Establishing Norms

Development of new treatments for children requires an assessment of both the beneficial effects and the safety of the therapy. Critical to such an analysis are comparative data about what constitutes normal values for a wide range of physiological variables. Such comparative data must be age appropriate and, frequently, disease specific. Many laboratory norms are based on easily accessible data for healthy adults. For pediatric studies, efforts must be made to ensure that laboratories processing clinical samples have age-appropriate norms. The collection of data for the development of such norms is often difficult because routine laboratory studies (e.g., chemistry profiles) are rarely performed for healthy children. The lack of normative data becomes an even greater issue for children with rare conditions. For example, to assess the potential toxicity of new drugs for premature infants or children with AIDS, it is essential to have baseline “normal-for-the-population” laboratory parameters, such as white blood cell counts and liver function test results. These children may already have abnormal white blood cell counts, which makes it more difficult to monitor the effects of drugs that may have bone marrow suppression as a toxic side effect.

An advantage of disease-specific clinical trials cooperatives or networks is their greater ability to collect age- and disease-specific normative data across multiple trials. Baseline data collected before administration of a study drug(s) are most useful for this purpose. Investigators should be encouraged to publish these data, and journals should also be encouraged to accept such publications.

Administering Interventions and Measurements

When they evaluate a pediatric protocol for potential harms and benefits and for appropriate efforts to minimize risks to child participants, IRBs should consider the qualifications and expertise of investigators and others to conduct the research, taking into account the procedures and age groups described in the protocol. They should likewise assess the appropriateness of the facilities and settings for the proposed research.

Particularly in studies involving infants and young children, the administration of interventions and measurements may lead to complications not encountered with adults. Some complications are physiological. For example, it is more difficult to draw blood from the small veins of infants or toddlers than from those of older children and adults. Furthermore, the smaller volume of blood in children sets limits on how much blood can safely be drawn. Fortunately, newer analytical methods permit accurate assays using much smaller volumes of blood than was possible in the past.

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