By Lisa Seachrist

Washington Editor

WASHINGTON — The FDA has moved to relax restrictions on what information drug and device company representatives may present to physicians concerning off-label uses of their products.

The agency released proposed rules in the Federal Register Monday as part of the implementation of the Food and Drug Administration Modernization Act of 1997 (FDAMA). The proposed rules would allow manufacturers of durgs and devices to distribute studies describing unapproved uses that have been published in peer-reviewed scientific and medical journals, as long as the manufacturer agrees to follow up with a submission for FDA approval of the use.

"This is the first time this has been allowed," said Jeff Trewhitt, media spokesman for the Pharmaceutical Research and Manufacturers of America (PhRMA). "Doctors should at least have the information; they should be able to assess it for themselves and decide whether to prescribe drugs off-label in their practice. There is a great deal of balance in the provision."

Once a drug, biologic, or medical device has been cleared for marketing by the FDA, physicians may use the product for any indication they choose. Up until passage of FDAMA, however, manufacturers were barred from distributing information about unapproved uses for their products regardless of the body of clinical evidence supporting such uses.

Rules Would Allow Distribution Of Journal Articles

The agency has stated the prohibition was designed to encourage manufacturers to file supplemental applications for additional uses of their products. While the proposed rules would allow companies to provide reprints of clinical studies to physicians upon agency approval, William Schultz, FDA Deputy Commissioner for Policy, noted that the dissemination of information is tied to the commitment to do the necessary research on new uses.

Under the agency's proposed rules, manufacturers may distribute information in the form of an unabridged reprint or copy of a peer-reviewed scientific or medical journal article, or an unabridged reference publication. The manufacturer must submit the information it wishes to disseminate to the agency 60 days prior to beginning distribution. The agency will then review the material to ensure that it doesn't pose a significant health risk to the public, isn't false or misleading, and discloses that the information is for an unapproved use.

The FDA also will examine whether the information is balanced, scientifically sound, and the product of an adequate clinical study. The manufacturer will be required to include the official product label, disclosure of potential conflicts of interest and a bibliography of other articles relating to the new use.

In addition, the company already must have submitted a supplemental application for the new use; certify it has completed the studies for the application and will file within the next six months; or provide an adequate protocol and certify the application will be submitted within 36 months of the initial distribution. The FDA may exempt a company from filing an application if the necessary studies are either unethical or economically prohibitive.

It is unclear how many companies will be interested in pursuing dissemination of off-label information. Many may not wish to go to the expense of conducting additional clinical trials and filing an application. Nevertheless, the provision allows manufacturers an opportunity they haven't had in the past.

"This is a mechanism for making sure that physicians get the most up-to-date information," Trewhitt said. "Most doctors read the big journals like the Journal of the American Medical Association and the New England Journal of Medicine. But some very important work could appear in journals they don't always keep up to date on."

The FDA is accepting written comment for the next 45 days and expects to implement the rules later this year. *