It is reassuring that the majority of Scottish paediatricians are aware of the concept of off label prescribing (p XXX).¹ The term off label relates to the use of a medicine in a manner different from that recommended by the manufacturers in their product licence.² A formal classification system for the different types of off label and unlicensed drug use was described in 1997. In a period of a few years, several studies confirmed that off label drug prescribing was a significant problem in children in hospital,³ in neonates,⁴ and in primary care.⁵

The main reason for carrying out these epidemiological studies was to highlight the fact that medicines used in children have not been scientifically evaluated to the same extent as those used in adults.^6,7 Groups such as the European Network for Drug Investigation in Children have highlighted that this is a problem in different European countries⁸ and subsequent studies have shown that it is a worldwide problem.⁹ Off label prescribing is associated with a greater risk of drug toxicity.¹⁰ This is to be expected as the licensing process is carried out to ensure the efficacy and safety of medicines.

EUROPEAN LEGISLATION

The political response to the problem of off label prescribing in children has been discussed both nationally and at a European level. Legislation is currently being proposed that would hopefully improve the scientific study of medicines in children.¹¹ This proposed legislation will offer a financial incentive to the pharmaceutical industry as it is accepted that the cost of studying medicines in children is greater than in adults. Legislation in the USA has been successful in ensuring that more medicines are licensed for paediatric use.¹² Concerns have been raised, however, that the types of medicines studied are those that generate the greatest profits rather than address the clinical needs of children.¹³

The proposed European legislation recognises this point and suggests the establishment of a paediatric committee.¹¹ It is essential that the members of the paediatric committee are advocates of children and ensure that the medicines studied are those that will improve patient care. The majority of Scottish paediatricians are prepared to participate in clinical trials.¹ A weakness of the Aberdeen study, however, is that it did not try to differentiate between clinical trials of medicines for conditions where treatment is currently unsatisfactory and clinical trials of “me-too” medicines.

A major weakness in the proposed European legislation is the lack of funding for Medicines Investigation for the Children of Europe (MICE). This was in the original proposal but was unfortunately dropped owing to differences over who should fund it. The creation of a fund to ensure research and development of off patent medicines would significantly benefit children.

DEVELOPMENTS IN THE UNITED KINGDOM

There have been three major developments within the UK over the last few years. The publication of the BNF for Children following on the success of Medicines for Children will hopefully result in safer prescribing of medicines. The establishment of a Medicines for Children Research Network should facilitate the performance of clinical trials. The UK is unique in that it now has a formally recognised training programme in paediatric clinical pharmacology.¹⁴ The first fully accredited trainee has recently completed her training. Paediatric clinical pharmacologists working alongside other paediatric health professionals have helped to ensure that medicines are used more safely and effectively in children.

TRANSPARENCY

As the number of paediatric clinical trials increases it is essential that the information from these trials is made readily available. The European Commission has already funded a European Paediatric Clinical Trials Register (www.dec-net.org).¹⁵ This is the only paediatric clinical trials register worldwide.¹⁶ There is no charge for investigators who wish to enter their trial onto the register. The European Paediatric Clinical Trials Register is freely accessible to both paediatric health professionals and the public. It is essential that information regarding paediatric clinical trials remains open and accessible to all. We have seen the problems associated with the lack of publication of important clinical information by the pharmaceutical industry,¹⁷ and paediatric health professionals have a duty to children to ensure that this information remains in the public domain.

SAFETY

It is important to remember that the rationale for the European legislation and the establishment of research networks to perform clinical trials in children is to improve the evidence basis on which medicines are used in children. This should hopefully result in the safer and more effective use of medicines. One needs to be aware that adverse drug reactions (ADRs) may occur during the course of a trial.¹⁸ If such ADRs do occur, then it is essential that consideration is given to stopping the trial. Many clinical trials incorporate the establishment of a data monitoring committee/independent safety monitoring board.¹⁹ Such a committee has the responsibility to evaluate suspected ADRs and also to terminate the trial if this is felt appropriate. Every single clinical trial does not require such a committee but if there is any likelihood of significant toxicity then the creation of such a committee is essential. The responsibility for safe clinical trials in children rests primarily on paediatric health professionals rather than on the pharmaceutical industry or the regulatory authorities. These are exciting times in relation to the development of medicines for children but it is essential that the safety of children in clinical trials is paramount.