At present, between 50 and 90% of daily prescriptions for sick children use
"off label" drugs. Recently, legislations were introduced to stimulate the pharmaceutical industry
to investigate the pharmacological effect and safety of both new and existing medicines in
children. The quality of pediatric randomized controlled trials is often suboptimal, in part
because guidance for their design and execution is lacking. Also, evidence indicates that the
quality of reporting of randomized controlled trials is less than optimal. The aim of this survey is
to identify, classify, and appraise existing guidance on the design, conduct and reporting of
pediatric clinical trials.
We systematically reviewed all relevant methodological and regulatory literature
on standards or guidelines for clinical drug trials in children, over the period
1999-2009. The descriptives and contents of these guidelines were extracted and their quality
was appraised by a modified version of the Appraisal of Guidelines Research and Evaluation
Of 60 documents found on the internet and 3779 articles found in bibliographic
databases, 22 internet guideline documents and 18 scientific publications which addressed recommendations for pediatric clinical trials were selected. The appraisal of
these guidelines showed that the methods of research guideline development were poorly described.
Areas of pediatric research that were addressed varied greatly and empirical evidence for recommendations was scarce. Most research guidelines are limited to "what one
should aim to do" instead of "how to do it".
There is a need for readily accessible, clear guidelines on how to design,
conduct and report clinical drug trials in children in a scientifically valid and ethical way. To
enhance their acceptance, these guidelines should be developed using transparent methods with
input from investigators, regulators, WHO, and the pharmaceutical industry. Parallel
to their development attention should be paid to their active promotion, implementation,