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The three decades prior to the National Commission's 1977 report Research Involving Children witnessed infamous abuses of children used as subjects for medical research in the United States. The Willowbrook hepatitis studies and the human radiation experiments conducted at the Fernald state residential school illustrate the special vulnerabilities of children to the risks involved in unethical research. In the early 1980s, moderately protectionist guidelines (the Common Rule and Subpart D) were enacted as a regulatory response to such abuses. In the mid-1990s, however, the focus shifted from protecting children from research risks to ensuring their access to the benefits of clinically validated pharmaceuticals. The failure to test drugs for their safety and efficacy in children exposed them to unsafe treatment. Lainie Friedman Ross has written Children in Medical Research: Access versus Protection against the backdrop of this shift, questioning whether the pendulum has swung too far in favor of wider access to research without adequately considering the risks associated with research on children.
Ross divides her book into four sections. The first introduces the theme of "access versus protection" both in a historical review of human subject protection from 1966 to 2005 and in a meta-analysis of the representation of minorities in pediatric research. Throughout this section—and the book—Ross maintains that minimizing the risks must be the primary focus of policies and practices relating to the participation of children in medical research. One of the more interesting conclusions she reaches through these explorations is that parents should be able to enroll their children in research that offers them no prospect of direct benefit. This suggestion is in keeping with her philosophy of constrained parental autonomy that recognizes the wide leeway liberal, democratic societies grant to parents in matters of child rearing.
Section Two raises challenges to the U.S. regulatory framework. The Code of Federal Regulations (CFR) addresses research involving human subjects in CFR 45 part 46, Federal Policy for the Protection of Human Subjects. Subpart A, known as the Common Rule (because it has been adopted by 16 federal agencies and departments in the U.S. government), deals with regulation of research with [End Page 299] human subjects. The subparts that follow provide additional regulatory protections for historically vulnerable research populations. Subpart D addresses research involving children. In its simplest form, this regulatory framework allows local institutional review boards (IRBs) to approve three categories of pediatric research based on the level of risk and the prospect of direct benefit: CFR 46.404, research involving no more than minimal risk but of no direct benefit to the participant; CFR 46.405, research involving more than minimal risk, but offering the prospect of direct benefit to the child; and CFR 46.406, research involving a "minor increment" above minimal risk and offering no prospect for direct benefit to the participant, but which likely yields generalizable knowledge about the subject's disorder or condition.
An overview of the Common Rule and Subpart D serves as a springboard for the three challenges discussed by Ross: providing greater protection for healthy children enrolled in medical research; providing informed consent, which is often a matter of parental permission and sometimes pediatric assent; and understanding the "prospect of direct benefit" in the context of phase 1 oncology trials. The discussion on the last challenge is especially timely and much debated in literature. According to Ross, federal regulations do not define "direct benefits" in the context of phase 1 studies or explain how they differ from other types of benefits. Furthermore, the possibility of direct benefit is not the primary objective of a phase 1 trial—phase 1 research is conducted to determine toxicity. If the intent of researchers in phase 1 trials is to determine toxicity, and if this intent is morally relevant, she argues that phase 1 studies cannot claim to offer the prospect of direct benefit and therefore do not fit in any of the categories approvable by local IRBs. Ross argues for the addition of a new category in the federal regulations for research with...