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Posted on 11.18.05
Warning Labels on High-Risk Drugs Not Always Heeded by Doctors
By Julie McKeel
A study of nearly 930,000 ambulatory care patients found that 42% of the patients received prescriptions for drugs with Black Box Warnings (BBW), the Food and Drug Administration¹s strongest label for high-risk drugs. In addition, clinicians were inconsistent in complying with the BBW recommendations, which suggests that better methods are needed for ensuring the safe use of medications that carry serious risks.
[BBWs are warnings printed in a black frame in the package insert of some drugs. They are intended to warn doctors about the serious risks that may be associated with certain drugs. BBWs must appear on all promotional materials and include a description of the drug's risks. The warning can also list specific precautions for the drug's use.]
Researchers from the Department of Ambulatory Care and Prevention (DACP) of Harvard Medical School and Harvard Pilgrim Health Care, Richard Platt (chairman of DACP and principal investigator of the Agency for Healthcare Research and Qualityfunded Prescribing Safety Study), and colleagues across the country conducted a retrospective study over 30 months to find out how many ambulatory care patients were given drugs with BBWs and to measure physician compliance with these warnings.
In the categories studied, doctors' noncompliance with BBWs ranged from 0.3% to 49.6%. These results are reported in the Nov. 18, 2005 online issue of Pharmacoepidemiology and Drug Safety .
"In ambulatory care settings, approximately 1.4 billion prescriptions are written per year," said Anita Wagner, Harvard Medical School assistant professor at DACP, in the press release. "Until now, there has been no information about how frequently doctors prescribe many BBW drugs, nor whether prescribing is consistent with the warnings. This study tells us that these drugs are prescribed often and that in some categories, prescribing is inconsistent with the warnings."
To analyze physicians' adherence to the recommended warnings, Wagner and colleagues examined approximately 217,000 of the patients enrolled in the study. These patients had received at least one of 19 BBW drugs. The selected drugs required laboratory monitoring when a patient began taking the medication or for the duration of the prescription; were unsafe to take with other specific medications; or were unsafe to take while pregnant.
From this group, 49.6% of all prescriptions that should have been accompanied by a lab test once the patient began taking the drug were not. Recommendations for pregnancy tests were most frequently ignored (for example, when women of childbearing age were given prescriptions for acitretin, which treats severe psoriasis).
When laboratory monitoring while taking a medication was recommended, monitoring was lacking in 12.8% of the treatments during which the warning recommended a test
Nine percent of prescriptions considered unsafe to take together were written on the same day. Each of these cases involved prescriptions for methotrexate with non-steroidal anti-inflammatory drugs (NSAIDS) or ketorolac with other NSAIDS (11 and 7.6 percent, respectively).
However, adherence to recommendations was good for labels warning that a medication was unsafe to take while pregnant. Women of childbearing age received almost 79,000 prescriptions for BBW drugs that should be avoided during pregnancy. Only 95, or 0.3 percent, may have occurred during pregnancy.
"We need several things to improve the effectiveness of the warnings: to be clear about the magnitude of risk that justifies a BBW and the evidence that underlies a recommendation, to communicate warnings clearly to both clinicians and patients, and to create systems that support doctors and patients in following the recommendations," Wagner said in the press release. "We believe our data shed light on adherence to BBW recommendations and provide a preliminary basis for recommendations to improve communication about the risks of medicines."
For instance, concise and focused wording of a warning might be more effective. Automated and patient-specific alerts to BBW drugs or recommendations initiated as soon as the clinician prescribes the drug may be more effective than BBWs in package inserts.
This automated alert system would require complete, consistent, and current lists of BBW medicines and the clinical circumstances associated with the risk of disease and death. Since BBWs are the FDA's primary way to protect the public from potentially dangerous effects of medicines, t he authors of this study recommend that the FDA establish and maintain the comprehensive alert list.
Patients do receive drugs that carry the potential for serious risk. Since it will not be possible to avoid certain drug-associated risks, it will be important to develop effective methods to use BBWs and other methods to minimize risks.
"This will require new information about risks, about the way drugs are used in everyday practice, about effective methods of influencing clinicians' prescribing, and about ensuring that patients understand how to use their drug as safely as possible," Wagner said in the press release.
This work was supported by a grant from the Agency for Healthcare Research and Quality (AHRQ) to the HMO Research Network Center for Education and Research on Therapeutics (CERTs). The mission of the CERTs is to conduct research and provide education that advances the optimal use of drugs, medical devices and biological products.