Regulation of drugs for children in Europe

Over the past 10 years, studies have shown widespread use of unlicensed and off-label drugs to treat children in hospital and in the community.1 2 A prospective European study showed that two thirds of children in hospital received at least one unlicensed or off-label drug, and almost half of all drug prescriptions for these children were either unlicensed or off label.1 Subsequent studies confirmed that the use of unlicensed and off-label drugs is more likely to be associated with drug toxicity.3

In 1999, concerns were raised about children in Europe receiving unlicensed or off-label drugs instead of ones that have been scientifically evaluated and licensed.4 In December 2006, after extensive consultation, the European parliament approved legislation that should improve the regulation of drug treatment for children (regulation number 1901/2006 on medicinal products for paediatric use).

The legislation aims to ensure that drugs used for children are subject to high quality research that is ethical and appropriately authorised. It will also provide better data on the benefits and harms of drugs used in infants and children. This will hopefully be achieved without subjecting children to unnecessary clinical trials and—as authorisation for medicines in children can take longer than in adults—will not slow down the introduction of new drugs for adults.5

It is more expensive to develop drugs for children than for adults. Children need tailored formulations; for example, suspensions for young children and infants and ampoules containing appropriate drug doses for children of different weights.6The importance of appropriate formulations for children has been recognised by the World Health Organization, which launched a new initiative last week to improve children’s access to safe and effective medicines.7

The European legislation provides financial incentives for the drug industry to study drugs in children. Drug companies will have to develop and agree a paediatric investigation plan for an individual drug with the European Medicines Agency. On completion of the study, the patent will be protected for an extra six months through an extension of the supplementary protection certificate. For older medicines not covered by a patent, a paediatric investigation plan can still be agreed. On completion of the study, the company can apply for a “paediatric use marketing authorisation,” which would allow 10 years of data protection by a patent.5

The financial incentives are considerable, but experience in the United States has shown that the drug industry is more likely to study drugs that are prescribed extensively in adults and generate the most profit than those that infants and children require clinically.8 The European Medicines Agency and its paediatric committee will be responsible for ensuring that the drugs studied will benefit children and will not just provide the most profit to drug companies.

A European register of clinical trials of drugs for children will be established, and the results submitted to the regulatory agency will be made public. This transparency is essential, as a database of paediatric clinical trials only accessible to the European Medicines Agency would not benefit children in Europe.

The legislation is aimed primarily at the drug industry. To ensure that clinical trials in children of all ages are designed and performed with safety as a priority, the industry will need to work closely with paediatric health professionals. National networks are being set up to facilitate the development of clinical trials; the French network of paediatric clinical investigation centres is the most well established of these and has been involved in more than 200 clinical trials in the past three years.9

Clinical trials of drugs are needed in many areas where the drug industry has no interest. In the United Kingdom, the National Health Service has invested heavily in funding clinical trials in these areas through the health technology assessment programme. This funding has had the additional benefit of involving more academic units and hospitals in paediatric clinical trials. It is anticipated that funding on a European level will be available through framework programme 7—the current programme for funding scientific research within the European Union.

The scientific study of drugs in children is the basis for a new subspecialty of paediatrics—paediatric clinical pharmacology—which has a recognised training programme in the UK.10 Paediatric clinical pharmacologists have played a key role in documenting the use of unlicensed and off-label drugs in children and the risk of drug toxicity.1 11 They have been involved in the design of clinical trials in children, which usually require different approaches to trials carried out in adults.12 A recent survey, however, identified only 18 paediatric clinical pharmacologists in Europe.13 Only four countries (Finland, France, Germany, and the UK) had more than one paediatric clinical pharmacologist. Hopefully, the new legislation will stimulate scientific interest in the study of drugs in children and increase the number of paediatric clinical pharmacologists in Europe.