Full article reprinted from "The Gray Sheet" - January 26, 2009
Find out how final guidance published Jan. 21 provides answers for device companies still confused about how and when they must certify to FDA that they have registered their clinical trials on ClinicalTrials.gov.
FDA explains that a completed certification form should be included with the submission of a PMA; PMA panel track supplement; Humanitarian Device Exemption application; or 510(k) that "refers to, or relates to, or includes" information on a clinical trial.
Relatively few 510(k) submissions will be affected. As FDA notes, the large majority of 510(k)s do not include clinical trial data, and therefore will not need to include a certification. The necessary certification form, FDA Form 3674, is available at 1www.fda.gov/opacom/morechoices/fdaforms.
The certification requirement is part of a new program, created by the 2007 FDA Amendments Act, requiring device companies to register their clinical trials with the National Institutes of Health's Clinical Trials Data Bank. NIH posts the registration information - including the study's purpose, endpoints and eligibility criteria- on the ClinicalTrials.gov Web site after the related device is approved or cleared for marketing by FDA.
The statute says pre-market submissions must be accompanied by a certification that the registration requirements were met. Until now, there has been uncertainty about which of the many types of pre-market submissions fall under the certification requirement.
FDA's first crack at the issue, in an April 17, 2008, draft guidance, added to the confusion by stating which types of submissions did not need accompanying certification, rather than which did (2"The Gray Sheet" June 23, 2008, p. 3). The final guidance corrects that problem, affirmatively listing the submission types covered.
The guidance also clarifies that FDA does not expect companies to submit certifications with regular PMA supplements (as opposed to panel track supplements) and 510(k)s not involving clinical trial information.
FDA states that requiring certifications with these two categories of device submissions "would serve little or no purpose."
Soft Touch On Enforcement
Theresa Toigo, director of FDA's Office of Special Health Issues, said industry is "generally complying" with the certification requirements. When a certification form is missing, the CDRH reviewer "contacts the submitter and requests that the form be submitted," she said.
In related enforcement matters, CDRH Office of Compliance official Michael Marcarelli said the center is leaning toward a "reminder-type" approach rather than an "enforcement-minded" approach to companies that violate the Clinical Trials Data Bank provisions, for instance, by submitting promotional or false and misleading information along with their registrations or results.
"Right now we're developing policy on that," Marcarelli, who directs the compliance office's division of bioresearch monitoring, said in a December interview.
"I think the idea here is to send reminder letters if companies are not doing what they're supposed to be doing, and not to take major enforcement actions against them. That's sort of where we're heading, but I don't know how exactly that's all going to shape up."
An internal FDA group is working to develop a "consistent and standardized" approach to enforcement, including for cases where violative companies do not respond to gentle reminders, Marcarelli said.
NIH: "Things Are Going Well"
NIH has been receiving about 30 device trial registrations a week, according to Jerry Sheehan, assistant director for policy development at NIH's National Library of Medicine. That is almost double the weekly average of 18 prior to passage of the FDA Amendments Act, which made device trial registration mandatory for the first time.
Altogether, about 2,100 device clinical trials were registered between September 2007, when the FDA Amendments Act passed, and Jan. 15, 2009. Of those, 175 remain hidden from public view pending pre-market approval or clearance of the related device.
Since passage of the act, about a dozen trials have been "unhidden" and posted on the public Web site, Sheehan said. Many of the other device trials on the Web site are public because they are of a type that does not fall under the act, Sheehan noted.
Results Reporting Under Way
Provisions of the law that went into effect last fall also require device companies to report the results of their clinical trials to NIH for posting on the ClinicalTrials.gov site. Results must be reported within a year of trial completion (3"The Gray Sheet" Sept. 29, 2008, p. 8).
As of Jan. 15, results of four device trials had been posted on the public Web site, according to Sheehan.
"The numbers of registrations and results reports submitted for device trials suggest that things are going well," Sheehan told "The Gray Sheet." He said data submitters "are learning that reporting of results - whether for trials of drugs, devices or other interventions - requires the engagement of people who are familiar with the details of the trial."
He explained, "Submitted results tables must be logical, informative and understandable to people unfamiliar with the study."
To help data providers avoid common errors in their submissions, NIH has posted "helpful hints" and a training webinar at 4http://prsinfo.clinicaltrials.gov/fdaaa.html
Sheehan added that there have been some continued questions about the specific types of device trials subject to the registration and results reporting requirements, and that NIH recently posted additional information on that topic on the ClinicalTrials.gov site.
The next major development for device companies will be the issuance of a regulation explaining how companies should go about reporting information on serious or frequent adverse events from clinical studies, and how those adverse events should be presented on the ClinicalTrials.gov site.
The FDA Amendments Act requires NIH to publish that regulation by March 27, 2009. If it fails to do so, default provisions contained in the act will go into effect on Sept. 27 of this year.
Neither Sheehan nor FDA's Toigo would comment on the status of the rulemaking.
- Mary Houghton
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