2.2 Definitions of off-label drug use
Neonates are defined as infants born to 28 days of age. A prescription
was defined as a drug prescribed for a patient regardless of how often
it was prescribed. All drugs prescribed to the patients were classified
according to Anatomical Therapeutic Chemical (ATC) classification
system.
The drugs were classified as label and off-label use. Off-label use is
to prescribe a licensed drug for use in an unauthorized way, which
differs from the ways specified in the Summary of Product
Characteristics (SmPC).2 The drugs were considered as
off label if the drug was used off label for age, dose, frequency, route
of administration and clinical indication. Off label for age was defined
as (1) prescribed for neonates younger than the approved age for any
indication; (2) information for adults and/or pediatrics was available,
but information specialized for neonates was unavailable; (3)
information for neonates such as ‘the safety and efficacy in neonates
have not been established’, ‘use as professionally prescribed’, ‘please
use after consulting physicians or pharmacist’ and ‘adjust dose
according to the disease and age’. The dosage was calculated by body
weight or body surface area and the actual dosage within ± 20% standard
dosage was not regarded as off label.15, 16 The
prescribed drugs were not further assessed for off-label categories for
dose and frequency once they were off label for age.
The on/off label status were evaluated via the Mcdex (version 3)
database developed by Sichuan Mcdex Pharmaceutical Software Research and
Development Company and Committee of Experts on Rational Drug Use
National Health and Family Planning Commission of The People’s Republic
of China, which contained labels of all drugs marketed by State
Administration for Market Regulation. We also assessed the on/off label
status of the drugs according to the Chinese National Formulary Chemical
and Biological Products for Children (CNFC) 2013.