Study: Rx Warnings Ignored

Serious warnings on high-risk medications are inconsistently heeded by doctors in ambulatory care settings, according to a study that a Harvard researcher published Friday.

Anita Wagner, an assistant professor in the Department of Ambulatory Care and Prevention at Harvard Medical School, led the study, which examined patients who had received one of 19 drugs with Black Box Warnings (BBW) to determine how doctors comply with prescription warnings.

BBW’s are the strongest warning labels, given to high-risk medications by the FDA. They are used to indicate drugs that are associated with what Wagner described as “special problems, particularly those that may lead to death or serious injury.” The warnings themselves are printed in a black frame in a package insert for the drugs. According to Wagner, these warnings are the FDA’s primary means of communicating risks to prescribers.

During the study, which was published online in the Nov. 18 issue of Pharmacoepidemiology and Drug Safety, the researchers collected information about 917,000 ambulatory-care patients from across the country over a two-and-a-half-year period.

They found that 42 percent of these patients received high-risk medications with BBW’s. The team of researchers looked at 219,000 patients who had received one of these drugs. The warnings associated with the medications were classified into three groups: drugs requiring laboratory monitoring, drugs that were unsafe to take simultaneously with other medications, and drugs that were unsafe to take while pregnant.

The study showed that there was significant variability in the consistency with which these three types of warnings were heeded by doctors. The highest adherence was linked to those drugs that indicated they were unsafe to take while pregnant—only 0.3 percent of the prescriptions may have been given to pregnant women.

For the group of drugs that were unsafe to take with other medications, Wagner found that nine percent were prescribed on the same day as drugs deemed unsafe to take simultaneously.

But the study’s most significant finding was the high level of non-adherence to the warnings on drugs that required laboratory monitoring upon dispensation—49.6 percent of these prescriptions were not accompanied by lab tests or monitoring, even though the BBW explicitly states this requirement.

Wagner noted that a significant number of these cases of non-adherence were linked to drugs that required liver-function tests. She suggested that the non-adherence may have to do with questions regarding the need for these tests.

“There is quite a bit of debate as to whether liver-function tests prevent liver injury from drugs, and physicians may just have that lack of evidence in their minds,” she said.

The study sheds new light on the difficulties in communicating drug warnings to doctors and patients.

“One of the main things that I hope it does is alert us to the fact that we don’t know how to communicate dangers to millions of prescribers and patients,” Wagner said.

Wagner also found that the warnings that were most specific were also most effective.

Wagner emphasized that the drug prescription system needs a new strategy to help improve the communication of risks to prescribers and patients. She suggested an automated electronic notification system that would alert physicians to specific drug warnings through their computers at the point of prescribing.

“If the information is applicable to the patient they’re with that moment, the likelihood that they would pay attention to it is much larger,” Wagner said.