Book Review

Children in Medical Research: Access versus Protection

N Engl J Med 2007; 356:876-877February 22, 2007

Article

Children in Medical Research: Access versus Protection
(Issues in Biomedical Ethics.) By Lainie Friedman Ross. 285 pp. New York, Oxford University Press, 2006. $74. ISBN: 978-0-19-927328-7

In the past decade, medical research with children has been on the rise, a result of federal legislative and regulatory incentives to include children in pharmaceutical research. Because the vast majority of prescription drugs have been tested only in adults, little is known about the safety and effectiveness of these drugs for use in children. In her examination of the regulatory landscape governing pediatric research and through case studies of several research arenas, Lainie Friedman Ross shows that the push to conduct clinical trials with children raises several ethical and policy issues that have yet to be resolved.

The federal regulatory standard for research with children establishes categories of approvable research based on the assessed level of risk (minimal risk and greater than minimal risk) in relation to potential benefits (the prospect of direct benefit to pediatric participants or no prospect of direct benefit). Within this framework, children with a disorder or condition — but not healthy children — are permitted to participate in research that offers no prospect of direct benefit and that exposes them to a minor increase over minimal risk. Ross rejects this double standard and the regulatory definition of minimal risk that focuses on the probability and magnitude of harm or discomfort that would ordinarily be encountered in daily life or during routine medical or psychological examinations.

Ross favors a definition of minimal risk proposed by Terrence Ackerman of the University of Tennessee College of Medicine. This definition replaces the “daily life” standard with one focusing on risks and harms to which it is appropriate to intentionally expose a child for educational purposes in family-life situations. Ross contends that this alternative definition of minimal risk obviates the need to distinguish between “minimal risk” and “minor increase over minimal risk,” thus allowing different children to be exposed to different degrees of risk, but not on the basis of their health status or their previous experience with medical treatment procedures. At the same time, she proposes that some at-risk classifications be included in the definition of what it means to have a “disorder” or “condition.”

After examining several topics concerning pediatric research and policy developments, Ross comes to several conclusions: parents should be permitted to enroll their children in some research offering no prospect of direct benefit, institutional review boards should not waive the requirement for parental permission for research on conditions for which adolescents can obtain medical treatment without parental permission, payment to children for participation in some research that does not offer the prospect of direct benefit is ethically permissible, constraints should be placed on parental autonomy to enroll newborns in certain predictive research, some pediatric placebo-controlled trials cannot be ethically justified, and a new regulatory category is needed for research that entails more than a minor increase over minimal risk and that offers the potential for secondary direct benefits (e.g., phase 1 oncology trials). Since this book went to press, the Department of Health and Human Services has accepted the recommendations of an advisory committee that address some of Ross's concerns about the need for greater scrutiny of studies that involve more than minimal risk and require the department's approval (through the 407 review process).

Some readers will disagree with Ross's recommendations and with her assessment that the balance between protecting children and increasing their access to clinical trials may have tipped too far on the side of access, though some of the case studies provide empirical evidence to support this claim. Moreover, it is not evident that her recommendations will result in greater protections for participants in pediatric research. Nonetheless, the book challenges everyone involved in research with children to consider whether current policies and practices provide them with adequate protection, whether additional safeguards are needed, and whether some barriers to enrolling children in medical research should be removed.

Karen J. Maschke, Ph.D.
Hastings Center, Garrison, NY 10524
maschkek@thehastingscenter.org