FDA risk communication system yielded inconsistent results

Dusetzina SB. Med Care. 2011;00: 000–000.

When the FDA disseminates risk communications about drugs or drug utilization, the results may vary greatly, according to recent findings.

Researchers from several sites in the United States reviewed literature pertaining to the FDA’s drug-risk communication system. Forty-nine of 1,432 records screened were eligible for analysis. Eligible studies were those published from January 1990 to November 2010 that empirically evaluated the effect of an FDA risk communication and contained terms associated with drug utilization, the FDA and advisories or warnings. Other data extracted included the drug or drugs analyzed, relevant communications from the FDA, the source of the data, the method of analysis and the outcome measures assessed.

G. Caleb Alexander, MD, associate professor of medicine at the University of Chicago, told Infectious Disease News that there were four types of risk communications evaluated: “warnings about serious adverse events, recommendations against use in specific patient populations, cautions regarding drug-drug interactions and calls for increased laboratory or clinical monitoring.”

Alexander said the most effective communications were the ones that were “simple, specific, provided alternative therapies or drugs, and were reinforced over time.” He cited an FDA alert linked to the diabetes drug rosiglitazone that demonstrated many of these characteristics.

Other risk communications were not so effective, according to Alexander. “Drivers of drug use exist within a sea of information,” he said. “Predicting whether a risk communication will be effective is difficult, as our results indicate.”

The findings covered 16 medicines or therapeutic classes. Communications for antidepressants comprised one-third of the studies. There was variety in the data sources and statistical analysis methods used, but most of the studies used medical or pharmacy claims. Patient–provider communication, decision-making or risk perceptions were evaluated in fewer studies. “The data sources we were using were so varied that it was difficult to perform quantitative analyses,” Alexander said.

FDA advisories recommending increased clinical or laboratory monitoring were linked to decreased drug use, according to the results. However, these advisories were linked to moderate, transient increases in monitoring.

Communications aimed at specific subpopulations often demonstrated effect on other subpopulations. The largest decreases in drug utilization were observed with drug-specific warnings, but it was also observed that the magnitude of substitution within therapeutic classes demonstrated variation across clinical contexts.

Alexander said an effective risk communication need not necessarily lead to decreased use of the drug in question.

“The ultimate goal is to cause more informed decision-making,” he said. “An advisory or communication may be effective, even though no changes in use of the drug occur.”

The researchers concluded that the effect of risk communication is “varied and unpredictable.” They said the use of risk communication to ensure safe use of medications is complex and requires consistent evaluation.

“Identifying factors that are associated with rapid and sustained responses to risk communications will be important for informing future risk communication efforts,” they wrote.

In this article, the authors seek to assert a causal relationship between FDA communications regarding drug adverse effects and risks with subsequent patterns of prescribing behavior and drug usage. They find a variable, but disappointing small relationship. Unfortunately, the underlying assumptions of such an analysis are faulty and therefore the findings are unreliable. Far more variables determine patterns of drug prescribing behaviors and their changes than merely FDA bulletins and notices. Chief amongst these confounders are the impact of publicity and media attention afforded each issue. These gain patient awareness, which in turn may change physician prescribing behavior. Collateral commentary in professional journals confirming or minimizing FDA concerns also modulate responses to FDA alerts. Finally, the subject matter often determines the degree of concern attached to the FDA communication. For example, comments regarding cancer risks with drugs are taken more seriously than concerns regarding relatively rare but non-fatal adverse effects. There are no controls for any of these confounders in this analysis and therefore the conclusions must be interpreted in light of these limitations.

– Alan J. Garber MD PhD

Professor, departments of medicine, molecular and cellular biology, biochemistry and molecular biology

Baylor College of Medicine

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