FDA's Oversight Board Sees Growing Range of Drug Safety Issues

Pauline Anderson

August 26, 2010

August 26, 2010 ( UPDATED August 30, 2010 ) — In the 5 years since the Food and Drug Administration's (FDA's) Drug Safety Oversight Board (DSB) was formed, the topics discussed by its members have evolved from ones pertaining to a single drug or drug class to those broaching much broader drug safety issues.

Recent topics of discussions have included the deaths among children with attention deficit hyperactivity disorder (ADHD) taking stimulants, the abuse and misuse of opioids, fire risks linked to alcohol-based skin preparations, and the potential cancer risk of CT radiation.

Staff from the Center for Drug Evaluation and Research (CDER) updated the media on August 25 in Silver Spring, Maryland, about the role and make-up of the DSB.

The DSB was formed in 2005 and mandated into law in 2007 in response to public calls for closer scrutiny of drug safety. This followed the removal from the market in the late 1990s and early 2000s of several high-profile drugs, including Hismanal (Janssen), Propulsid (Janssen), and Vioxx (Merck).

"During this time of turbulent drug withdrawal, the FDA faced both internal and external challenges," said Cheryl Grandinetti, PharmD, CDER science policy analyst.

"The FDA at that time had no formal mechanism to resolve differences in opinion or decide when and how to communicate and alert the public about a drug safety issue under evaluation," Dr. Grandinetti explained. "Externally, the FDA was often criticized for acting too slowly when presented with adverse event data and drug safety signals."

Board Make-Up

The board is made up of 28 members, including 20 from the FDA (18 from CDER plus 1 each from the Center for Biologics Evaluation and Research and the Center for Devices. and Radiological Health, 3 from the National Institutes of Health, and 1 each from the Centers for Disease Control and Prevention, Veterans Health Administration, Agency for Healthcare Research and Quality, Department of Defense, and Indian Health Service).

The board also invites guest experts from other federal agencies and from outside institutions to provide advice on drug safety issues. For example, last November, the director of the cardiac catheterization lab at the Mayo Clinic joined a board meeting to give a perspective from cardiologists at his institution on the potential interaction between clopidogrel and proton pump inhibitors.

The board is not a federal advisory committee but, rather, an internal management council that does not fall under the Federal Advisory Committee Act. It provides advice to the CDER director on handling and communicating important and often emerging drug safety issues and provides a forum for discussion about how to address these issues.

Deaths Among Children With ADHD

Among issues recently tackled by the board was the sudden and unexplained death among children with ADHD taking stimulants. "The controversy involved whether the drugs caused an increased cardiovascular risk in children without known cardiac disease," said Martin Kaufman, DPM, CDER science policy analyst. "They were already labeled for children with cardiac disease. There was also controversy about the need for cardiac testing before a child was started on a stimulant medication for ADHD."

The board ultimately recommended that the available information was insufficient to make definitive conclusions and that the issue should continue to be monitored. It also recommended that CDER issue a drug safety communication to coincide with publication of a study that found an association between stimulant use and sudden unexplained death.

Consideration of a change in the drug label to include the potential risk for cardiovascular adverse events in children with ADHD who are otherwise healthy should be pending follow-up information from another study partly funded by the FDA, said Steven Osborne, MD, executive director of CDER.

Alcohol-Based Skin Preps

Another recent topic of discussion was the safe use of alcohol-based skin antiseptics in the operating room. Fires in the operating room possibly linked to these preparations occur at an estimated annual rate of 50 to 200 per year.

In that case, the board recommended changing the label to contain a stronger message, talking to hospitals that had fires, and studying how alterations in the design, materials, and specifications might reduce risks for fires.

Anyone from the CDER can submit a topic to the board, which meets monthly. The meetings are open to CDER staff but the public is not permitted to attend. Public summaries are posted on the FDA Web site.

These summaries have expanded over the years. "Prior to April 2009, you may have seen a bullet or two, a sentence or two, and once in a while a paragraph," but now they are much longer and include more information, said Dr. Osborne.

However, the board's recommendations to the CDER director are not included in these summaries, partly so that board members "can make an important decision without undue pressure from parties that we are trying to serve," said Dr. Osborne. He pointed out that there is already significant input from federal partners, academia, clinics, and hospitals.

"Spirited Opinions"

Although for the most part the FDA has "moved away from internal struggles or dissention and is in general working better together," Dr. Osborne acknowledged that some of the DSB meetings still invite "spirited opinions." Rather than detail this discussion in the public summaries, it is best for the public make its own conclusions, Dr. Osborne said. "I think you can assume that if it's a hot topic in the outside environment, there are a variety of opinions in the drug safety board meeting."

Adding information about the nature of the meeting to the public summaries could be counterproductive, added Dr. Osborne. "Rather than being transparent, it could just be opening up a larger can of worms; we're trying to do our best in offering information but not trying to complicate our own process here."

A CDER spokesperson provided clarification to Medscape Medical News, saying that minutes for all DSB meetings are available under the Freedom of Information Act, after redaction of confidential product information. And, as mentioned earlier, public summaries of the meetings are available on the FDA Web site.

Gregory D. Busse, PhD, from the Office of Communications at CDER, stressed the importance of ensuring the information in these summaries is accurate and correct and presented in the proper context.

Not all safety issues lead to formal discussion by the board. For example, said Dr. Osborne, the board is aware that the diabetes drug rosiglitazone (Avandia; GlaxoSmithKline) is in the news, but the board has not been asked to play a role in formal discussions on safety issues pertaining to this drug.

Drug Safety Communications

As for the FDA's Drug Safety Communications, Dr. Busse outlined when such a communication might be required. For example, a communication might be released if the safety issue involves a drug that is widely or frequently used, if an adverse event is serious or life threatening, or if there are new contraindications for a drug that providers need to know to prescribe it appropriately.

According to Dr. Busse, the board has "outreach" initiatives to organizations that should learn the information contained in a particular communications. Staff also use professional societies to "facilitate the movement of the information to their constituents," he said.

Dr. Busse and colleagues are in the process of developing a program to determine whether these communications are reaching the intended audience and are having an effect on clinical practice.

"Ultimately, our goal is to have a kind of bidirectional relationship with the patient healthcare community where we not only issue a drug safety communication, but we're also listening to the feedback and are tailoring those communications so that they get the information they're most interested in and we can provide them with the information that's relevant to them," Dr. Busse said.

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