FDA's criteria for removing a product from the proposed "Drug Watch" website are subjective and will make it difficult, if not impossible, for a drug to be taken off the list, the Pharmaceutical Research & Manufacturers of America said.

The wording in an FDA draft guidance "regarding criteria for removing a product from the...website is highly subjective, and gives little insight into what the criteria will be, and how they will be applied," PhRMA maintained.

The trade association was among numerous stakeholders that filed comments on the draft guidance, "FDA's 'Drug Watch' for Emerging Drug Safety Information," which was released in May.

The agency plans to use the Drug Watch website as a forum for communicating emerging drug safety information to health care professionals and patients before it has fully determined the significance of the safety information or taken final regulatory action (¹ Also see "FDA Rx Safety Website Will Include Drugs With Emerging Off-Label Issues" - Pink Sheet, 9 May, 2005., p. 3).

Decision Tree For Removing Postings

FDA's guidance states that a drug may be removed from the website "when its labeling has been revised to address the safety concerns, when FDA has taken other steps to adequately communicate information to health care professionals and patients, or when FDA has determined that, despite the initial signals, there is no new safety concern."

However, ^FDL-1 PhRMA's comments assert that the "instances where it can be definitively stated that no new safety concern exists will be extremely rare (e.g., proving there is no causal relationship), thereby making removal of a product from the Drug Watch difficult, if not impossible."

FDA should instead develop "a more specific decision tree for removal or deactivation of Drug Watch listings," the trade association suggested.

The agency also should establish criteria for removing a product from Drug Watch if "no new definitive data become available" after a specified period of time, PhRMA said.

The rationale for a product's removal from Drug Watch, and the information upon which that decision is based, should be made available on the site "with the same level of highlighting and publicity that the original posting received," PhRMA said. "This 'exonerating information' should remain on the website for a specified period of time."

Un-Ringing The Bell?

In separate comments, AstraZeneca recommended that a listing on Drug Watch "should appear for no longer than 90 days before it is removed" by either a formalized label change, a health alert or by a "formally documented decision that there is no merit to the information to warrant further formal posting on the website and that no serious health risk exists from the data that was posted."

Industry officials previously have expressed concern that listing a product on Drug Watch will irreparably harm the drug's reputation in the long-term (² Also see "Drug Safety Debate Will Have Long-Term Effect On New Approvals, Troy Says" - Pink Sheet, 13 June, 2005., p. 8).

Similarly, ^FDL-2 AstraZeneca's comments caution that posting "unsubstantiated information" could have a profoundly negative impact on a therapy.

"Removing a drug from Drug Watch or posting clarifying information will not 'un-ring' the bell," the company said. "It is important that FDA use sound and substantial scientific data to trigger a drug's posting" to the site.

Clarifying Posting Criteria

PhRMA's comments lay out several principles for FDA to consider in posting safety information on Drug Watch.

The group suggested that safety-related information posted on the website "should be robust enough to be useful in guiding prescribing and treatment decisions."

Safety information on the site should not create undue alarm among patients or encourage patients to alter or discontinue therapy without first consulting a physician, PhRMA said.

The Drug Watch site should complement labeling, which should "continue to be the primary vehicle for safety-related information to the public."

In addition, FDA should seek timely comment from a sponsor regarding the appropriateness of the information prior to posting on the site, PhRMA said.

FDA's draft guidance provides only that a sponsor be notified shortly before the first time that information about a drug is posted on the website.

Dissemination of "preliminary safety information of unknown significance" creates potential public policy and legal issues, PhRMA warned.

If FDA nevertheless decides to disseminate such information, the agency should better define the threshold for publishing preliminary safety data, revise the disclaimer to better communicate the relevance of the posting and improve the mechanism for revising and removing posted information, the group said.

FDA has proposed the following disclaimer for Drug Watch postings: "This information reflects FDA's preliminary analysis of data concerning this drug. FDA is considering, but has not reached a final conclusion about, this information."

Strengthening Disclaimers

The disclaimers about Drug Watch postings should be strengthened to emphasize the information is still under evaluation by FDA and that no final decision has been made, the ^FDL-3 American Pharmacists Association's comments on the draft guidance state.

"APhA is concerned that visitors to the website may not fully understand that safety risks included on the Drug Watch are potential risks and that no direct relationship has yet been confirmed," the group said.

PhRMA's comments state that the disclaimer should emphasize the health care practitioner's role in evaluating the significance of new safety information for each individual patient.

"A prominent reminder by FDA to 'always consult your physician before modifying or discontinuing treatment with [a medication listed on the Drug Watch website]' will help ensure that patients do not unilaterally stop taking safe and effective medicines based upon information posted on the Drug Watch website," PhRMA said.

The disclaimer should further specify that the information is not considered sufficient to warrant a change in product labeling, PhRMA added. The site also should include an explanation that a posting does not mean the manufacturer is required to take any specific action, the group's comments state.

"The disclaimer should appear prominently on the Drug Watch home page and also on each screen on which product-specific information appears," PhRMA said.

Patient Information Sheets & Liability Exposure

In separate comments, the American Medical Association expressed concern about potential liability ramifications in linking Drug Watch information to Patient Information Sheets.

In the draft guidance, FDA said it is developing Patient Information Sheets to "convey critical facets of a product's approved labeling in lay terms." The sheets will include a section on "emerging safety information" when there is a Drug Watch posting that patients should consider.

AMA cautioned that the sheets could put physicians in the position of having to defend the prescribing of a Drug Watch product. This could "add tensions to the patient-physician relationship or...result in the patient's refusal to take a medically necessary drug," ^FDL-4 AMA's comments state.

The sheets also could trigger liability concerns by "providing plaintiffs' attorneys with documents that imply the drug products have many risks, but few or no benefits," AMA said.

PhRMA expressed similar concern about the potential liability exposure stemming from Drug Watch postings.

"It is almost certain that Drug Watch warnings will be used by plaintiff's attorneys as 'proof' of material safety risks, and that courts will allow the warnings as evidence of causation," PhRMA's comments state.

Rulemaking vs. Guidance

PhRMA asserted that a formal rulemaking process, rather than guidance process, would be a more appropriate regulatory pathway through which FDA could develop a Drug Watch site.

"The purported 'guidance'...constitutes a significant change in existing regulatory procedures and rules for addressing emerging safety information," the group said. "PhRMA believes it is impermissible for the agency to attempt to adopt the Drug Watch program through publication of a guidance document."

FDA "Drug Watch" Listing Removal Criteria Need Greater Clarity - PhRMA

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