Postmarket Drug Safety: The View From the FDA

Laurie E. Scudder, DNP, NP


May 19, 2017

Editorial Collaboration

Medscape &

Getting the Word Out

Medscape: New information gleaned from postmarket research can be conveyed to clinicians and the public in a variety of ways. Can you describe how the decision about the method for disseminating new information, including timeline, is made?

Dr Dal Pan: The primary way that we let practitioners know about new safety issues is through changes to the product label. The same law that allowed us to require manufacturers to conduct certain studies also gave us the authority to require manufacturers to make changes to their label when we have new safety information. So the label has been and still is the primary tool to convey information that's essential to prescribing the medicine. We may also issue a drug safety communication linked to one of these label changes.

However, sometimes we may issue a drug safety communication before we have the whole story finalized. We may do this to let the public know that there's a signal that we're still evaluating.

We also have a MedWatch listserve that sends information to anyone who signs up, be it an organization or an individual, about label changes we make. Professional societies pick up messages that are relevant to the particular specialty society and disseminate the information via newsletters, conferences, etc.

Along with Aaron Kesselheim and his colleagues at Harvard Medical School, we are studying how these messages are disseminated and where people get information.[1] In 2013, we issued a safety alert about zolpidem-containing medicines to warn about next-day drowsiness and impairment, with a recommendation to change the starting dose. We then followed how these changes were distributed through mass media, such as newspapers and social media, and how prescribing changed.[2] We're interested in better understanding the impact of our actions. Change doesn't happen overnight, but this new information does get integrated into clinical practice over time.

Medscape: What is your advice for clinicians who are using these newly approved agents in their patient care?

Dr Dal Pan: We encourage adverse event reporting of suspected adverse drug reactions. That report doesn't have to be long but ideally is a reasonably detailed summary with sufficient pertinent clinical data to allow an independent health professional reading this report—someone not involved in the patient's care—to make an independent assessment as to what the relationship between the drug and the adverse event might be. So, including pertinent past medical history, reasons for taking the medicine, important diagnostic tests, and the outcome after the event happened is essential.

Beyond that, I would encourage people to read our labels and any updates that we may have on the MedWatch listserve. It's important for health professionals to educate the general public that all medicines—whether prescription or OTC meds, even ones for which we have decades of experience or brand-new ones—have risks and benefits. The critical decision when prescribing medicines is to determine how that risk-benefit profile relates to the patient I'm seeing now. The information on the label is really designed to help clinicians make that determination.

We know that new medicines are going to have new safety issues identified after their approval. Once approved and in use, these medicines are often prescribed for broader populations than the population included in the clinical trials.

Medscape: In light of these new studies, will the FDA change its postmarket safety surveillance programs in an effort to help alleviate concerns about not-yet-recognized safety risks with newly approved agents?

Dr Dal Pan: Let's emphasize that this is not a newly recognized concern.We know that new medicines are going to have new safety issues identified after their approval. Once approved and in use, these medicines are often prescribed for broader populations than the population included in the clinical trials. Patients in the real world are on a lot of different medicines concomitantly and may have a variety of illnesses. Medicines may not be used in a way that the label recommends. The safety of medicines is a combination of the inherent pharmacologic properties of the medicine as well as how the medicine is used in our healthcare system.

We have these systems set up to add postmarket safety information because we know this will happen. We know that medicines will have postmarket safety changes that do, in fact, occur throughout the lifecycle. In a study of safety events that resulted in a label change in 2010,[3] half of the medicines that had a label change that year were on the market for less than 11 years and half were on the market for more than 11 years. This really does occur throughout the product lifecycle, and that's why it's important for the entire system to be attentive.

Medscape: In the JAMA study, it was unclear whether the safety events had occurred with on-label or off-label use.

Dr Dal Pan: Right. Frankly, that is very difficult to understand in all cases—exactly the conditions of use under which the medicine was used. That's a tough thing to get at.

Which is why the postmarket safety surveillance system is not a static system but rather one that is always evolving. We're always looking at new capabilities and methods, as well as our own internal processes—to improve them as well. It is a real, dynamic system, and that is essential.

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