On Aug, 25, when the FDA announced two new cases of progressive multifocal leukoencephalopathy (PML) in European patients receiving natalizumab (Tysabri) monotherapy for multiple sclerosis for more than one year, the message went out instantaneously via-email to the desktops of thousands of health professionals and patients who had signed up for the FDA MedWatch alerts.
The spotlight on patient safety has intensified over the past eight years since the release of the 2000 Institute of Medicine report, “To Err is Human” and unsurprisingly, the size of the FDA MedWatch e-mail list has grown steadily from 4,000 to over 100,000 individuals. Similarly, each month, nearly one million people visit the MedWatch Web site, www.fda.gov/medwatch, a 75 percent increase in Web visits from one year ago.
THE BENEFITS OF MEDWATCH
Ellis R. Diamond, MD, co-chair of the AAN Patient Safety Subcommittee, believes the e-list notification is one of the great advantages of practicing medicine during this age of technologic innovation and information availability. “The alerts help keep neurologists informed about potential risk issues of medications and other products that we prescribe, as well as those medications and products that have been prescribed to our patients by other practitioners,” he explained.
As chief patient safety officer at the University of Pennsylvania Health System, Daniel M. Feinberg, MD, said the alerts help him keep up to date. “Many of our patients are on 10 or more medications and interactions are common and not often appreciated,” he observed. As co-chair of the AAN Patient Safety Subcommittee, he encourages AAN members to sign up for the e-list and review the categories for appropriateness. Subscribers may set their preferences to receive immediate, daily, weekly, or monthly updates and select from a variety of alerts including biologics, drugs, devices, and research.
AAN.com Science Editor John Henson, MD, and his editorial board members have subscribed to the listserv for the past year. Links in the e-list forward the editor to the FDA MedWatch Web site to review the postings and select those of interest to neurologists. Since September 2007, 22 alerts have been posted on AAN.com after being screened. “In many cases the relevance is obvious, as with the risk of suicide in patients on antiepileptic drugs (AEDs),” he said. “In other cases, the relevance may be less obvious to the broader neurologic community, as with a recent alert about cardiotoxicity from mitoxantrone.”
Because the alerts are widely publicized, neurologists are fielding more drug safety questions from patients than ever before. “While potentially very useful, a program such as FDA MedWatch involves certain risks,” said Sheryl Haut, MD, a member of the AAN.com Science Editorial Board and director of adult epilepsy at the Montefiore Medical Center. “The news [in a January report about AEDs and increased risk for suicide] was widely released to the medical and general public, but it was only part of a bigger picture,” she said. She noted that the alert indicated that all AEDs potentially increased the risk of suicide. But considering that patients with epilepsy require treatment with AEDs, “it created a difficult situation for both physicians and patients,” she said.
On the positive side, Dr. Haut pointed out that this process can provide opportunities for greater communication with patients. “Bringing up AEDs and suicide risk with patients may prompt an important discussion of the overall risk of suicide and other psychiatric disorders in epilepsy, and allow neurologists to suggest strategies to prevent these risks.”
WILL ALERTS LOSE THEIR VALUE?
With 166 safety alerts released in 2007, at a frequency of about three a week, some physicians are wondering whether their impact has lost some of its value. “The FDA has become more aggressive about releasing alerts for potential problems of low frequency or where only preliminary data are available,” Dr. Henson acknowledged.
“For many alerts it is simply sufficient to be aware of the potential problem and to be prepared for questions from patients,” he advised. Dr. Henson believes that the higher frequency also serves to keep MedWatch communications in neurologists' minds. “They help to raise awareness of the incomplete nature of our knowledge of side effects from agents and devices, and remind the practitioner that the identification of rare but important side effects often requires analysis of population based studies,” he explained.
UCSF cerebrovascular specialist S. Andrew Josephson, MD, also a member of the AAN.com editorial board, is concerned that the frequency of warnings may run the risk of ‘alert fatigue.’ “I think it makes us all somewhat wary of seeing them each week and I am more careful to try to examine the primary literature, when available, that drives the alert,” he said.
Although he recognizes that the warnings are a good way to notify physicians of new data or recommendations that would directly affect their practice, he believes that the more these alerts are used, the less likely an important alert will reach as many doctors as it may have in the past.
