Paediatric Prescribing

What is the current situation?

When a medicine is launched, the extensive set of trials to determine it is safe to use and the doses are correct, are carried out on adults. In general, pharmaceutical companies do not routinely test drugs specifically for use with children.

Many medicines currently prescribed for children do not have a dosage approved by the Medicines Control Agency, so doctors are forced to rely solely on their knowledge or anecdotal evidence when prescribing, rather than basing such decisions on evidence-based guidelines.

Do other countries have the same problems and what are they doing about it?

The issue of paediatric prescribing is being investigated at European level. In December 2000, the European Health Council asked the Commission to take specific action forward. A consultation document was produced in February 2002, as part of its commitment to address the problem.

In the States specific rules and incentives to encourage clinical trials in children have been introduced, including for example, a six months extension to patent protection.

Is interest, therefore, shifting a gear?

The tide of opinion within regulatory bodies around the world is changing and pharmaceutical companies are being strongly encouraged to collect safety and efficacy data in children for new drugs which have the potential for use in children. This will, however, leave uninvestigated the large number of currently off-patent medicines which are widely used off-label in paediatric patients.

How can this be addressed?

A solution to the problem has been explored by the Action Medical Research team — a collaboration between The School of Pharmacy, Queen’s University Belfast, The Royal Belfast Hospital for Sick Children and the Alder Hey Hospital, Liverpool. Their study is entitled: ‘Provision of an evidence base for optimising drug dosage in hospitalised paediatric patients’

Professor McElnay says there are two important areas for research: pharmacokinetics — how a medicine is absorbed in the body, metabolised and distributed for example; and pharmacodynamics – what the drug does to the body, side-effect profiles etc.

This study was the first worldwide research programme to be established to systematically evaluate both elements in a range of medicines being used outside their licensed indications in paediatric patients.

What techniques were involved?

The research programme applied the technique of sparse data analysis — a novel approach which involves obtaining small numbers of blood samples from infants and children who are already receiving an adult medicine in their routine treatment.

Simultaneous to the blood sampling, the child was monitored by a trained research nurse to assess the beneficial and adverse effects being experienced. This can involve, for example, the administration of a pain questionnaire, evaluation of routine clinical laboratory data and assessment of post-operative bleeding. A custom-designed study database is then produced. The study relied on the support of nurses, doctors, pharmacists, analysts and statisticians.

How willing were parents to be involved?

For each medicine investigated, parental (and where applicable child) consent was gained, and details of the background to the study and the reasons for the research were carefully explained. This was done either by one of the hospital consultants, or more commonly by the Research Nurse employed full time on the project. There was an encouraging willingness to take part, from both parents and children.

Which medicines were featured?

Some of the drugs included: Diclofenac (for post-operative pain); Ranitidine (which help prevent stomach ulcers); Enalapril (for heart conditions); Paracetamol (in children under 3 months); Ibuprofen (in children under 6 months), and Midazolam: (a sedative).

How important are the results?

The findings will give confidence to prescribers when using the study drugs within a clinical setting. As a general rule, the doses selected by clinicians were appropriate and safe. The control of symptoms were, however, not optimal in all cases, most notably in the control of pain.

How much support has Action Medical Research been gaining?

There has been widespread support for Action Medical Research’s awareness campaign, Drug Treatment In Children: Children Are Not Little Adults.

More than 40 MPs added their name after the campaign was launched in 2000.

Andy Love MP for Edmonton says:

“This study confirms what we have known for some time — that children are not getting a fair deal when it comes to medical treatment. The quality of medical care that children receive is just as important as that for adults, yet doctors are left to guess appropriate dosages. We need a licensing system that gives doctors the information they need so that children can get the best possible treatment.

“We think it’s scandalous that there is so little evidence-based guidance on the medicines used to treat babies’, says Bengie Walden, Chief Executive of BLISS — the charity concerned with the care of premature and sick newborn babies. ‘A recent letter in the BMJ suggested that animals have better safeguards than human babies when treated with unlicensed drugs. Much more must be done to protect these very vulnerable babies, and ensure that the medicines they receive are safe and effective. We strongly support Action Medical Research’s initiative.”

(Ref: Off label prescribing in children, BMJ 2002; 325:338 10 August)