FDA's "Drug Watch" website will include safety information on drugs that have emerging safety signals for off-label uses.

"Whether an unapproved (off-label) use of the drug appears to pose a significant risk to patients" is one criterion that will be used to determine which drugs will be posted on Drug Watch, FDA said in a ^FDL-1 draft guidance released May 5.

FDA will also consider posting safety information on the website if "new and emerging safety information could significantly affect prescribing decisions or how patients should be monitored" or if "measures can be taken as a result of providing information that could help prevent or mitigate harm," the guidance states.

The agency plans to use the Drug Watch website to disseminate emerging drug safety information on marketed products to healthcare professionals and patients. It will provide FDA with a forum through which it can communicate emerging drug safety information to the public before the agency has fully determined its significance or taken final regulatory action.

FDA's monitoring of off-label uses and the potential for it to warn against certain unapproved uses through the website could raise concern among those who have sensed an increasing intrusion by the agency in medical practice. FDA maintains that it does not regulate the practice of medicine, but some observers perceive paternalism in the agency's risk management programs (¹ Also see "FDA Public Information Strategy Is “Dangerous” And “Imprecise” – AEI Fellow" - Pink Sheet, 2 May, 2005., p. 11).

The draft guidance warns drug manufacturers against using Drug Watch information in product promotions.

"FDA recognizes that some sponsors may consider drawing promotional comparisons between their products and products that appear on Drug Watch," the guidance states. "In turn, some sponsors whose products appear on the Drug Watch may want to minimize the effects of the information that FDA has made public."

However, FDA believes that the information posted on Drug Watch will typically be insufficient to support marketing claims.

"Neither the fact that a drug appears on the Drug Watch nor the specific information posted about that drug will generally constitute (either separately of collectively) substantial evidence or substantial clinical experience to support a comparative safety or efficacy claim."

"Therefore, comparative claims made in prescription drug promotion based on information on the Drug Watch (e.g., 'Our drug is safer because of the adverse event information posted on the Drug Watch about a competitor's drug'; or , 'Our drug is safer because it is not on the Drug Watch') may be considered false and misleading."

In addition, "representations made to minimize the effect of the emerging risk information on the site may also be considered false or misleading," the guidance states.

During a congressional hearing held the same day the guidance was released, FDA officials discussed whether Merck should have included emerging risk information on Vioxx in its detailing.

Three categories of emerging drug safety information will be posted on FDA's website.

"For some drugs, the web page will contain factual information about newly observed, serious adverse events associated with the use of a drug that have been reported to FDA," the guidance says.

"For other drugs, the web page may contain information about significant emerging risks that FDA believes may be associated with a drug, but that might be avoided by appropriate patient selection, monitoring, or use of concomitant therapy."

"A third category of information might be posted on the Drug Watch when an important risk minimization procedure is put into place by a sponsor in response to emerging information," the guidance states.

A disclaimer will accompany the information posted on Drug Watch emphasizing the preliminary nature of the information.

The disclaimer will indicate that the posted information "reflects FDA's preliminary analysis of data concerning this drug," and that "FDA is considering, but has not reached a final conclusion about, this information," the guidance states.

FDA will continue to convey information about drug risks that are better understood through traditional communication methods.

FDA will remove the safety information as soon as the safety issue is resolved; for example, FDA could revise the product's labeling to include the safety risk or the agency may determine that there is no new safety concern.

According to the guidance, sponsors will be notified that information about a drug will be added to the Drug Watch page "shortly before the first instance in which information about that drug is posted on the web site."

FDA has not indicated whether sponsors will be informed of any subsequent changes to the information on the site. However, the site will include information about the status of the agency's analysis of the safety issue.

The Drug Watch website will be managed by the Drug Safety Oversight Board.

The committee will be composed of 15 voting members, including three members each from the Center for Drug Evaluation & Research's Office of Drug Safety and Office of New Drugs, a CDER Manual of Policies & Procedures states.

CDER will provide five additional members from different center offices. The Center for Biologics Evaluation & Research, the Center for Devices and Radiological Health, a non-FDA HHS agency and a non-HHS healthcare providing agency will also each provide one member.

The CDER deputy director (Douglas Throckmorton) will serve as the non-voting chair of the board. The Office of Medical Policy director (Robert Temple) will also serve as a non-voting member.

The Oversight Board will require a two-thirds majority to make recommendations, the ^FDL-2 MaPP released May 5 states.

The super-majority requirement will help FDA avoid the ambiguity that may result from close votes, as the agency has experienced in recent advisory committee votes on drug safety. FDA decided to withdraw Pfizer's Bextra (valdecoxib) despite an advisory committee recommendation that the COX-2 inhibitor should continue to be marketed (² Also see "Celebrex Should Stay On Market, FDA Panel Says, But Splits On Vioxx, Bextra" - Pink Sheet, 21 February, 2005., p. 3)

Any CDER organizational unit can refer a drug safety issue to the board for assessment by submitting a request to the executive director. The drug safety and new drug offices can also nominate items for board evaluation.

The oversight board will be responsible for adjudicating organizational disputes regarding the management of drug safety issues, the MaPP states. The process for resolving differences of professional opinion is outlined in a previous MaPP.

The board will decide which products to include on Drug Watch and how information will be presented on the site.

Information about Drug Safety Oversight Board meetings will be primarily accessible through Freedom of Information Act requests.

"The Board often will be considering in its deliberations confidential information and options and recommendations that are sensitive and pre-decisional, and normally not disclosed," a question and answer ^FDL-3 document states. "Therefore, the deliberations of the Board will not be routinely disclosed."

Emerging safety information will only be posted on Drug Watch after FDA conducts a "preliminary analysis to determine that the new safety information is sufficiently credible to warrant public dissemination," the guidance states.

The agency will post the information "only when we believe that the data are significant enough to warrant further consideration to determine whether an actual safety problem exists."

FDA has posted drug-specific information for 210 products on a CDER web page, replacing an earlier listing of seven products with safety concerns. The web page is an interim step before the launch of the Drug Watch site.

The previously listed products were the eczema therapies Elidel (Novartis) and Protopic (Fujisawa); Biogen Idec/Elan's multiple sclerosis therapy Tysabri ; the COX-2 inhibitors Vioxx (Merck), Bextra (Pfizer) and Celebrex (Pfizer); and AstraZeneca's cholesterol agent Crestor (³ Also see "CDER Drug Safety Website Model Includes Elidel; Novartis Objects" - Pink Sheet, 25 April, 2005., p. 6).

Of the seven products, only Vioxx is not listed on the new drug-specific site; the COX-2 inhibitor was withdrawn from the market Sept. 30.

FDA Rx Safety Website Will Include Drugs With Emerging Off-Label Issues

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