“The alerts will be maximally valuable if they only contain priority information, of interest to large numbers of clinicians and patients,” agreed Dr. Haut.
But Dr. Diamond is unconcerned about the volume of alerts. He has refined his interests on the Web site, allowing for him to gain a degree of control without being left out of the information loop. He also uses folders within his inbox to categorize alerts of active concern, possible concern, and limited concern. “It only takes a few instances of becoming aware of major risk factors that are brewing within your own patient population to become alert once again. I find the alerts informative, useful and applicable to everyday responsibilities,” he said.
Gerald J. Dal Pan: What Neurologists Should Get from MedWatch
Neurologist Gerald J. Dal Pan, MD, became the director of the Office of Surveillance and Epidemiology (known then as the Office of Drug Safety) in the FDA Center for Drug Evaluation and Research (CDER) in November 2005. Prior to that, he was the director of the Division of Surveillance, Research, and Communication Support in CDER's Office of Drug Safety, a position he held since December 2003.
Dr. Pan is board certified in internal medicine and neurology. He joined the FDA in July 2000 as a medical officer in the Division of Anesthetic, Critical Care, and Addiction Drug Products.
Dr. Pan agreed to answer some questions for Neurology Today about the FDA Medwatch program.
WHY SHOULD NEUROLOGISTS USE FDA MEDWATCH?
MedWatch was designed to give practitioners timely, new safety information about the drugs and medical devices they prescribe or use every day. The FDA recognizes that in many different work settings, neurologists may wish to direct these e-mail alerts to one point of contact, for example, an office manager or clinical nurse, who can triage these messages, routing those of clinical importance to those in the group who need to know.
MedWatch encourages practitioners, patients, and consumers to report suspected adverse drug reactions or other problems with medical products to FDA. These direct reports remain the primary source of early warnings, or signals of previously unexpected adverse events, that allows FDA to initiate the evaluation and investigations that lead to new knowledge about the safety of these drug products and devices.
HOW CAN THE INFORMATION ON NATALIZUMAB HELP US IN THE CARE OF MS PATIENTS?
FDA has a good bit on information on natalizumab on the FDA Web site. The FDA page for natalizumab contains updated safety information, details of the risk management plan for the therapy, the product's professional label, and other useful information. This information can be useful in deciding if natalizumab is appropriate for an individual patient, for counseling the patients, and for monitoring the patient.
THE RELEASE ABOUT SUICIDE RISK IN ANTIEPILEPTIC DRUGS WORRIED MANY NEUROLOGISTS. HOW SHOULD WE COUNSEL OUR PATIENTS?
Neurologists should continue to weigh the potential benefits and risks of antiepileptic drugs in each patient, and make prescribing decisions based on that analysis. Neurologists can use this information to counsel patients.
WHAT ABOUT ALERT FATIGUE? HOW DO YOU BALANCE TOO MUCH INFORMATION WITH TOO LITTLE?
We are concerned about “alert fatigue,” as practitioners have many sources of information facing them each day. We are actively exploring new methods — both new technologies and process changes — to better target our alerts to audiences of interest and deliver them at the point of care so they can be considered during therapeutic and diagnostic decisions. We welcome input from practitioners on the best way to communicate information in a useful and timely way.
ANYTHING ELSE THAT NEUROLOGISTS SHOULD KNOW?
Knowledge of a drug's effects, including adverse effects, proceeds throughout its entire lifecycle. It is important that practitioners keep up to date with new drug safety information.
Resources: FDA MedWatch Alerts
If the medical and neurological communities aren't yet fully attuned to the potential of the FDA MedWatch service, the plaintiffs' bar most certainly is. There are multiple law firm Web sites listing the various MedWatch alerts, and inviting queries from patients who think they may have been injured from these drugs. If a neurologist does decide to use a drug about which there has been a MedWatch alert, it would make good sense to address the issue directly in the chart, explaining clearly the rationale behind the decision.
To sign up for FDA MedWatch Alerts: www.fda.gov/medwatch/elist.htm
To access the FDA MedWatch Home Page: www.fda.gov/medwatch/index.html
To submit a report to FDA MedWatch: www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm