Wednesday, February 9, 2005

European Union Supports Trial Research for Children
By Julie McKeel

The European Union is one step closer to adopting US-style regulations encouraging the development of drugs designed specifically for use in children. This decision was announced by industry, clinician, and regulatory affairs representatives who met in Brussels in January for the European Forum for Good Clinical Practice.

While a final decision by Europe's lawmakers is probably more than a year away, the question isn’t whether the European Parliament and Council will adopt the proposals, but what happens after it does.

According to estimates presented at the meeting, at least half of all medicines given to children in Europe's hospitals have never been tested and authorized for use in pediatric patients. Only five medicines have been specifically studied in newborns, according to DCRI’s Dr. Barry Mangum, associate clinical professor in the department of medicine, division of clinical pharmacology.

Forum attendees were reminded that it is wrong to assume that children are simply smaller versions of adults when prescribing drugs. Their metabolism is different and varies throughout childhood. Children’s tissues and vital organs are constantly developing, and their reactions to medications as well as their ability to process drugs are complex and different from adults.

However, developing and testing drugs specifically for children is simply not profitable enough for drug companies to explore. The forum proposals aim to correct that by rewarding companies for investigating the effects of medicines on children -- even, or perhaps especially, for adult medications -- while also forcing companies to do the investigations themselves.

“Under the proposals, companies seeking approval for new medicines will either have to go to a new European Pediatrics Committee of the European Medicines with data from pediatric clinical trials, or ask the committee to grant a waiver or a deferral, “ Peter Arlett from the European Commission told Nature.com. “In return for completing studies, the makers of patented medicines will gain a 6 month 'patent extension' in Europe, rising to an extra 2 years for drugs for rare, or orphan, diseases.”

This proposal mirrors regulations introduced into the U.S. in 1997 and confirmed by Congress in the Best Pharmaceuticals for Children Act of 2002.

Concerns remain about how effective the provisions for older medicines will be in encouraging drug companies to produce medicines for children. According to Diane Murphy, Director of the FDA's Office of Pediatric Therapeutics, as of 2004, the authorization procedure had led to 17 product labels carrying new dosing recommendations, 21 with new child-specific label information, and 11 with statements that effectiveness in children had not been established.

A potential stumbling block is the limited number of trained pediatric clinical pharmacologists in Europe. This expertise is mostly found in the academic/clinical sector, and thus, as in the U.S., the pharmaceutical industry is going to have to rely on this sector for reliable data.

Informed consent presents another hurdle for the proposed regulations. Informed consent guidelines already exist for both parents and for the child, when the child is capable of understanding what is going on. But complications exist here, too, including situations involving divorced parents and egg-donor parents.

Testing drugs designed for adults to make sure they are safe for children is, however, a long way off from developing drugs specifically for children and would require massive incentives for industry. "We're at the bottom of a long, steep climb," Mangum told Nature.com.

Despite concern that some might balk at the idea of clinical trials involving babies and children, forum attendants expressed confidence that most can be won over.

While the continent's researchers and companies are nearly 10 years behind the U.S. in this area, there is a general agreement that the proposals are a good start for Europe. And Europe has the added benefit of learning from the U.S. experience.