EDIATRICIANS OFTEN MUSTtreat children in the absence of sufficient data. 1 For example, approximately 70% of all medications do not include sufficient data for use in children. 2,3 To provide the necessary data and to ensure medical interventions are safe and effective for children, it is necessary to conduct clinical research with children. 4,5 Currently, more than 1900 clinical trials are approved for children in the United States. 6 Food and Drug Administration (FDA) requests have led to proposals to enroll another 38 000 children in clinical research. 7 One FDA request led to a series of studies, enrolling thousands of children, to establish a safe and effective dose of ibuprofen for infants. 8 Another FDA request led to studies assessing whether the combination of lopinavir and ritonavir, proven effective in adults, is safe and effective in children with human immunodeficiency virus infection. 8 Ethical guidelines for pediatric research must balance the protection of individual children with the importance of allowing research needed to improve pediatric medicine. 9-13 Federal regulations 14,15 attempt to achieve this balance by empowering institutional review boards (IRBs) to approve pediatric research in 3 risk and benefit cat-e g o r i e s : ( 1 ) s t u d i e s t h a t o f f e r participating children a prospect of direct benefit 16 ; (2) studies that do not of-Context Federal regulations allow children in the United States to be enrolled in clinical research only when the institutional review board (IRB) determines that the risks are minimal or a minor increase over minimal, or that the research offers a prospect of direct benefit. Despite this reliance on IRBs, no data exist on how IRBs apply the risk and benefit categories for pediatric research.Objective To determine how IRB chairpersons apply the federal risk and benefit categories for pediatric research. Design, Setting, and Participants Telephone survey, conducted between May and August 2002 of 188 randomly selected chairpersons of IRBs in the Unites States. The survey consisted of 21 questions to assess the application of federal risk standards to research procedures, whether certain interventions offer a prospect of direct benefit to participating children, and the extent to which IRBs use the federal definition of minimal risk when categorizing the risks of research procedures in children. Main Outcome MeasuresResponses regarding categorization of the risk level and direct benefits of pediatric research procedures. ResultsA single blood draw was the only procedure categorized as minimal risk by a majority (152 or 81%) of the 188 respondents. An electromyogram was categorized as minimal or a minor increase over minimal risk by 100 (53%) and as more than a minor increase over minimal risk by 77 (41%). Allergy skin testing was categorized as minimal risk by 43 IRB chairpersons (23%), a minor increase over minimal risk by 81 (43%), and more than a minor increase over minimal risk by 51 (27%). Regarding benefits, 113 chairpersons (60%) considered ad...

High social value is fundamental to justifying these studies

The U.S. federal regulations require investigators conducting nonbeneficial research to obtain the assent of children who are capable of providing it. Unfortunately, there has been no analysis of which children are capable of assent or even what abilities ground the capacity to give assent. Why should investigators be required to obtain the positive agreement of some children, but not others, before enrolling them in research that does not offer a compensating potential for direct benefit? We argue that the scope of children's research decision making should be based on the principles of respect for autonomy and nonmaleficence. These principles imply that the threshold for assent should be fixed at 14 years of age, and a dissent requirement should be adopted for all children in the context of nonbeneficial research.

Vital organ transplantation is premised on 'the dead donor rule': donors must be declared dead according to medical and legal criteria prior to donation. However, it is controversial whether individuals diagnosed as 'brain dead' are really dead in accordance with the established biological conception of death-the irreversible cessation of the functioning of the organism as a whole. A basic understanding of brain death is also relevant for giving valid, informed consent to serve as an organ donor. There is therefore a need for reliable empirical data on public understanding of brain death and vital organ transplantation. We conducted a review of the empirical literature that identified 43 articles with approximately 18,603 study participants. These data demonstrate that participants generally do not understand three key issues: (1) uncontested biological facts about brain death, (2) the legal status of brain death and (3) that organs are procured from brain dead patients while their hearts are still beating and before their removal from ventilators. These data suggest that, despite scholarly claims of widespread public support for organ donation from brain dead patients, the existing data on public attitudes regarding brain death and organ transplantation reflect substantial public confusion. Our review raises questions about the validity of consent for vital organ transplantation and suggests that existing data are of little assistance in developing policy proposals for organ transplantation from brain dead patients. New approaches to rigorous empirical research with educational components and evaluations of understanding are urgently needed.

Contentious risks demand a new approach