Did FDA Decisionmaking Affect Anti-Psychotic Drug Prescribing in Children?: A Time-Trend Analysis

PLoS One. 2016 Mar 31;11(3):e0152195. doi: 10.1371/journal.pone.0152195. eCollection 2016.

Abstract

Background: Following Food and Drug Administration (FDA) approval, many drugs are prescribed for non-FDA-approved ("off-label") uses. If substantial evidence supports the efficacy and safety of off-label indications, manufacturers can pursue formal FDA approval through supplemental new drug applications (sNDAs). We evaluated the effect of FDA determinations on pediatric sNDAs for antipsychotic drugs on prescribing of these products in children.

Methods: Retrospective, segmented time-series analysis using new prescription claims during 2003-2012 for three atypical antipsychotics (olanzapine, quetiapine, ziprasidone). FDA approved the sNDAs for pediatric use of olanzapine and quetiapine in December 2009, but did not approve the sNDA for pediatric use of ziprasidone.

Results: During the months before FDA approval of its pediatric sNDA, new prescriptions of olanzapine decreased for both children and adults. After FDA approval, the increase in prescribing trends was similar for both age groups (P = 0.47 for schizophrenia and bipolar disorder; P = 0.37 for other indications). Comparable decreases in use of quetiapine were observed between pediatrics and adults following FDA approval of its pediatric sNDA (P = 0.88; P = 0.63). Prescribing of ziprasidone decreased similarly for pediatric and adult patients after FDA non-approval of its pediatric sNDA (P = 0.61; P = 0.79).

Conclusions: The FDA's sNDA determinations relating to use of antipsychotics in children did not result in changes in use that favored the approved sNDAs and disfavored the unapproved sNDA. Improved communication may help translate the agency's expert judgments to clinical practice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antipsychotic Agents / therapeutic use*
  • Benzodiazepines / therapeutic use*
  • Bipolar Disorder / drug therapy
  • Child
  • Decision Making
  • Drug Approval
  • Drug Prescriptions*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Olanzapine
  • Pediatrics
  • Piperazines / therapeutic use*
  • Quetiapine Fumarate / therapeutic use*
  • Schizophrenia / drug therapy
  • Thiazoles / therapeutic use*
  • United States
  • United States Food and Drug Administration

Substances

  • Antipsychotic Agents
  • Piperazines
  • Thiazoles
  • Benzodiazepines
  • Quetiapine Fumarate
  • ziprasidone
  • Olanzapine

Grants and funding

Dr. Kesselheim’s work is supported by the Harvard Program in Therapeutic Science and the Laura and John Arnold Foundation. The funders had no role in the conception, writing, or review of the manuscript.