17 Clinical Research in Children

Lionel D. Edwards

17.1 Background

The world population reached 6 billion in June
2000, and half of the world’s population (3 billion)
are less than 15 years old. Sadly, the mortality rate
of children in Third World countries is 10 times
higher than in the developed world. Before 1850,
half of the children born in the United States died
from infections before five years of age. The intro-
duction of sanitation, antiseptics and, in the last
century, vaccines, and lately medicines, have made
such early deaths in the United States now very
uncommon.
Today, accident is the largest killer of children,
accounting for 2500 deaths in children under five
years; this compares to 700 deaths from congenital
abnormalities, 518 from cancer and 473 from mur-
der. AIDS is the leading infectious cause of death in
the under–five-year-olds (200). The major causes of
death in the 5–14-year-olds are accidents (3500),
cancer (1053) and murder (570). Again, in this age
group, AIDS is the leading infectious cause of death
(National Center for Health Statistics, 1996).
Many of the childhood cancers are hematologic,
and great improvements in survival have been
achieved. For example, the acute leukemia survival
rate in children has risen from 53% in 1970 to 80%
by 1989 (American Cancer Society); and new

surgical techniques and new devices are improving

and sometimes correcting (even by intrauterine

surgery) many previously fatal congenital abnorm-

alities, for example hypoplastic heart.

This chapter will focus on the current regulatory

requirements, their background, the clinical study,

challenges and the clinical issues of drug research

in the pediatric population.

Still estimated that over 2500 studies in the

FDA’s pediatric subgroups needed to be conducted

over thenext threeyears (Still, 2000).This includes

completion of pediatric studies on the FDA priority

list of marketed products. Estimates of the annual

cost to the industry of these studies vary. The FDA

estimated in 1994 that $13.5–20.9 million per year

wouldbespent by industry (FederalRegister, 1998).

At a press conference, Christopher Jennings, Pre-

sident Clinton’s principal healthcare advisor, said

that pediatric label studies would only be about 1%

of the development cost of a drug. Dr Henry Miller

(1997), a former FDA Director of the Office of

Biotechnology, said that applying Jennings’ figure

will mean an industry cost of $200 million (1% of

the $20 billion spent on R&D). Dr Still, presenting

at the 36th Drug Information Association (DIA)

Annual Meeting (1999), estimated the cost at $892

million if all five pediatric subgroups were to be

studied (based on 1999 study costs).

Principles and Practice of Pharmaceutical Medicine, 2nd Edition Edited by L. D. Edwards, A. J. Fletcher, A. W. Fox and P. D. Stonier
#2007 John Wiley & Sons, Ltd ISBN: 978-0-470-09313-9