Pediatrics: Clinical studies improve safety

Small children rarely die of a stroke. They also suffer more rarely from high blood pressure than adults. But heart problems, cancer and asthma can make life almost unbearable even for babies and require many different forms of treatment. Usually, drugs are then all that can help. But this is precisely where the problem lies: few drugs have yet been tested in clinical studies for the 0-to-17 age group.

Nevertheless, if they are to alleviate the suffering of children and adolescents, pediatricians often have no choice but to prescribe their little patients drugs that have only been tested and approved for treating adults. In such cases the physicians concerned usually adjust the dosage downwards to correspond with the child's body weight. They also rely on their experience in treating rare diseases. However, this practice poses risks, because children are not little adults and often respond to drugs differently than adult patients.

Clinical trials on minors were controversial for a long time in the European Union. However, a recent EU-wide regulation created clarity in January 2007. Before applying to the respective authorities for marketing approval for an active substance , pharmaceutical companies must now also submit study concepts for clinical trials involving children of all the age groups that can theoretically be affected by the disease concerned. The aim is to guarantee the effectiveness, safety and tolerability of the products in the pediatric field, too.

The Pediatric Committee (PDCO) of the European Medicines Agency (EMA) determines the age groups for which separate clinical trials must be carried out in Europe. For pharmaceutical companies this means that they must conduct additional studies during drug development.

How a drug is absorbed, distributed in the body, and finally excreted in humans always partly depends on the patient's age. The dosage of a medicine for children cannot simply be derived from the data for adults, because certain organs, such as the liver or the kidneys, are not yet fully developed in children and adolescents. The body's composition is also different from that of adults in terms of muscle, fat and water. Compared to older children and adults, premature and newborn babies, for example, have less stomach acid and bile, and fewer of the liver enzymes that break drugs down.

Studies are therefore needed to determine for each age group whether a drug is effective, well tolerated and correctly dosed. The ICH Guideline of the International Conference on Harmonization distinguishes between five developmental stages: preterm newborn infants, term newborn infants, infants and toddlers, children, and adolescents.

But not only drug dosages, but also the forms of administration need to be better adjusted to the child's organism, because many tablets that might be helpful are simply too large for babies and toddlers to swallow. Accordingly, products for children must also be developed in child-friendly dosage forms such as mini-tablets, oral liquids or infusions.

Bayer HealthCare Pharmaceuticals has set up a special Pediatric Advisory Group to implement the EU Pediatric Medicines Regulation. Representatives of different disciplines work together in this group to help ensure compliance with the extensive requirements and adapt internal processes to the demands of pediatric pharmaceutical development.

The group supports the various Bayer project teams in the general planning of pediatric development, as well as the development of study approaches and testing plans. In order to better adapt drugs and dosage forms to the child's organism, the Advisory Group deals with a range of questions: At what point in the development of a drug can it be decided whether it is also meaningful to use the drug in children? What information is then needed in order to develop this drug for children? What clinical studies in children are needed to obtain this information? When should they start?

Bayer HealthCare's first pediatric test plans were approved in 2009, and related study programs began with young patients a year later.

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