title: Warnings without guidance: patient responses to an FDA warning about ezetimibe.
abstract: BACKGROUND
  In January 2008, the Food and Drug Administration (FDA) communicated concerns about the efficacy of ezetimibe, but did not provide clear clinical guidance, and substantial media attention ensued. We investigated the proportion of patients who discontinued therapy and switched to a clinically appropriate alternative after the FDA communication.
  
  
  METHODS
  Using claims data from a national pharmacy benefits manager, we created a rolling cohort of new users of ezetimibe between January 2006 and August 2008 and created a supply diary for each patient in the year after cohort entry. A patient was identified as nonpersistent if a gap of 90 days was seen in the diary. Using segmented linear regression, we compared rates of nonpersistence before and after the FDA communication and assessed patient-level characteristics associated with discontinuation. Among nonpersistent patients, we determined whether a patient made a clinically appropriate switch in the subsequent 90 days by adding a new cholesterol-lowering medication or by increasing the dose of an existing one. We used a weighted t test to compare the rates of appropriate switching before and after the communication.
  
  
  RESULTS
  Among 867,027 new ezetimibe users, 407,006 (46.9%) were nonpersistent in the first year. After the FDA communication, the monthly level of ezetimibe nonpersistence increased by 5.7 percentage points (P<0.0001). Younger patients, those who lived in low-income zip codes, and female patients were less likely to discontinue therapy (P<0.0001 for all). Among nonpersistent patients, rates of clinically appropriate switching increased from 10.8% before to 16.5% after the FDA warning (P = 0.004).
  
  
  CONCLUSIONS
  A substantial increase in ezetimibe nonpersistence rates was seen after an FDA communication regarding its efficacy and following associated media attention, and a small proportion of patients made a clinically appropriate switch after discontinuation. Further consideration is needed to deliver messages that promote appropriate use of chronic therapy rather than simply reduce use.
authors.affiliation: Department of Medicine, Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Harvard Medical School, Boston 02120, USA. wshrank@partners.org
authors.forename: William H
authors.initials: WH
authors.lastname: Shrank
authors.forename: Niteesh K
authors.initials: NK
authors.lastname: Choudhry
authors.forename: Angela
authors.initials: A
authors.lastname: Tong
authors.forename: Jessica
authors.initials: J
authors.lastname: Myers
authors.forename: Michael A
authors.initials: MA
authors.lastname: Fischer
authors.forename: Kellie
authors.initials: K
authors.lastname: Swanton
authors.forename: Julie
authors.initials: J
authors.lastname: Slezak
authors.forename: Troyen A
authors.initials: TA
authors.lastname: Brennan
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Liberman
authors.forename: Susan
authors.initials: S
authors.lastname: Moffit
authors.forename: Jerry
authors.initials: J
authors.lastname: Avorn
authors.forename: Daniel
authors.initials: D
authors.lastname: Carpenter
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001384:Azetidines / Q000008:administration & dosage / Q000009:adverse effects*; D015331:Cohort Studies; D003142:Communication; D003257:Consumer Product Safety; D004363:Drug Utilization; D000069438:Ezetimibe; D005260:Female; D017408:Guidelines as Topic; D006801:Humans; D007345:Insurance Claim Review / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D012723:Sex; D014481:United States; D014486:United States Food and Drug Administration; D055815:Young Adult; D016903:Drug Monitoring
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D000069438:Ezetimibe