The plight of paediatric drug therapy.

The pursuit of better drug therapy for children and youth is a public health issue of worldwide concern. Health care practitioners treating children have long appreciated the limitations of research data supporting optimal therapy for their patients. It is a lamentable fact, true even in 2011, that most drugs used in paediatrics have not been adequately studied, although the level of relevant research has recently increased dramatically. International attention became focused on this issue as early as 1968, when Dr Harry Shirkey coined the term ‘therapeutic orphans’ to describe the situation of infants, toddlers and children who, in his view, were being deprived of access to properly validated modern drug therapy (1). Clearly, there are some exceptions to this alarming broad view: adequate studies have been conducted in some drug categories including antibiotics, respiratory therapies, anti seizure treatments, analgesics and vitamins. It is also true that considerable emphasis has sometimes been placed on the study of drugs intended for use in conditions relatively prevalent in childhood including, among others, infections, attention-deficit disorder, autism, asthma and seizures. Canada has been a leader in paediatric therapeutics since a ground-breaking research program started at McGill University (Montreal, Quebec) in the 1970s, which focused on neonatology, drug safety, and the development of drug biotransformation capacity in utero and in infancy. In the 1980s, the University of Toronto (Toronto, Ontario) devoted substantial resources to the fostering of paediatric clinical pharmacology at The Hospital for Sick Children (Toronto), resulting in a world-leading program with important research findings in toxicology, pharmacogenetics, anti-infective therapy, anesthesia, analgesia, oncology, respirology, neonatology and obstetrical pharmacology. In spite of Canada’s international leadership in such therapeutic areas, there has been only limited success in changing the national drug regulatory environment and in securing adequate labelling for most products used in paediatrics. Drug evaluation and regulation evolved steadily throughout the past century as a more sophisticated process of drug discovery resulted in an ever-increasing number of therapeutic entities with potential for use in younger patients. An influence of equal importance has been the recognition of unanticipated toxicities affecting children, in particular, sulfanilamide in the 1930s, chloramphenicol in the 1950s and thalidomide in 1960 (2–4). In 1962, the drug regulatory framework in the United States was overhauled by the amendments to the Food, Drug and Cosmetic Act. In spite of such progress, relatively little parallel attention was paid to drug therapy for children (5–10). Until the early 1990s, paediatric prescribers were usually left without adequate product labelling, but this situation has begun to change through efforts made in the United States and Europe to better serve children through regulatory and policy reform (11,12). Recent data in the United States suggest that most drugs likely to be commonly used in paediatric practice are now receiving appropriate research attention before licensure (13). In 2007, the European community introduced legislation requiring companies filing for licensure of new products to submit a paediatric investigation plan if there was any likelihood of use in children (14). These legislative initiatives are beginning to bear fruit in the form of appropriate product labelling of new products for therapeutic use in infants, toddlers, children and youth, although some would argue that recent progress is still insufficient to the enormity of gaps in evidence-based paediatric treatment. Because of earlier inadequacies in drug evaluation and the lack of a legislative structure to encourage drug investigation in the paediatric population, many older therapies continue to be used without being acceptably studied. This knowledge gap is likely to remain challenging for government decision makers and practitioners as well as for children and families.