TABLE 1

Potential Practice, Research, and Policy Implications of Exemplar Medications Being Used Off-Label in the Pediatric Population Based on Degree of Use, Benefit–Risk Balance, and Uncertainty of the Evidence

MedicationOff-Label Use (Relative # of Prescriptions)BenefitsRisksLevel of CertaintyExample Drug and IndicationsaPotential Implications
A↑↑↑↑↓↓Azithromycin and acute otitis mediaGeneration of additional pediatric data may be necessary and sufficient.
B↑↑↑↑Antipsychotic and behavior outside of autism spectrum disorder in 2- to 5-y-oldsPolicy changes directed toward risk mitigation may be necessary, decision support to clinicians around risks and generation of additional pediatric data.
C↑↑↑↑↓↓↑↑↑Albuterol and bronchiolitisEfforts to stimulate practice change through education, dissemination, or policy change.
D↑↑↑↑↑↑↑↑Sertraline and pediatric major depressive disorderContinue ongoing surveillance for new or long-term effects (beneficial and adverse). Prompt shared decision-making about risks and benefits.
ESildenafil and pulmonary arterial hypertensionCloser monitoring of these select cases by clinicians and encouragement to collect data.
  • ↑, high; ↓, low; # of arrows, degree of increased or decreased benefit, risk, and level of certainty.

  • a The number and directionality of arrows are qualitative assessments by the authors and practicing clinicians from the Comparative Effectiveness Research Through Collaborative Electronic Reporting collaborative based on focused literature reviews and their combined clinical and research experience. The examples are provided for illustrative purposes alone, not as comprehensive reviews.