50 Years Ago in The Journal of Pediatrics: Editorial Comment: Therapeutic Orphans

Abstract

Shirkey H. J Pediatr 1968;73:119-20 Both the drug laws of 1938 and 1962 were catalyzed by pediatric tragedies—the deaths from sulfanilamide elixir made with the untested but toxic diethylene glycol and the birth defects, particularly phocomelia, from maternal ingestion of thalidomide, respectively. The result was that drugs introduced after 1962 had to be tested in children or had to carry an “orphaning clause,” stating it was not recommended for children. In 1968, Harry Shirkey, a pediatrician and pediatric pharmacologist, criticized the prevailing climate “created by present regulations of human experimentation [that] makes drug testing difficult” and urged all pediatricians and pediatric subspecialists to take on the “responsibility for developing active programs of clinical pharmacology and drug testing in infants and children” lest children become “therapeutic orphans.” More than 25 years would pass before the National Institutes of Health would create the Pediatric Pharmacology Research Unit Network to support pharmaceutical testing of children (1994). At that time, nearly 80% of drugs lacked a pediatric label.1Christensen M.L. Chesney R.W. Has the ‘therapeutic orphan’ finally been adopted?.J Pediatr Pharmacol Ther. 2003; 8: 175-176PubMed Google Scholar Between 1997 and 2002, new federal laws and regulations “increased both the number of medications in pediatric clinical trials and the number that are labeled for use in children.”2Steinbrook R. Testing medications in children.N Engl J Med. 2002; 347: 1462-1470Crossref PubMed Scopus (193) Google Scholar The new drug testing was encouraged by both a carrot and a stick.2Steinbrook R. Testing medications in children.N Engl J Med. 2002; 347: 1462-1470Crossref PubMed Scopus (193) Google Scholar The carrot was the “pediatric exclusivity provision,” which granted an additional 6 months of patent protection or market exclusivity for new molecular entitles voluntarily tested in children. The stick was the “Pediatric Rule,” a requirement by the Food and Drug Administration that, in some circumstances, pharmaceutical companies would be required to test their molecular entitles to get approval from the Food and Drug Administration. Although this regulation was struck down, Congress passed other legislation. By 2002, new policies from the National Institutes of Health and Congressional regulations promoting pediatric research led Christensen and Chesney to proclaim that the “‘Therapeutic Orphan’ has finally been adopted.”1Christensen M.L. Chesney R.W. Has the ‘therapeutic orphan’ finally been adopted?.J Pediatr Pharmacol Ther. 2003; 8: 175-176PubMed Google Scholar The adoption was further solidified by the enactment of the Food and Drug Administration Safety and Innovation Act in 2012, which made these mandates permanent, although funding comes up for renewal every 5 years.