Phase I research and the meaning of direct benefit

In this article, I examine whether Phase I pediatric oncology trials offer “the prospect of direct benefit,” a concept found in Subpart D of the Code of Federal Regulations (CFR), the guidelines that provide additional protections to pediatric research subjects. In research that offers the prospect of direct benefit, children can be exposed to greater risk than in other research and their dissent can be overridden. I argue that Phase I trials do not offer the prospect of direct benefit and classifying them as if they do fails to acknowledge the moral relevance of the researchers’ intent. In Subpart D, research that does not provide the prospect of direct benefit can be approved locally if it does not expose the children to more than a minor increase over minimal risk. If the risks are greater, the research must be approved nationally. To avoid the need for national review for Phase I oncology trials, I propose a new research category that incorporates the concept of “secondary direct benefit.” In this category, the child’s dissent would be dispositive. This new category would improve the protections provided to children by incorporating intentions into Subpart D, the absence of which is a serious flaw in our current regulatory schema.

Abbreviations:  CFR, Code of Federal Regulations , IRB, Institutional review board , MTD, Maximal Tolerated Dose