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.