Background on pediatric research

In this section you will find background information on paediatric research.

Legislation

Introduction
Before any medicine is authorised for use in adults, the product must have undergone extensive testing including pre-clinical tests and clinical trials to ensure that it is safe, of high quality and effective.

The same may not be true for medicines used to treat children. Over 50% of the medicines used in children have not been studied in this age group. In the European Union, the paediatric population (0-18 years) represents about 100 million people, 20% of the total population. This is a vulnerable group with developmental, physiological and psychological differences from adults, which makes age and development related research particularly important.

The absence of suitable authorised medicinal products to treat conditions in children is an issue that has been of concern for some time. Pharmaceutical companies have been reluctant to invest in developing specific treatments or adapting existing medicines to meet the needs of the paediatric population, mainly because the market is small and therefore of lower commercial interest and the studies can be difficult, long and expensive. In addition, developing a suitable formulation which can provide an exact dose, for example a syrup, may be technically difficult and expensive on an industrial scale.

This often leaves no alternative to the prescriber than to use ‘off-label’ and unauthorised products, without evidence-based information to guide prescribing and give information about the risk-benefit assessment.

Recent Developments
In recent years there has been an important shift in opinion, both in the US and Europe, about conducting clinical trials involving children. Acquiescence in this unsatisfactory situation is no longer regarded as tenable and the lack of such trials is now seen as the major ethical problem.

In the US, legislation has gradually been introduced since 1997 which now provides financial incentives to companies to undertake clinical trials on products used in the treatment of children whilst the products are still “patent protected” (Better Pharmaceuticals for Children Act 2002). The Act also provides for research on older off-patent medicines through a priority list developed by the National Institutes of Health (NIH). Although similar previous regulations have resulted in some success, there are a number of important children’s diseases where trials have not been conducted because of an insufficient financial incentive.

There are numerous examples of drugs often used in paediatric patients which have not been adequately studied in children, including: proton pump inhibitors which have limited indications for children but no suitable dosage form; phytomenadione for partial reversal of warfarin therapy; treatment or prophylaxis with low molecular weight heparin for thrombosis; antihypertensive medicines; clonidine for sedation in Paediatric Intensive Care Units (PICUs) and melatonin for sleep disturbance. For this reason, the US has introduced a legal obligation for companies to conduct trials with medicines for children where there is a therapeutic need, the Better Pharmaceuticals for Children Act 2002.

An European regulation, the Regulation of the European Parliament and of the Council on Medicinal Products for Paediatric Use, has been developed and accepted by the European Commission. This has established a system of requirements and incentives aimed at satisfying the need for medicines that are appropriately formulated and authorised for the treatment of children. This legislation has become law as per January 2007.