Drug trials in children: problems and the way forward.

The drug-licensing system was introduced with the Medicines Act of 1968, following the thalidomide disaster, with the aim of ensuring that medicines are safe, effective and of high quality. There is increasing concern from the pharmaceutical industry, paediatricians, paediatric pharmacists and the Government that many medicines routinely used in children have not been formally evaluated by this system. Such use is therefore not supported by the assurances that the process brings. A joint report was produced in 1996 by the British Paediatric Association (now the Royal College of Paediatrics and Child Health) and the Association of the British Pharmaceutical Industry. This described in detail the current unsatisfactory situation and made specific recommendations for a way forward [1]. Since then several studies have documented the extent of unlicensed and off-label drug use in critically ill children, paediatric medical and surgical inpatients and neonates [2–4]. These studies all show that unlicensed and off-label drug use is a frequent occurrence for children in hospital with up to 90% of newborn infants in intensive care receiving either unlicensed or off-label treatment. Unlicensed medicines may be those compounded in a hospital pharmacy department or by a ‘specials’ manufacturer due to a lack of licensed alternatives. These medicines may not necessarily undergo the rigorous quality testing procedures that a licensed preparation must, and their quality may be variable. The term off-label refers to the use of a medicine outside the specifications of the product licence [5]. This covers medicines used at a different dosage to that recommended, in different age groups, by a different route or for a different indication. These off-label uses may be based on reliable published data, in which case prescribers can feel confident in using medicines in an off-label manner since this practice would be supported by peer review. In other instances they may rely more on the experience of the paediatrician or pharmacist, or drug information resources such as those of DIAL (Drug Information Advisory Line, Alder Hey Children’s Hospital, Liverpool). They are less likely to be supported by extensive clinical trial information, as would the manufacturer’s recommended uses of a licensed preparation.