry and manufacturing amendments to investigational new drug applications (INDs)
• Non-clinical pharmacology/toxicology amendments to INDs
• IND safety reports
• Single patient INDs
• Meeting requests
• Investigational device exemption applications (IDEs)

Marketing and post-marketing applications/submissions:
• Chemistry and manufacturing amendments and supplements to biologics license applications (BLAs) and new drug applications (NDAs) non-clinical pharmacology/toxicology amendments and supplements to BLAs and NDAs
• Humanitarian device exemptions (HDEs) and premarket approval application (PMA) 30 day notices
• ANDA amendments and supplements that contain no in-vivo bioequivalence information
• ANDA, BLA, and NDA promotional materials
• BLA and NDA safety reports
• ANDA, BLA, NDA, HDE, and PMA mandatory and voluntary adverse event or medical device reports
• Meeting requests
• 510(k)s that contain no clinical data

So if your document appears on one of the lists above, you don’t have to submit the form. Or ... maybe you do.

To quote the guidance itself, “We recognize that there may be times that the types of submissions discussed above do, in fact, contain information that refers to, relates to, or includes information on an applicable clinical trial that the registry and results databases are intended to capture. In those cases, you should consider whether a certification is appropriate and contact us if you need additional guidance.”

And what about categories of submissions that aren’t on the lists? “As for any other categories not listed in the draft guidance, our current thinking is that certifications are required to be submitted,” Dupont said. Our conclusion: when in doubt, submit the form.

Tracking and Penalties

Other questions we had for Dupont:  How many of the forms have come in so far? Answer: the FDA won’t record the number, since the forms come in with many different types of applications, she said. She directed us to this part of the statute to show how many forms the FDA estimated would be submitted.

What are the penalties associated with not submitting the form? Answer: The entire statute has consequences and enforcement provisions.

And what about timing? Why was the form rolled out as an emergency? When might it be written into law? Dupont said the form had emergency clearance in December because there was a deadline in the statute. In effect, that gave the FDA six months to get permanent clearance from the Office of Management and Budget for it in June, 2008. Will this happen? That answer is not under the jurisdiction of the FDA, needless to say.

by Suz Redfearn