Level of Evidence Associated with FDA Safety Communications with Drug Labeling Changes: 2010-2014

  • Benjamin Hixon
  • Joseph M. Lowrey
  • Lindsay N Hume
  • Katelynn Mayberry
  • Maisha Kelly Freeman Samford University
Keywords: Safety, Drug safety communication, level of evidence


Purpose: Approximately 800,000 safety reports are submitted to the FDA annually, however, only significant issues generate drug safety communications (DSC). The purpose of this study was to determine the type of clinical evidence used to warrant a change in drug labeling for drugs with DSC between January 1, 2010 and December 31, 2014. Methods: Selected data was obtained from the FDA website. The primary endpoint of the study was the frequency of the types of clinical evidence used in FDA communications, as reported through the FDA DSC. Results were evaluated via descriptive statistics, and chi-squared for nominal data. Results: A total of 2521 drug safety labeling changes were identified and 99 (3.9%) of safety communications met the inclusion criteria. The majority of the labeling changes were associated with single agents (83.8%). The three most frequently reported labeling changes were warnings (68.7%), precautions (58.6%), and patient package insert/medication guide (23.2%). Case reports resulted in the greatest number of documented literature types (n = 791), followed by randomized controlled trials (n = 76), and case control/cohort studies (n = 74). Significantly more evidence for DSCs were classified as Level of Evidence B (LOE B, 68.6%), compared to LOE A (17.1%), and LOE C (14.1%) (p = 0.007).
: The majority of drug labeling change initiators was associated with LOE equivalent to B. Practitioners should evaluate data associated with labeling changes to determine how to interpret the information for their patients.

Conflict of Interest

We declare no conflicts of interest or financial interests that the authors or members of their immediate families have in any product or service discussed in the manuscript, including grants (pending or received), employment, gifts, stock holdings or options, honoraria, consultancies, expert testimony, patents and royalties.


Type: Original Research


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Received 2016-12-22
Published 2017-02-14
Practice-Based Research