Case reports and post-marketing surveillance

The Food and Drug Administration has launched an online training seminar, "FDA MedWatch and Patient Safety," about the role of the MedWatch program in monitoring drug, device, blood, and other biologic product safety in the US.

It's a fantastic and informative course, about an hour of video presentation, covering the role that the program plays in monitoring safety after drugs, devices, etc, are approved by the FDA - commonly called "post-marketing surveillance."

Programs like this realize that, while clinical trials are designed to establish general safety and efficacy of the products regulated by the FDA, they do not have adequate size to detect all possible side effects; the MedWatch program is particularly interested in serious adverse events associated with these products, i.e. those causing significant morbidity and mortality to individuals taking the drug. This type of program also is intended to catch issues with:
- how drugs are prescribed (what patients and physicians "do" with the drugs outside of the controlled setting of a clinical trial, such as problems with how they're dosed, possible interactions with other medications, etc)
- how devices or other products are used in the "real world"
- quality of products (issues regarding how the devices, drugs, products are produced and distributed to patients, e.g. faulty devices, manufacturing/handling errors leading to problems with the end product, etc)

The stated objectives of the MedWatch program:

- To educate both healthcare providers and their patients about the importance
of reporting serious adverse events IN to FDA, and to facilitate that reporting

- then…once those reports have been received and evaluated by FDA, to
take the new safety information that results from analysis of these reports and
disseminate it OUT from FDA and back to clinicians and their patients, in a
timely fashion for use at the point of care.

The FDA pulls these reports together, analyzes and investigates them, and determines an appropriate course of action for dealing with an issue that truly exists. Any interventions or changes are often accompanied by educational strategies aimed at the provider and the patient.

The MedWatch site notes:

Changes to the label, also known as the prescribing information or package insert, are the most commonly used strategy. These range from boxed warnings placed at the top of the prescribing information, to additional statements in contraindications, precautions or adverse reactions sections about new interactions, monitoring recommendations or dosage adjustments. Certain drugs are required to have medication guides - a 'patient-friendly' instruction sheet that is provided to the patient by the pharmacist each time a prescription is dispensed.

How does this tie in to this month's case study?

The foundation of the MedWatch program is voluntary and mandatory reporting of adverse events (errors, product problems, side effects) potentially associated with FDA-regulated products -- in essence, providers and patients sharing case reports of problems potentially associated with the products. Investigators at the FDA use principles of epidemiology to wade through all of the case reports, identify clusters or common issues, investigate those issues, and figure out which problems are "real" and begin figuring out what to do with them -- all based on case reports from providers and patients.

The system is not without its flaws, and potential reform at the FDA is currently the subject of much attention and debate in the US consumer and healthcare communities. An editorial in JAMA highlights some of the main critiques or weaknesses of the current system, and proposes potential solutions for addressing these issues:

Editorial: Fontanarosa PB, Rennie D, DeAngelis CD. Postmarketing surveillance--lack of vigilance, lack of trust. JAMA. 2004 Dec 1;292(21):2647-50. (PubMed abstract with link to free full-text)

Additional information:
- A transcript of the presentation is available here.
- There are a number of articles looking at how MedWatch data is used, available via a quick PubMed search.
- Additional discussion of the FDA's post-marketing surveillance strategies is available on their Center for Drug Evaluation and Research (CDER) site.