In 1959, James Sutherland, a pediatrician in Cincinnati, reported in the AMA’s American Journal of Diseases of Children on the deaths of three newborn infants who had been given “moderately large” amounts of the antibiotic chloramphenicol.
First marketed in 1949, chloramphenicol was the first broad-spectrum antibiotic, and quickly became widely used. Sutherland’s report, however, prompted investigations that eventually led to a grim conclusion: hundreds of newborns across the country had died from the administration of a drug that pediatricians believed was going to help prevent illness and death.
The fundamental problem: chloramphenicol, like virtually all other drugs at the time, was never tested in infants before it was approved for sale. Only later was it discovered that neonates lack the liver enzyme needed to break down and excrete the drug. The use of chloramphenicol in newborns ended relatively quickly following Sutherland’s first report, but, unfortunately, the practices that led to this tragic episode continued. Even today most prescription drugs have never been clinically studied for use in children, even though they are routinely prescribed to treat them. Recent legislation has improved the percentage of drugs that have been tested in some section of the pediatric population, from around 20% to an estimated 50%, but these studies do not include all age groups and fewer than 10% have ever been studied in neonates.
Since its founding, our clinical research team has been deeply involved in the long-standing effort to improve these figures by conducting, or collaborating on, research in children and infants. “Pediatric research is difficult,” says Staff Vice President of Research Operations, Julie Miller. “Fundamental challenges with dosage, routes of administration, informed consent, recruitment, and follow-up must be overcome and safety at every point must be ensured. We have developed the expertise to meet these challenges and has contributed greatly to progress in this field.”
Drug manufacturers have long avoided conducting clinical trials in children, not simply because of the aforementioned challenges, but because the pediatric population is often a small piece of a drug’s intended market and because liability concerns are amplified where children are concerned, since they include both injury and lifetime earnings potential calculations.
Only in the 21st century has federal legislation been passed encouraging manufacturers to invest in pediatric research. The Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA), for example, were enacted in 2002/2003 and extended in 2007.
Expanded studies have led to labeling changes in hundreds of pediatric medications, including new dosing amounts or dosing changes, lists of drugs known to be ineffective in children, new or enhanced safety data, and expanded approvals to cover a new age group. The FDA’s Office of Pediatric Therapeutics (OPT) also maintains a safety reporting page detailing information on products that have been tied to problems that specifically relate to children.