Safer prescribing for children

Paediatric prescribing can be precise, beneficial, and safe. It can also be confusing, based on little or no evidence of effectiveness, and can put children at risk. The nature of marketing authorisations (formerly product licences) for drugs merely enhances the paradox. They were designed as a means of obtaining approval for use by an appropriate regulatory body, usually a government agency; so the decision to apply for authorisation is influenced more by commercial than clinical considerations.¹ One result is that unlicensed and “off label” prescribing is common. Paediatricians, general practitioners, and others are torn between providing treatment which their experience and reason have deemed suitable and denying it because of the lack of research data underpinning indications, dosages, or formulations.

A study in five European hospitals showed that 39% of drugs prescribed for children were off label and a further 7% were unlicensed.² Similar studies in general practice of prescriptions for children found that 11% were off label or unlicensed in the United Kingdom, 33% in France, and 29% in the Netherlands.^3-5 Furthermore, neonatologists have little choice but to use drugs in unauthorised ways because their patients are rarely entered into trials of new preparations: 80% of infants in an Australian neonatal intensive care unit received an off label or unlicensed preparation.⁶ Such prescribing is a problem not just for doctors: patients in a paediatric isolation ward in Germany who were treated with unlicensed or off label drugs had a significantly increased risk of adverse drug reactions.⁷

Complacency about the lack of evidence based information on medicines for children is unacceptable. But several initiatives—three which should encourage high quality research and one which should provide authoritative information on prescribing—should go a long way to solving this problem.

The NHS health technology assessment programme is to commission a portfolio of research projects on medicines for children. Proposals should reach www.ncchta.org by 1 pm on 19 October 2005.

The European Commission has responded to professional and public concerns by proposing a directive on medicinal products for paediatric use.⁸ It includes establishing an expert committee to assess and approve all protocols for paediatric drug trials. This committee would consider whether studies are likely to show therapeutic benefit and would be expected to turn down those it thought would unnecessarily duplicate other work, while not delaying authorisation of medicines for other ages. In addition the European Medicines Agency has issued a draft guideline on pharmacovigilance among children.⁹

The proposed European directive on medicinal products for children has much in common with the Pediatric Research Equity Act passed by the US Senate in July 2003. This empowers the Food and Drug Administration (FDA) to require manufacturers to test medicines for safety and effectiveness in children and to establish protocols for paediatric dosing and administration. The FDA can waive such requirements when a drug is unlikely to be used in children and can defer decisions on paediatric prescribing when a drug needs urgent authorisation for adult use.¹⁰

This week sees the publication of the BNF for Children, which aims to offer sound up to date information on paediatric prescribing, much of which goes beyond marketing authorisations.¹¹ Its provenance is the British National Formulary (BNF), which has provided authoritative and regularly updated prescribing advice for the past 50 years, and Medicines for Children, a popular and much used publication of the Royal College of Paediatrics and Child Health.

The BNF for Children has been validated against emerging evidence, guidelines on best practice, and advice from a network of clinical experts. The UK Departments of Health will distribute it to all prescribers in England, Wales, and Scotland and to a limited number in Northern Ireland. An online version for England is almost ready.