FDA On Trial Registries: Manufacturers Should Steer Clear Of Claims

Manufacturers should be cautious about drawing explicit conclusions about the outcome of clinical trials posted on public registries, FDA Division of Drug Marketing, Advertising & Communications Director Tom Abrams told a Pharma Audioconference Oct. 26.

If a study focuses on an off-label use or a potential head-to-head comparison to another therapy, interpretive statements included in study reports could be construed as promotional claims subject to FDA regulations, Abrams suggested.

"If you post the data - just the data - without drawing conclusions of safety and efficacy... you'd most likely be fine," Abrams said.

On the other hand, concerns could arise when "you make conclusions and you put conclusions up," Abrams said.

Abrams also suggested the agency has fewer concerns about data posted on "a corporate website" devoted to registries than it does about "using sales representatives and things like that."

New York Attorney General Eliot Spitzer recently negotiated settlements with GlaxoSmithKline and Forest that will require the companies to publish summaries of clinical trials on the Internet (¹ (Also see "Forest Settles With Spitzer; Trial Registry Will Focus On Phase III-IV" - Pink Sheet, 13 Sep, 2004.), p. 8).

A group of leading medical journals is requiring registration of clinical studies in a public registry at the time of study initiation as a prerequisite for publication.

The International Committee of Medical Journal Editors cited ClinicalTrials.gov as the only database currently meeting its requirements. Legislation is pending in Congress that would require posting of study results on the ClinicalTrials.gov site (² , p. 5).

The push for full disclosure of clinical trial results was driven in part by the argument that negative study results of an off-label use typically do not receive the same exposure as positive studies.

In that respect, the push for registries is viewed as a way to discourage inappropriate off-label use of medicines.

However, the registries could also become a vehicle for publication of studies supporting an off-label use or comparative claim that would not survive FDA scrutiny.

"We would caution companies from using this as a promotional tool to promote off label," Abrams said.

"Posting of clinical trial data can be done well and done in a non-promotional way," Abrams said. "If certain steps are taken, there's not a concern about going into a promotional realm."

The FDA ad division will examine the "content and context" of a posting to determine whether it is promotional.

On the content side, FDA will ask: "Are there promotional claims within the text of the posting? Are you making promotional claims by drawing conclusions from the data?" Abrams said.

"Are you posting studies that were positive to your drug or all the studies, both negative and positive? Are you dismissing or minimizing negative trial results?"

As for context, FDA will ask: "How are you using this? Are you putting this information in sales aids?"

"It's best to ensure that this is completely separated from the sales promotion," Abrams said.

"Keep it out of the sales representatives' hands. By involving the sales representatives, I think that would lead you down the wrong road."

The clinical trial registries are arising at a time when FDA's ability to regulate dissemination of study results by sales representatives is uncertain in the wake of the WLF ruling in 2000 (see ³ (Also see "Off-Label Promotion Remains Vulnerable To Prosecution, DoJ Says" - Pink Sheet, 1 Nov, 2004.)).

Abrams noted that FDA can and does review reprint campaigns. "We can use the dissemination of reprints as evidence of intended use," he noted.

"Historically, I think it's important to note, before WLF, before all this, we did not take many actions against reprints. We do review reprints. We review many avenues of promotion," Abrams said.