Only two per cent of paediatric drug trials reported
that they had established independent safety monitoring
committees that can help lead to the early detection of
adverse drug reactions, according to a major review in
the April issue of Acta Paediatrica.
Child health researchers from the University of Nottingham,
UK, carried out a detailed analysis of 739 international
drug trials published between 1996 and 2002 to see what
safety measures were in place and to monitor the levels
of adverse drug reactions.
Just under three-quarters of the trials (74 per cent)
described how safety monitoring was performed during the
study, but only 13 studies (two per cent) had independent
safety monitoring committees.
"We were very surprised by the low level of trials that
had independent safety monitoring committees and are urging
pharmaceutical companies to include these in all future
trials involving children" says lead author Dr Helen Sammons,
Associate Professor of Child Health.
"It is essential that appropriate drugs are developed
for use in children and clinical trials need to continue.
They are vital because they increase the chance of picking
up adverse reactions before drugs are introduced into
general clinical practice."
Dr Sammons and her colleagues found that:
- Seven out of ten trials reported adverse events and
a fifth of the trials reported a serious adverse event
(an untoward medical occurrence, not necessarily related
to a drug).
- Adverse drug reactions were reported in just under
37 per cent of trials, with 11 per cent of trials reporting
moderate or severe adverse drug reactions.
- Six clinical trials - which all had safety monitoring
committees - were terminated early because of significant
- Deaths were reported in 11 per cent of the trials,
but the majority were thought to be unrelated to the
- Death rates were highest in trials involving premature
babies, with 56 per cent of the 99 trials included reporting
- Other major specialities in which deaths were reported
included infectious diseases, neurology, respiratory
and kidney problems.
Only papers published in English on the Medline database
during the seven-year study period were included and the
authors excluded studies that covered HIV and cancer because
of high deaths rates from the actual diseases.
More than half of the studies (54 per cent) compared
a drug with a placebo (dummy) and a further third (35
per cent) involved a new medicine. A smaller percentage
(26 per cent) involved a direct comparison between two
established drugs. Some of the trials included adults
as well as children.
Studies reporting severe drug toxicity problems came
from a wide range of countries, including Argentina, Belgium,
Canada, Chile, China, France, India, Israel, Italy, Japan,
Netherlands, South Africa, Sweden, Taiwan, Thailand, Turkey,
UK and the USA.
Adverse drug reactions included bleeding, high blood
pressure, seizures, psychosis, suicide, acute renal failure
The researchers stress that clinical drug trials in children
are essential for the development of medicines and to
provide evidence of the best treatments for specific conditions.
But they feel that greater safety measures and awareness
of the risk is essential.
"We need to test drugs on children as the only other
options are to use unlicensed drugs or prescribe drugs
that have been licensed for adults off label - outside
the terms of their licence" says Dr Sammons.
"But we feel that the small number of studies that reported
having safety monitoring committees was unacceptable.
It is invaluable to have an independent monitor who can
swiftly question any adverse drug reactions or differences
in illness and death rates between groups taking part
in the clinical trials.
"Parents also need to be made aware of the risks of adverse
drug reactions when a child takes any medicine so that
they can make informed decisions that balance those risks
against the possible benefits the drug may provide their
"In a drug trial this should include information on the
mechanisms that will be used during the clinical trial
to safeguard the children taking part."
Dr Sammons points out that the number of paediatric drug
trials is likely to rise in the European Union, following
new legislation that provides companies with a valuable
financial incentive - a six-month extension to their exclusive
manufacturing licence for a drug if children are included
in the clinical trials. Similar legislation has been in
place in the USA for over five years and has led to an
increase in drug trials that include children.
"There is general agreement by paediatric health professionals,
regulatory authorities and the pharmaceutical industry,
as well as politicians and parents, that drug trials are
essential in order to improve drug therapies.
"We are calling for all paediatric drug trials to include
independent safety monitoring committees to ensure that
this vital work is carried in a way that minimises risks,
and maximises benefits, for the children taking part."