A systematic review of published studies of US Food and Drug Administration (FDA) warnings and alerts to the general public and health care professionals about unanticipated risks from approved medications over the last 20 years finds that the success of such efforts are “varied and unpredictable.” Although some communication efforts had a strong and immediate effect, many had little or no impact on drug use or health behaviors—and several had unintended consequences—according to the findings published in the January issue of the journal Medical Care.
The FDA uses several tools to inform the public and health care professionals about new evidence related to drug safety, including “Dear Healthcare Provider” letters to subscribers, “public health advisories” and “Safety Alerts” targeting the general public, and “black box warnings” added to a label when a drug’s risks may be particularly severe or affect a large population. While previous studies have examined single alerts, advisories, and label changes, this current review is the first to systematically examine the effect of these risk communications.
The researchers, from the University of Chicago Medical Center, North Shore University HealthSystem, Johns Hopkins Medicine, and Harvard Medical School, found that the most effective notices were those warning the public about potential serious adverse events, but even these varied in their impact. For example, several studies found that an FDA alert about the risk of increased risk of cardiovascular events with the diabetes drug rosiglitazone led to decreased use of the drug by patients and increased use of other, less risky anti-diabetes drugs.
A similar 2010 FDA warning for asthma patients, however, had little effect, the review found. The warning stressed that long-acting beta agonists (LABAs) should not be used without an asthma controller medication, such as inhaled corticosteroids. Rates of controller medication use with LABAs did not significantly increase after the advisory was issued.
Recommendations that specific groups of patients avoid certain medications sometimes decreased use, but also produced unintended consequences, the researchers found. The most notable was a series of advisories about the use of antidepressants among children and adolescents. The widely publicized alerts significantly decreased use of these medications by adults as well as children, however, one study suggested an unexpected increase in suicides among children and adolescents due to increases in untreated depression.
FDA warnings about harmful drug-drug interactions had some impact, although reductions in co-prescribing that occurred often required repeated risk advisories and took months to years. For example, initial messages to reduce the use of cisapride with contraindicated products were first sent in February 1995, but large changes in cisapride co-prescribing were not observed until after the third alert sent in June 1998.
Additionally, the researchers found that FDA recommendations to increase clinical or laboratory monitoring for patients taking certain drugs, produced “no evidence of a large or sustained impact on the FDA recommendations.” For example, recommendations to monitor patients using antipsychotic medications for hyperlipidemia and diabetes showed no changes in glucose testing following the FDA advisory.
Part of the problem, the researchers emphasize, is the challenge of communicating complex risk messages to a large, diverse audience. “The most effective communications were the simplest, those that were specific, where alternatives were available, and where the messaging was reinforced over time,” said Stacie Dusetzina, PhD, one of the researchers from Harvard.
Source: The University of Chicago Medicine