CALPOL, Junior Disprol and Tigylix are all children's over-the-counter medicines which have gone through clinical trials. When parents take their child or baby to a doctor, they assume any drugs prescribed will be equally safe and have been tested on the under-12s. This, however, may not be the case. "Thirty or 40 per cent of all drugs used on children have not been tested on children," estimates one consultant paediatrician at Crumlin Hospital, who preferred not to be identified (we'll call him Dr Jones). In these cases, the drugs are licensed for adults, yet are prescribed for children and babies.
A recent UK study of one neonatal intensive care unit found over 80 per cent of prescriptions were "off-label" - not licensed for use on children - and another UK study found 35 per cent of all drugs used in a paediatric intensive care unit were also unlicensed. "It is reasonable to assume that similar figures would apply in Ireland," says the chief executive of Crumlin Children's Hospital, Paul Kavanagh, although "unlicensed/ off-label use in general wards and in out-patients would be considerably lower". However, no Irish data exists.
"Drug companies won't carry out paediatric trials - it's too expensive because they'd have to duplicate large adult trials and it's a small market - there isn't enough money in it. We would love to have drug companies do tests," says Dr Jones. Forty years ago, dozens of children died in the US after taking an antibiotic, chloramphenical, which had not been tested on children. According to a report in New Scientist: "Children still face the same risks today". A study at Derbyshire Children's Hospital in England found many babies had been given higher drug doses than they should have received, which could lead to side-effects and possible death, according to Prof Imti Choonara, a paediatrician at the hospital.
Babies and children have been described as "therapeutic orphans" because, says Kavanagh: "When a pharmaceutical company makes an application to the licensing authority (the Irish Medicines Board) there is limited or no information regarding the paediatric use of the drug, and so the medicine cannot be licensed for children."
Doctors are forced into the unenviable position of having to choose whether to use a drug which has not been tested on a child, or to deprive them of useful treatment. Generally, doctors use the drugs, "if there is no evidence to show it's bad," says Dr Jones.
"It would be wrong to withhold a potentially useful drug to children because it has not been licensed," says Dr Kevin Connolly, general paediatrician at Portiuncula Hospital, Ballinasloe, Co Galway and a member of the safety and efficacy committee of the Irish Medicines Board. One consultant at the National Children's Hospital says if drugs are in general use, he will prescribe them for children: "I don't look into whether they have been tested on children".
The Children's Rights Alliance believes there is a need for greater awareness of the potentially dangerous consequences of using such medication, and would like to see a wide debate on the issue. "The Alliance recommends consideration of the idea that an onus be placed on drug companies to provide the medical profession with information on the paediatric use of medicine," says spokeswoman, Anne Shaw. The absence of clinical trials means information on the appropriate dose of a drug for a child is not available, and doctors calculate the dose based on body weight or, with young babies, on body surface area. This, however, can cause problems because, as one paediatrician comments: "Children are not small adults".
"Children metabolise drugs in a different way from adults," says Dr Connolly. "A child's slower rate of metabolism could slow down the elimination of the drug, so it is stored in the body longer. My philosophy is don't give any drugs unless you have to. I've prescribed unlicensed drugs for children but have always informed the parent and given them the option."
If clinical testing has not taken place, it is "impossible to tell whether symptoms are part of the patient's condition, or an effect of the drug," says Richard Cooke, director of the research unit at the Royal College of Paediatrics and Child Health in London. Dr Connolly accepts this difficulty and points to a "major problem" of the under-reporting of side-effects, which might alert the Irish Medicines Board to potential dangers for babies and children.
Although this is particularly important, given that unlicensed medicines are being prescribed, he estimates that under 10 per cent of side-effects in children are reported. A further problem, he believes, is the "grey area" of adolescents as, for purposes of prescribing, the over-12s are classed as adult, yet do not metabolise drugs in the same way as adults.
Despite the widespread use of off-label drugs, Irish paediatricians appear to be cautious in their prescription. "Such uses are informed and guided by a respected and responsible body of medical opinion," says Kavanagh. Irish doctors are benefiting from long-term use of unlicensed drugs in the US and UK: "It's not like we're using them for the first time. We wouldn't use any drug unless it was proven to work in a big centre abroad," explains one paediatrician.
Although parents would like to see more clinical trials, one problem is that relatively few parents are willing to volunteer their children as "guinea pigs" - a UK trial into a meningitis vaccine has been delayed because of a lack of volunteers aged three to four.
The situation may improve as pressure builds in Europe and the US to force drug companies to conduct trials on infants. New US legislation will ensure the FDA is provided with information on the paediatric use of any medicine that may be widely used by children - which will benefit babies and children worldwide.
The support and lobbying group, Children in Hospital Ireland (which had no idea off-label drugs were being prescribed until informed by The Irish Times) is very concerned. According to development director, Mary O'Connor: "We expect our paediatricians to ensure appropriate prescribing for their child patients. . . We are currently campaigning for a comprehensive review of the provision of care for sick children. An issue such as this highlights the need for such a review."