IRBs’ special emphasis
IRBs have a duty to make sure the study is of value
to children in general and in most cases to the
patient him/herself; is robust enough to give
answers; and attempts to minimize risk and maxi-
mize benefit. In reviewing the protocol, the IRBs
should involve healthcare specialists who are
aware of the special medical, psychological and
social needs of the child, and the disease as might
be impacted by the study.
In studies conducted on diseases mainly affect-
ing pediatric patients, the development will be
entirely in pediatric patients. However, in addition
to the appropriate usual toxicology and neonate
animal toxicology, the first-in-humans studies for
toxicity and safety are usually done in healthy adult
volunteers. Clearly, however, drugs such as the
surfactants would yield no useful data from adult
testing. For these unique pediatric situations, new
measurements and end points may need to be
developed and validated. Frequently, the FDA
will involve an advisory panel to help determine
what these might be.
The use of a placebo control
Placebo control is desired whenever possible if
using a placebo does not place the pediatric
patients at increased risk. The AAP Committee
on Drugs (1995) outlined other circumstances:
No other therapy exists or is of questionable
efficacy, and the new agent might modify the
disease.
If the commonly used therapy has a high profile
of adverse events and risk greater than benefits.
When the disease fluctuates frequently from
exacerbations to remissions thus the efficacy of
the (new) treatment cannot be evaluated.
17.6 Conclusion
The ICH draft guidance on pediatric issues has
been published in theFederal Register(2000).
This guidance covers pediatric formulation, devel-
opment, ethics, regional and cultural issues, regu-
latory expectations, duration and type of studies,
and age ranges to be studied. The guidance is
similar to the FDA Final Rules (Federal Register,
1994, 1998) with the addition of a fifth group,
preterm newborn infants. It also seems better orga-
nized and informative,butthen,hindsight is always
helpful.
The face of pediatric pharmacologic medicine
has been changed. In future, for pediatricians there
will be less uncertainty and better predictive infor-
mation available; for children, safer and more
effective dosages will result. For the industry, the
added cost of research will be more than recouped
in a new global market to which previously they
could not promote their products. This is supported
by the 1998 survey by PhRMA, which showed that
medicines and vaccines in development for chil-
dren were up 28% from the previous year.
The FDA Modernization Act of 1997, the
Best Pharmaceutical for Children Act 2002
and the Pediatric Research Act of 2003 have
brought about improvements (see chapter on US
Regulations).
Meanwhile in Europe similar efforts are under-
way with the EU issuing the European Draft
Document for Pediatric Regulation. It proposes
10-year exclusivity for ‘off patent drugs if
required pediatric studies are done, and six months
for patented medicines’. This draft is currently
under consideration and comment by members
states before the EU Commission signs a final
regulation.
In addition, the ICH issued the E11 Pediatric
guideline on Federal Register 2000. This outlines
conduct of studies in children and is utilized by
many countries. This guideline also addresses
availability of formulations and labeling for
children.
As of 2004 there are 158 medicines being
actively developed for use in children, including
32 in cancer (still one of the leading causes of death
in children 1–14 years); 15 medicines for cystic
fibrosis; 11 medicines for infectious disease; and
15 new vaccines (Holmer, 2004). In addition, the
OfficeofPediatricTherapeutics has beenformedin
the FDA to monitor and enforce pediatric requests.228 CH17 CLINICAL RESEARCH IN CHILDREN