Author Affiliations: Department of Clinical Pharmacy, School of Pharmacy, University of California, San Francisco.
In 2006, the FDA unveiled the first major revision of the prescription drug label in more than 25 years.1 This format, the Physicians Labeling Rule (PLR), was intended to make the drug label easier to read and understand by reorganizing and prioritizing drug information that had become overwhelmingly detailed, complex, and difficult to interpret. In this issue of the Archives, Duke and colleagues2 describe the first quantitative analysis of listed ADEs in the drug label. Extracting more than 530 000 ADEs from 5602 drug labels indexed on the DailyMed Web site, the investigators observed that the median number of unique ADEs had steadily increased from 43 events per label for drugs approved in the 1960s to 63 events per label for drugs approved within the past decade. Almost 600 drugs listed more than 150 ADEs, and 84 listed more than 300. In addition, drugs that conformed to the PLR were documented to have even more ADEs than older drug labels. Although the authors did not address the possibility of bias associated with inclusion of multiple labels for the same drug (eg, methotrexate has 10 labels indexed in DailyMed and amiodarone has more than 20 labels), they have provided us with a glimpse of the overwhelming numbers of ADEs that health care providers must sift through to make informed decisions toward the safe, effective use of a drug for an individual patient.
What risks should be included in the product label? How should the information be presented? While it is important to disclose risk information, overwarning without appropriate context is not helpful. Prescribers ignore vague, difficult-to-interpret warnings, even for risks that have been deemed serious.3 In addition, dizzying lists of all known and theoretical ADEs, regardless of severity, frequency, or causality may discourage prescribers and patients from using a valuable drug. As proof, risk communications have been shown to reduce prescribing of drugs, often with poor health outcomes.4,5
The FDA guidance document on the presentation of information in the “Adverse Reactions” section of the drug label offers a framework for selecting, characterizing and organizing adverse event information.6 The document suggests that ADEs that occur at the same rate as placebo, should generally not be included. Vague terms such as “common,” “rare,” “infrequent,” or “frequent” should be avoided unless linked to specific frequencies. An example of a specified frequency for “common” ADEs would be those that occurred in at least 10% of treated patients and at a rate at least twice that of placebo. Furthermore, ADEs should be reported in a hierarchical manner, with those that occurred with higher frequency first, followed by those that caused therapy discontinuation and those that occurred with lower frequency but were serious (eg, fatal, life threatening, or caused or prolonged hospitalization). In all cases, only those ADEs for which there is plausible causality should be included.
Since these guidances are not legally binding, it is not known to what extent drug labels follow these recommendations. A consistent approach to the selection and risk characterization of ADEs in the drug label is needed, particularly with the documented proliferation of ADEs that now reside in the drug label. At the minimum, drug labels should present ADE information in a standardized format using common terminology and definitions so that health care providers can systematically process and manage the deluge of clinical data. The recommendations set forth by FDA guidance documents provide an excellent starting point.
As with all quality health care improvement initiatives, a validation process for drug labels linked to outcomes—including health care provider comprehension, perception of drug benefits, and risks and usability—as a decision-making tool are needed. The information within the drug label must receive regular, rigorous evaluation for currency and clinical relevance to health care providers of varying background, training, and experiences. While studies exist evaluating modes of effective risk-benefit communications to patients, little has been published regarding communication of drug information to health care providers.7- 9 Responsible oversight on the development and revision of drug labels is necessary to ensure the effective delivery of unbiased, comprehensive, accurate, up-to-date, and user-friendly drug information.
Correspondence: Dr Guglielmo, Department of Clinical Pharmacy, University of California, San Francisco, 521 Parnassus Ave, Ste C152, San Francisco, CA 94143-0622 (firstname.lastname@example.org).
Financial Disclosure: None reported.
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