Meetings

British National Formulary

The issues surrounding better medicines and prescribing for children were discussed at a BNF conference last week. Lin-Nam Wang (on the staff of The Journal) reports

The BNF prescribing excellence conference, “Good medicine for children” organised by the British National Formulary, the British Medical Association and the Royal Pharmaceutical Society took place at the Commonwealth Institute, London, on 18 May

Challenges of medicines for children

Since legislation to increase the range of licensed medicines for children was passed in the US, the Food and Drug Administration (FDA) has requested over 660 paediatric studies. Similar legislation is in development in the EU so, perhaps, there are lessons to be learnt from the US. Robert Ward, professor of paediatrics and director of paediatric pharmacology unit, University of Utah, Salt Lake City, described his experiences of post legislation progress and problems. So far in the US, marketing exclusivity has been granted to 97 drugs (as an incentive for providing new data) and there have been significant label changes. For example, before pharmacokinetic studies were conducted, inappropriate doses of gabapentin were being used to treat seizures in young children.

However, with these potential advances come challenges, Professor Ward warned. First is the issue of increased workload on regulatory bodies. In the US, this was compounded by a freeze on hiring staff when the legislation was passed so that paediatric experts at the FDA found themselves working overtime. Good study design is also a challenge. “We see study designs coming to our clinical trials programme that clearly have no paediatric input,” he said. For example, a study that requires 10ml blood samples to be taken several times a day would, clearly, not be appropriate for children. Other issues affecting trials to find better medicines for children include the use of placebos and obtaining consent from children.

Another challenge is disseminating the information from studies so that it becomes incorporated into paediatric practice. One way in which this has been approached in the US is to offer continuing education credits to practitioners who review label changes on the American Academy of Pediatrics website.

Philip Green, director of education and registration, Royal Pharmaceutical Society, said that although the rational evaluation of medicines use in children was of great value, he wondered if, given the costs associated with licensing, there was a risk of inhibiting intelligent leaps of faith in the use of medicines, encouraging more defensive medicine and, perhaps, disadvantaging patients as a result. “People will say this is not licensed so I am not going to use it,” Mr Green suggested. However, Professor Ward said he did not think this would happen. Paediatricians would continue to have to prescribe off label because once patent protection has expired, discovering that there is a new use for a drug seldom changes the label in the US. For example, sildenafil is currently being studied in pulmonary hypertension in children — a use never conceived of in the licence.

The requirement for new drugs in the US to be studied in children was an enormous step forward. Although it is not known just how productive this will be, the shift in attitude was important. As the quality and quantity of data improves, perhaps we will get to the point where people can say “most drugs are labelled, therefore I should avoid using one off label” but Professor Ward thinks we are at least a decade away, if not more, from this.

Despite the advances stemming from the legislation, areas that will remain challenges to medicines for children include dosage formulation and measuring pain relief in preverbal children, Professor Ward predicted.

Drugs which should be studied first

There are not enough sites and investigators to conduct studies, so a major challenge is the question of which medicines should be looked at first. The US legislation required a prioritised list of drugs but this involved enormous effort, Professor Ward said. For example, how do you rank common childhood illnesses versus a rare inborn error of metabolism that occurs in 1 in 15,000 children, but which may be lethal, he asked. Professor Ward did not think that prioritisation added much value or stimulus to the study programme. He said that almost every study undertaken yielded helpful information for paediatric therapy, so he advised the UK not to follow the prioritisation aspect of US legislation.

The issue of prioritisation resurfaced during a later session at the conference. Brian Gennery, consultant pharmaceutical physician, Gennery associates, said he thought it would still be worthwhile giving priority to the relatively small number of products that occupied a high proportion of prescriptions, such as, anaesthetics used for children in hospital. Julia Dunne, specialist in paediatric issues, Medicines and Healthcare products Regulatory Agency, said that the last UK priority list had 400 products, but deciding which criteria to use and prioritising to a top 20 (a workable number) is difficult. Developing a priority list at European level would be even more difficult because different medical practices come into play. However, Dr Dunne added: “In the UK, we are thinking of focusing on a ‘quick and dirty’ 10 or 20 drugs, possibly, in terms of paediatric formulations.” The MHRA could talk to companies who are interested in developing a paediatric formulation where none exists at the moment, she suggested.

What to do with old medicines

Concern was also expressed that studies and licensing of older medicines (eg, bupivacaine) for use in children will be neglected because the EU legislation offers little incentive for work in this area. Dinesh Mehta, executive editor, British National Formulary said it was disconcerting that there are lots of older medicines that are used frequently in children and yet they are not licensed. If industry has no incentive to apply for licences, perhaps it is the regulators that should take responsibility, he said. “It is sad that something like salbutamol nebuliser is not licensed for use in younger children and yet lots of people use it,” he commented. Mr Mehta suggested that when there is an established practice — where the product has been used in a particular way for dozens of years and practitioners are confident about using it — perhaps these drugs should be given product licences of right. At least this would regularise practice, he said.

Public opinion

Another concern aired was the role of the public. People need to be made more aware of challenges in paediatric illnesses. “One of the challenges we face is that many adults do not seem to realise that children become sick with serious illnesses and that they may require treatment similar to adults, Professor Ward said. Headlines such as “Experimenting on children — the deadly risks” lead to public misperceptions. “That risk can either be in a study or it can be in clinical care, but the close monitoring and controls associated with drug studies can reduce that risk,” he said. That off label treatment is acceptable also needs to be understood. Children will remain second class patients without more studies to provide rational treatments, Professor Ward concluded.