FDA Drug Watch Site Guidelines

As reported in today's Wall Street Journal ("FDA Issues Guidelines For 'Drug Watch' Site, Details on Oversight Board") , the FDA issued a Gudiance (i.e., draft guidelines) last Friday on a "Drug Watch" web site for "Emerging Drug Safety Information" (see "Guidance: FDA’s 'Drug Watch' for Emerging Drug Safety Information" and FAQs).

As the FDA says, "Sometimes after a drug is approved, rare but serious side effects emerge as the drug is more widely used or is prescribed for off-label uses." Vioxx is a case in point (see, for example, Cox-2's Die Hard: With a Vengeance). The proposed web site "is intended to identify drugs for which FDA is actively evaluating early safety signals."

There are a few notable aspects of this proposal that I think deserve commentary.

"Our goal with the Drug Watch," says FDA "is to share emerging safety information before we have fully determined its significance or taken final regulatory action so that patients and healthcare professionals will have the most current information concerning the potential risks and benefits of a marketed drug product upon which to make individual treatment choices."

While it is laudable that the FDA intends to make this kind of information available on its web site, the public may not be aware that a drug has been added to the list unless they go the web site. This may or may not happen.

Rather than relying on a “build it and they will come” strategy, I think that the FDA should follow a more pro-active strategy as it has with the traditional MedWatch program, which notifies doctors about drug safety issues. That program requires pharmaceutical companies to send "dear doctor" letters to all its physician clients. It also enlists professional organizations and web sites focused on docs to notify their members and visitors about Medwatch notices.

Perhaps the FDA should solicit consumer-focused and patient advocacy organizations to join a Drug Watch program through which they are given advance notice that a drug is being added to the list. These groups can then notify their members.

No "Stinking" FOIA Required
"Most of the information that will be posted on our Web site is information that is now made available to the public (after proper redaction of confidential commercial and personal privacy information) in response to Freedom of Information Act (FOIA) requests. Because of the importance of this information to healthcare professionals and patients, we have decided to take steps to make such emerging information available without waiting for a FOIA request..."

Getting information from some government agencies under the Freedom of Information Act (FOIA) has sometimes been a difficult and long process. "[I]n practice, the Freedom of Information Act has not always lived up to the ideals of that Act," according the Findings section of the OPEN Government Act of 2005. It is commendable, therefore, that the FDA intends to post information to the Drug Watch site that, until now, was only available under a FOIA request:

I suspect that this will make some pharmaceutical companies nervous.

Off-label Risks Too!
The FDA says that it will include emerging safety information that may relate to "new risks, new information on known risks, or risks associated with off-label uses."

As you know, a physician can prescribe a drug for any condition, not just the condition for which it was approved by the FDA. This is termed "off-label" use. Drug companies generally are not permitted to promote off-label uses to physicians. However, off-label use may account for a significant fraction of a drug's total prescriptions. See "Guidelines for Off-label Communications" for more information. Therefore, including information about off-label adverse side effects could be very critical information for many people taking drugs for "unapproved" conditions.

How will FDA decide which drugs will be included on the Drug Watch?
This is the million dollar question. The decision will be left up the Drug Safety Oversight Board, which the agency recently created, to decide when drugs are to be added to the list. I can't comment on that until I see how it works in practice. It is worrisome that the Board has the appearance of the fox guarding the hen house as it were.

What About Removal?
Deciding when drugs should be removed from the list is also very important. The Oversight Board will be responsible for that decision as well according to the following guidelines:

1. FDA has determined that, despite the initial signals, there is no new safety concern. I got no beef with that.

2. When its labeling has been revised to address the safety concerns or when FDA has taken other steps to adequately communicate information to healthcare professionals and patients.

Once a drug is listed on the site, I think the entire history should be archived so that people can follow the decision-making process. Perhaps doctors read the black box and adhere to its warnings -- perhaps some do not. But if patients as well as physicians are expected to weigh the benefits vs risks, then there needs to be a forum through which the risk information is continuously available. Patients will seldom see the black box on the package insert.

To Make it Work, Re-Purpose Homeland Security's Color Code System!
During the phase in which a drug is listed on the Drug Watch site and the FDA is doing further investigation, I propose that the drug be placed in a "high alert" zone that is assigned a special color such as red. This would be a good way to re-purpose The Homeland Security Advisory System color scale!

While in this "high alert" zone, DTC ads for the drug should be prohibited. Pfizer voluntarily did this with Celebrex, for example, when asked by the FDA. The drug could still be marketed to physicians who presumably would be getting the latest information about side effects through the Medwatch program.

Perhaps, as I proposed before (see "How the FDA Can Fix DTC"), drug companies would be required to perform more post launch surveillance studies to help evaluate the safety of drugs listed in the "high alert" zone of the Drug Watch site. The restriction on DTC can be provisional upon completion of those studies.

When the evaluation is complete, the drug is either proved to be safe or is relabeled so that risk is addressed, the DTC restriction should be lifted and the drug should be removed from "high risk" zone and placed at a lower alert level. If it proved safe, it could drop down to the green "safe zone" with its history still available. If it gets a black box warning, it may only drop down to one of the other colored zones (orange or yellow) indicating intermediate risk.

Not only would this be a good way to help consumers evaluate risk, it would prevent DTC from unduly influencing the prescribing of drugs under investigation.