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Byline: Robert D. Truog (1,2) Abstract: Specific regulations regarding oversight of research in children vary from country to country, but most share common principles derived from major consensus documents. Whereas the permissibility of research on adults depends heavily upon the informed consent of the subject, the regulation of research in pediatrics is focused primarily upon protection of the subjects from research risks. Since patients who require intensive care are commonly at high risk for complications related to the severity of their illnesses, justifying the risks of research on critically ill children may therefore be particularly challenging. Use of an approach known as 'component analysis' can be very helpful in separating the risks attributable to the medical care itself from those that should be ascribed to the research. After identifying and isolating the research interventions, a three-step approach is helpful for evaluating the 'net risks' of the research: (1) Separate each component of the research into discrete interventions. (2) Any intervention for which the benefits equal or exceed the risks is ethically justified. (3) For interventions in which the risks exceed the benefits, the 'net risk' for each intervention needs to be justified, as follows: (a) the interventions may not exceed the locally defined threshold for pediatric research (e.a-g., not greater than a minor increment more than minimal risk, as in the U.S. regulations) and (b) the scientific value of the study for improving the care of future children must be sufficient to justify the sum of the net risks of the research interventions. Author Affiliation: (1) Department of Social Medicine, Harvard Medical School, 651 Huntington Avenue, 02115, Boston, MA, USA (2) Department of Critical Care Medicine, Children's Hospital, Bader 6, 300 Longwood Avenue, 02115, Boston, MA, USA Article History: Registration Date: 05/10/2007 Received Date: 19/08/2007 Accepted Date: 30/09/2007 Online Date: 03/11/2007

Objective. To assess how Institutional Review Boards (IRBs) implement the assent requirement for research with children. Methods. Telephone interviews were conducted with 188 chairpersons of IRBs from a range of institutions nationwide. Respondents were queried on 4 topics: 1) which children are considered capable of assent, 2) which information investigators must provide pediatric research subjects, 3) whether IRBs favor the enrollment of children who are capable of assent, and 4) how chairpersons view payment for children's research participation. Results. Half of IRBs have a method that they require investigators to follow when determining which children are capable of assent, most commonly an age cutoff. Half of IRBs do not have a method, and the majority rely on investigators' clinical judgment. IRBs largely follow the adult research regulations when determining which information should be provided to an assenting child. A total of 58% of IRBs would enroll a child who is incapable of assent in a nonbeneficial study, even if children who are capable of assent could be enrolled instead. Almost half (46%) of chairpersons believe that it sometimes or always acceptable to offer incentive payments to children, and more than one third (35%) thought it acceptable to offer payment to the parents. Conclusion. When possible, IRBs follow the federal regulations for research with adults when implementing the assent requirement. For considerations that do not have analogs in the adult regulations, IRB practices vary widely. These data suggest that IRBs need guidance on how to implement the assent requirement in a way that provides appropriate protections for pediatric research subjects. Pediatrics 2004;113:1747-1752; child, IRB., ABBREVIATIONS. IRB, Institutional Review Board; OR, odds ratio. Enrolling children in clinical research raises special ethical concerns because they lack the legal standing to consent and often the capacity to [...]

The US Federal Code limits research with healthy children to no more than a minimal risk of harm; it restricts research with children who have some disorder or condition to no more than a minor increase over minimal risk, unless potential harms are offset by potential benefits to them, as in therapeutic studies. Higher risk studies require "407 approval," named after the relevant section of the code describing requirements. Rarely used until recently, 407 approval requirements include Institutional Review Board approval and authorization by the Secretary of the Department of Health and Human Services after consultation with a panel of experts; a period for public comment; and assurances that there are adequate permission, consent, and assent. This 407-approval mechanism contains both procedural and interpretative ambiguities, which raise ethical concerns about 1) the expertise represented on advisory panels, 2) the scope of the information offered to the public for comment and its potential conflicts with investigators' intellectual property or commercial interests, 3) whether any upper level of risk exists, and 4) how it conforms with other policies such as the best interest of the child standard in the law or in medical decision making. Pediatrics 2004;113:1783-1789; children, ethics, experimentation, health policy, human subjects, IRBs, law, pediatrics, research., ABBREVIATIONS. IRB, Institutional Review Board; DHHS, Department of Health and Human Services; CFR, Code of Federal Regulations; OHRP, Office for Human Research Protections; NIH, National Institutes of Health; HIV, human [...]

The policymakers and researchers are struggling to find ways to access the benefits of pediatric research protecting the participants from excessive risks. Protection and safeguards that go well beyond obtaining informed consent from parents is required for performing pediatric research.