Objective: To determine the extent of use of unlicensed and off label drugs in children in hospital in five European countries. Design: Prospective study of drugs administered to children in general paediatric medical wards over four weeks. Setting: Children's wards in five hospitals (one each in the United Kingdom, Sweden, Germany, Italy, and the Netherlands). Subjects: Children aged 4 days to 16 years admitted to general paediatric medical wards. Main outcome measure: Proportion of drugs that were used in an unlicensed or off label manner. Results: 2262 drug prescriptions were administered to 624 children in the five hospitals. Almost half of all drug prescriptions (1036; 46%) were either unlicensed or off label. Of these 1036, 872 were off label and 164 were unlicensed. Over half of the patients (421; 67%) received an unlicensed or off label drug prescription. Conclusions: Use of off label or unlicensed drugs to treat children is widespread. This problem is likely to affect children throughout Europe and requires European action. Many drugs are not tested in children, which means that they are not specifically licensed for use in children Licensed drugs are often prescribed outside the terms of the product license (off label) in relation to age, indication, dose of frequency, route of administration, or formulation Over two thirds (67%) of 624 children admitted to wards in five European hospitals received drugs prescribed in an unlicensed or off label manner 39% of the 2262 drug prescriptions given to children were off label The problem of off label and unlicensed drug prescribing in children is a European problem that requires European action

Objective To explore the evidence available of poor-quality (counterfeit and substandard) medicines in the literature. Design Systematic review. Data sources Databases used were EMBASE, MEDLINE, PubMed and the International Pharmaceutical Abstracts, including articles published till January 2013. Eligibility criteria Prevalence studies containing original data. WHO definitions (1992) used for counterfeit and substandard medicines. Study appraisal and synthesis Two reviewers independently scored study methodology against recommendations from the MEDQUARG Checklist. Studies were classified according to the World Bank classification of countries by income. Data extraction Data extracted: place of study; type of drugs sampled; sample size; percentage of substandard/counterfeit medicines; formulations included; origin of the drugs; chemical analysis and stated issues of counterfeit/substandard medicines. Results 44 prevalence studies were identified, 15 had good methodological quality. They were conducted in 25 different countries; the majority were in low-income countries (11) and/or lower middle-income countries (10). The median prevalence of substandard/counterfeit medicines was 28.5% (range 11–48%). Only two studies differentiated between substandard and counterfeit medicines. Prevalence data were limited to antimicrobial drugs (all 15 studies). 13 studies involved antimalarials, 6 antibiotics and 2 other medications. The majority of studies (93%) contained samples with inadequate amounts of active ingredients. The prevalence of substandard/counterfeit antimicrobials was significantly higher when purchased from unlicensed outlets (p<0.000; 95% CI 0.21 to 0.32). No individual data about the prevalence in upper middle-income countries and high-income countries were available. Limitations Studies with strong methodology were few. The majority did not differentiate between substandard and counterfeit medicines. Most studies assessed only a single therapeutic class of antimicrobials. Conclusions The prevalence of poor-quality antimicrobial medicines is widespread throughout Africa and Asia in lower income countries and lower middle-income countries . The main problem identified was inadequate amounts of the active ingredients.

Objective: To determine the extent of use in children in hospital of drugs that are not specifically licensed for use in children (unlicensed) and of drugs that are used outside the terms of their product licence that apply to indication, age, dose, or route of administration (off label). Design: Prospective study of drugs administered on paediatric medical and surgical wards for 13 weeks. Setting: Regional children's hospital. Subjects: Paediatric inpatients in medical and surgical wards. Main outcome measures: Comparison of the use of each drug with its product licence to determine whether the drug was used in an unlicensed or off label manner. Results: 2013 courses of drugs were administered to 609 paediatric patients in 707 admissions. 506 (25%) of the drug courses (prescriptions) were either unlicensed (139) or off label (367) uses. In 256 (36%) of the 707 admissions patients received one or more courses of an unlicensed or off label treatment in hospital. Conclusions: Use of drugs in an off label or unlicensed manner to treat children is widespread. Drugs are more likely to be used in an off label manner than in an unlicensed manner. Children in hospital are often treated with drugs not specifically licensed for use in children (unlicensed), and drugs are also used outside the terms of the product licence that apply to indication, age, dose, or route of administration (off label prescribing) In this study 36% of children in 707 admissions received drugs prescribed in either an unlicensed or off label manner Off label drug prescribing was more common than unlicensed drug prescribing All drugs used to treat children should be subjected to the licensing process to ensure their quality, safety, and efficacy The Medicines Control Agency, the pharmaceutical industry, and the NHS need to address the issue of drugs being used in these ways