Adverse events rise, but meaning debated

A new study shows the number of drug therapy-related deaths and injuries reported to the Food and Drug Administration (FDA) nearly tripled between 1998 and 2005,1 but exactly what those numbers mean is the subject of some dispute. Do they mean that these years of increased attention to preventing drug errors were for naught?

Not necessarily, say the experts, but the number of errors may mean that risk managers should focus on exactly what kind of errors were revealed in the study — particularly, new biotechnology products.

A researcher at Wake Forest University School of Medicine in Winston-Salem, NC, and colleagues reviewed serious and fatal drug events reported in that eight-year period to the FDA by consumers, health professionals, and drug manufacturers. They found that serious adverse drug events increased 2.6-fold, from about 35,000 to nearly 89,000, and adverse drug-related deaths increased 2.7-fold, from about 5,500 to more than 15,000.1

The FDA receives these reports of serious adverse drug events through its Adverse Event Reporting System (MedWatch). This system has been in operation under the same database system since 1998, with consistent regulatory requirements for drug manufacturers.

A few drugs account for many errors

The study also reported serious events increased four times faster than the total number of outpatient prescriptions during that period, and that is an important point, says Curt Furberg, MD, PhD, professor of public health sciences at Wake Forest University School of Medicine and a co-author of the report. "It shows current efforts to ensure the safety of drugs are not adequate, and that physicians and patients are unaware of these risks," he says.

Furberg has previously called for far-reaching changes in drug safety regulation, including expanded authority for the FDA, higher priority for drug safety, and new systems to monitor drugs once they are approved by the FDA. For risk managers, a key finding from the study is that many of the adverse drug events involved the same medications, says Thomas J. Moore, AB, lead author of the study and a senior scientist for drug safety and policy at the Institute for Safe Medication Practices (ISMP) in Huntingdon Valley, PA.

"The study found that a relatively small number of drugs accounted for the most reported serious adverse drug events," he says. "This represents an opportunity to focus efforts at reducing and preventing adverse events by focusing on those common elements."

More errors or just more reporting?

The study is intriguing, says Deborah A. Wible, PharmD, chief pharmacy officer at Beth Israel Medical Center and St. Luke's — Roosevelt Hospital Center in New York City. However, Wible draws a somewhat different conclusion than the authors. While she does not doubt that the number of adverse drug events is high, she says the study's time period coincided with a major push in health care to more fully and accurately report drug errors. Thus, she suspects that the results are skewed by increased reporting.

Furberg says the researchers took into account several factors that might influence their findings. "We saw no evidence that doctors and patients had become more active in reporting events in some across-the-board fashion," Furberg says. "We also tried to eliminate 'noise' in the reporting system, by excluding reports from more than 14 days after a drug was withdrawn. In addition, we excluded events that were not serious and foreign reports to focus on U.S. risks."

Wible says risk managers should not be unduly alarmed by the apparently distressing numbers in the report. But she says there still are meaningful data in the report. "One of the things this does is remind us that when these new drugs come out, they were tested in very controlled conditions on limited populations, and then we start using them on thousands and millions of patients," she says. "Especially with immuno-modulators and new biotech drugs, this is often when we find out a lot more about the effect of these drugs. It's a useful point to keep in mind that we still need to encourage very close monitoring of individual patients even after the clinical trials."

Fragmentation blamed for errors

There is an increased number of errors, says Bruce Lambert, PhD, professor of pharmacy administration at the University of Illinois at Chicago College of Pharmacy and an expert on adverse drug events and patient safety. With an increase in prescriptions, an increased number of errors would be expected, he says. But the way the number of errors is outpacing the increased drug use is troubling, he says.

"So why is that happening? One reason is that we have more fragmentation of the system, making it harder to manage people's drug therapy," Lambert says. "Patients are seeing many different doctors, being treated at different hospitals, and getting their drugs from different pharmacies."

Another explanation is a trend of patients living longer with more illnesses and more serious illnesses, he says. Patients also receive more outpatient care instead of hospitalization, which means there is less opportunity for close oversight of drug interactions and other potential problems.

"In addition, we have more powerful medications being taken," he says. "For many of these new drugs, we need to take blood samples and monitor the effects frequently, but because of fragmentation, sometimes that doesn't get done."


1. Moore TJ, Cohen MR, Furberg CD. Serious adverse drug events reported to the food and drug administration, 1998-2005. Arch Intern Med 2007; 167:1,752-1,759.