Abstract

Children have been subjects of medical research for many centuries. Nontherapeutic experiments on mentally retarded children using radioisotopes by researchers from the Massachusetts Institute of Technology between 1944 and 1974¹; and the hepatitis studies at Willowbrook in the 1950s and 1960s² reinforced the need to recognize children as a highly vulnerable population whose interests needed to be protected during the conduct of medical research. However, striking a balance between children’s participation in research and providing them adequate protection poses a significant challenge. This difficulty has led to the exclusion of children as research subjects over the years, such that 80% of drugs in common use are not labeled for pediatric use due to insufficient studies in children.³ Hence many drugs approved for adults are being used off-label to treat children. In essence, children are being ‘experimented upon’ outside the context of controlled clinical trials, making them “therapeutic orphans.”^4,5 Since off-label drug use has the potential to harm subjects, the American Academy of Pediatrics deemed the formal study of drugs in children “a moral imperative.”⁶ In an effort to increase the number of drugs labeled for pediatric use, the United States Congress passed the Modernization Act in 1997, which provides an extra six-month period of patent protection for drugs deemed worthy of studying in children by the Food and Drug Administration.⁴ In 1998, the National Institutes of Health (NIH) issued a policy requiring children to be included in all human subject research sponsored by the NIH unless there were ethical or scientific reasons to exclude them.⁷ Similar legislation has also been passed in Europe in an effort to encourage pediatric research.⁸