title: Quantifying the federal minimal risk standard: implications for pediatric research without a prospect of direct benefit.
abstract: United States federal regulations allow institutional review boards (IRBs) to approve pediatric research that does not offer participants a "prospect of direct" benefit only when the risks are minimal or a "minor" increase over minimal. The federal regulations define minimal risks based on the risks "ordinarily encountered in daily life or during routine physical or psychological examinations or tests." In the absence of empirical data, IRB members may assume they are familiar with the risks of daily life and with the risks of routine examinations and tests and rely on their own intuitive judgment to make these assessments. Yet intuitive judgment of risk is subject to systematic errors, highlighting the need for empirical data to guide IRB review and approval of pediatric research. Current data reveal that car trips pose the highest risk of mortality ordinarily encountered by healthy children. On average, these risks are approximately 0.06 per million for children aged 14 years and younger, and approximately 0.4 per million for children aged 15 through 19 years. Riskier, but still ordinary, car trips pose an approximately 0.6 per million chance of death for children aged 14 years and younger and an approximately 4 per million chance of death for children aged 15 through 19 years. Participation in sports represents the upper end of the range of morbidity risks for healthy children. For every million instances of playing basketball, approximately 1900 individuals will sustain injuries, including 180 broken bones and 58 permanent disabilities. These findings suggest IRBs are implementing the federal minimal risk standard too cautiously in many cases. These data also raise the question of whether the federal minimal risk standard may sometimes fail to provide sufficient protection for children, prompting the need to consider alternative standards.
authors.affiliation: Department of Clinical Bioethics, NIH Clinical Center, National Institutes of Health, Bethesda, Md 20892, USA. dwendler@nih.gov
authors.forename: David
authors.initials: D
authors.lastname: Wendler
authors.forename: Leah
authors.initials: L
authors.lastname: Belsky
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Thompson
authors.forename: Ezekiel J
authors.initials: EJ
authors.lastname: Emanuel
mesh_terms: D000203:Activities of Daily Living; D000293:Adolescent; D002648:Child; D002986:Clinical Trials as Topic / Q000941:ethics* / Q000331:legislation & jurisprudence* / Q000592:standards; D028744:Ethics Committees, Research; D035082:Federal Government; D033161:Government Regulation; D017408:Guidelines as Topic; D006801:Humans; D033281:Nontherapeutic Human Experimentation / Q000941:ethics* / Q000331:legislation & jurisprudence* / Q000592:standards; D018579:Patient Selection; D010372:Pediatrics / Q000941:ethics* / Q000331:legislation & jurisprudence* / Q000592:standards; D011640:Public Policy; D018570:Risk Assessment / Q000706:statistics & numerical data*; D014481:United States