Dr Duncan Curley of McDermott Will & Emery UK LLP examines the new European law on developing medicines for children
On 26th January 2007, the long-awaited European regulation for encouraging the development of medicines for children entered into force. Since the legislation was first proposed (1), there has been a great deal of debate and discussion about the appropriate rewards and incentives that should be made available in order to encourage clinical trials, both of new medicines for children and of existing medicinal products adapted to their specific needs. This article examines the outcome of that debate and describes the rewards and incentives now available under the Paediatric Regulation: Regulation (EC) No 1901/2006 as amended by Regulation (EC) No 1902/2006. The European Commission (EC) believes that more than 50 per cent of the medicines used to treat children in Europe have not been tested and are not authorised for use in the paediatric population.
The whole purpose of conducting clinical trials and obtaining regulatory approval of a drug for human use is, of course, to make sure that it is safe, efficacious and that it meets adequate standards of quality. However, present doses of medicines for children tend to be worked out with reference to the appropriate doses in adults – usually by reducing the adult dose based upon surface area or body weight – rather than by testing drugs in children beforehand. Yet children may respond differently to drugs that have been trialled and approved for use in adults. For example, reducing the dose of a drug in order to treat children may result in it having no therapeutic effects at all. In addition, the route and frequency of administration of a drug may change its pharmacological effect. Whilst unlicensed and off-label prescription does not necessarily threaten the health of children, there are clearly inherent risks in not properly researching the effect of medicines in the paediatric population before they are widely used. In a worst case scenario, the use of untested medicines could lead to adverse drug reactions, causing illness or even death.
A report commissioned by the EC in 2003 predicted that the costs of adverse drug reactions in children could amount to 0.1 to 0.4 per cent of total healthcare expenditure in Europe by 2015, possibly running as high as two per cent in some cases (2).
THE COST OF PAEDIATRIC CLINICAL TRIALS
The overarching policy objective behind the new legislation is, therefore, to increase the research, development and authorisation of medicines for use in children. The problem is that paediatric drug research has historically been considered expensive, involving difficult issues such as obtaining consent (both from parents and children) and ethical issues arising from uncertain long-term toxic effects.
The cost of conducting a paediatric clinical study was estimated to be between ˆ1 million and ˆ4 million in 2004 (2). The EC therefore needed to address in its legislation the question of how it was going to ensure that potentially expensive clinical trials in children would be carried out, without unduly penalising the research-based pharmaceutical industry with the imposition of a further substantial cost burden.
THE US EXPERIENCE
Fortunately, the European Commission could draw upon the US’ experience of encouraging medicines for paediatric use. By 2004, the Food and Drug Administration Modernization Act of 1997 had had the effect of significantly increasing the number of paediatric investigations of medicines, at an estimated increased cost of $61 million per drug.
The key aspect of this law was a mechanism for improving the reward for carrying out paediatric studies, by means of the intellectual property system. The law rewards drug companies for undertaking clinical studies for new drugs in children by adding an extra six months of exclusivity to the term of patent protection. The incorporation of an equivalent measure into the European law is one of the cornerstones of the new paediatric regulation.
