Over the last 10 to 15 years, several regulatory measures have been taken by the FDA and the European authorities to stimulate clinical development and the systematic collection of evidence in paediatric pharmacology. Legislation included the ‘FDA Paediatric Rule’ and ‘Paediatric Study Incentive’ (1997, 1998) and the ‘Best Pharmaceuticals for Children Act’ (2001). The ‘FDA Paediatric Rule’ required that all not-yet-approved medications must be studied in the paediatric population (unless the drug is unlikely to be used for children/adolescents). The ‘Paediatric Study Incentive’ granted an extension of six month market exclusivity for products studied in children/adolescents. The FDA’s Best Pharmaceuticals in Children Act’ established a process for studying both on-patent and off-patent drugs. Similarly, the European Parliament and the Council of the European Union adopted in 2006 and 2007,a legislation (Paediatric Regulation) according to which pharmaceutical companies are obliged to submit a ‘Paediatric Investigation Plan’ (PIP) as part of a drug development program for new drugs, and for new indication for approved drugs. Due to the above legislation, the number of paediatric development programs has already increased and is expected to increase considerably over the next five to ten years in all areas of paediatric pharmacology, including paediatric psychopharmacology.
In recent years, ICON has already been involved in several important paediatric psychopharmacology programs and studies. On July 31, 2012, ICON organised a free webinar with internationally recognised experts in child and adolescent psychiatry to discuss challenges and unmet medical needs in paediatric psychopharmacology. In addition, an ICON Regulatory Affairs Expert - Daphne Smyth, provided an overview of major regulatory requirements.
The legislation initiatives described above were considered necessary because paediatric pharmacology has been for many years, a neglected field for drug development. No systematic research and development was felt necessary. Drugs approved for adults were prescribed off-label, and drug doses simply adjusted according to body weight. This resulted in, at the very least, sub-optimal treatment and in some cases efficacy and safety issues. This is illustrated by the following finding in one of our paediatric programs which contradicted the traditional dose-adjustment approach (i.e. reducing doses in children): Systematic pharmacokinetic / bioavailability studies demonstrated, for a specific psychotropic drug, that doses required in children for an effective treatment were actually not lower, but needed to be higher than adult doses due to a faster metabolism in children. Although a lack of systematic research was for many years characteristic of paediatric pharmacology in general, paediatric psychopharmacology and child & adolescent psychiatry have been struggling with specific additional issues and hurdles. There have been reservations and concerns against using drugs for the treatment of behavioural and psychological disorders in children; biological factors in the development of such disorders were neglected or even questioned and pedagogic measures considered the most appropriate and sometimes only adequate choice of correcting these disorders. These attitudes have been gradually changing over recent years, at least among medical experts. Psychotherapy still plays an important role but drug treatment is increasingly recognised to be a necessary part, especially in persistent and more sever forms of mental disorders and behavioural problems. Areas of drug development likely to play a prominent role in paediatric psychopharmacology are MDD, Bipolar Disorders, Psychotic Disorders, Anxiety Disorders, ADHD, and Autistic Disorders.
Future drug development will hopefully not only result in the use of more adequate doses, better efficacy and safety profiles for the drugs used, but also bring about more convenient dose regimens and application forms that are likely to improve treatment compliance in children and adolescents.