Ethical Concerns1

According to Dr. Nelson, ethical concerns should not be a barrier to pediatric research. Although children cannot consent to participate in research studies, there is broad international agreement on three core ethical principles that should guide pediatric research:

  • Children should not be enrolled in research unless necessary to answer an important scientific question about the health and welfare of children.

  • Research involving children must be characterized by a balance of risks and potential benefits comparable to that of available alternatives.

  • Research offering no direct benefit to children must be restricted to that posing minimal risk.

Although definitions of “minimal risk” and “low risk” vary, Dr. Nelson argued that the differences are insignificant. For research with the prospect of direct benefit to the study population, every health authority uses similar language. The pertinent U.S. Food and Drug Administration (FDA) language appears in Subpart D of the Code of Federal Regulations, “Additional Safeguards for Children Involved in Clinical Investigations” (21 CFR §50.52). This language suggests that risks must be justified by anticipated benefits, and anticipated benefits and risks must be balanced in both arms of a study. The variability seen in Institutional Review Board (IRB) determinations is not driven by differences in definitions, but by the inevitable differences in individual judgments within any group of people (Sugarman, 2004). Better definitions are not likely to eliminate that variability.

According to Dr. Nelson, ethical barriers to the study of pediatric drugs fall into four categories:

  • Clinicians are willing to prescribe drugs off label without sufficient pediatric data (adults, of course, are prescribed drugs off label as well). This willingness to use drugs without sufficient data results in delays in needed research.

  • Sponsors, as expected, act in their financial self-interest. They often pursue pediatric clinical trials late in a drug’s life cycle, after its true market value has been determined. Once they have decided to conduct a trial, cost considerations may trump considerations of study design quality.

  • Academic institutions do not reward investigators for participat-


This section is based on the presentation of Dr. Robert Nelson, Associate Professor of Anesthesiology and Critical Care, Children’s Hospital of Philadelphia.

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