Sharon Conroy, John Mclntyre, et al (Academic Division of Child Health, University of Nottingham, Derbyshire Children”s Hospital, Queen’s Medical Centre, Nottingham, UK)
Drug trials in children: problems and the way forward.
Br.J.Clin Pharmacol, 49: 93-97.
Summary : 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. Several studies have shown unlicensed and off-label drug use for hospitalized children with upto 90% of newborn infants in intensive care receiving either unlicensed or off-label treatment.
Unlicensed medicines may be those compounded in a hospital pharmacy and their quality may be variable. The term off-label refers to use of a medicine outside specifications of the product license different dosage to that recommended, in different age group, by different route or for a different indication.
Pharmaceutical companies may have been reluctant to study medicines in children, as market for children is smaller, ethical difficulties, problems with blood sampling and recruiting sufficient number of children.
A new European guidance has come into force since September 1997 in relation to clinical trials for conditions in children where there is either no or inadequate treatment. At present the guidance divides drugs into 4 categories and gives recommendations.
Blood sampling: It is considered ethical, if full informed consent is obtained from the carer or child (if more appropriate). Use of topical local anaesthetic cream has simplified this problem. Number of blood samples should be minimum. Four blood samples at appropriate time points for drugs excreted by kidneys, are adequate if adult-data and half-life are available. For newborns, microassays are essential. Non-invasive techniques like erythromycin breath test need to be developed.
The guidance regarding clinical trials in children-4 categories are :
(1)Diseases affecting children exclusively – Clinical trials in children may start before any adult human experience.
(2) Diseases mainly affecting children, or diseases having different natural history in children – Clinical trials at an early stage in clinical development.
(3) Diseases occurring in adults and children, for which there is currently no treatment – clinical trials needed following demonstration of safety and reasonable efficacy, in adults.
(4) Diseases occurring in adults and children for which treatment exists – clinical trials in children should follow completion of adult phase 3 trials.