title: Impact of United States Food and Drug Administration's boxed warnings on adverse drug reactions reporting rates and risk mitigation for multiple myeloma drugs.
abstract: OBJECTIVE
  To determine the relationship between boxed warnings issuance by the US Food and Drug Administration (FDA) and the proportional reporting rates of the associated adverse drug reactions (ADRs) to the FDA's Adverse Event Reporting System (FAERS) for multiple myeloma (MM) drugs.
  
  
  METHODS
  We compiled a list of all FDA approved MM drugs and identified their associated ADR boxed warnings, through FDA's website and physician desk reference. Drugs that were issued boxed warnings after their market launch were included in the analysis, i.e., melphalan, thalidomide, vincristine, carmustine and doxorubicin. For each drug/ADR boxed warning combination, we retrieved all reported cases from the FAERS and calculated their Empiric Bayes Geometric Means (EBGMs), in pre- and post-boxed warning periods. Chi-square tests were performed to compare serious adverse drug events before and after boxed warnings for all drug/ADR combinations.
  
  
  RESULTS
  A total of 10 drug/ADR boxed warning combinations were identified, of which EBGM signals increased for six combinations after a boxed warning was issued. Reports of serious adverse drug events also increased significantly (p < 0.05).
  
  
  CONCLUSIONS
  Boxed warnings were associated with increased FAERS reporting, indicating increased awareness of ADRs for MM drugs. Proactive pharmacovigilance programs, such as the FDA's Mini-Sentinel Project, may improve timeliness of detection of rare ADRs.
authors.affiliation: University of New Mexico, College of Pharmacy, Albuquerque, NM 87131, USA. vgarg@salud.unm.edu
authors.forename: Vishvas
authors.initials: V
authors.lastname: Garg
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Raisch
authors.forename: June M
authors.initials: JM
authors.lastname: McKoy
authors.forename: Steven M
authors.initials: SM
authors.lastname: Trifilio
authors.forename: Jamiee
authors.initials: J
authors.lastname: Holbrook
authors.forename: Beatrice J
authors.initials: BJ
authors.lastname: Edwards
authors.forename: Steven M
authors.initials: SM
authors.lastname: Belknap
authors.forename: Athena T
authors.initials: AT
authors.lastname: Samaras
authors.forename: Beatrice
authors.initials: B
authors.lastname: Nardone
authors.forename: Dennis P
authors.initials: DP
authors.lastname: West
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D004346:Drug Information Services; D004348:Drug Labeling; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology* / Q000517:prevention & control; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy*; D011358:Product Surveillance, Postmarketing; D012189:Retrospective Studies; D014481:United States / Q000453:epidemiology; D014486:United States Food and Drug Administration
chemical_list: D000970:Antineoplastic Agents