title: Evaluating the risks of clinical research: direct comparative analysis.
abstract: OBJECTIVE
  Many guidelines and regulations allow children and adolescents to be enrolled in research without the prospect of clinical benefit when it poses minimal risk. However, few systematic methods exist to determine when research risks are minimal. This situation has led to significant variation in minimal risk judgments, raising concern that some children are not being adequately protected. To address this concern, we describe a new method for implementing the widely endorsed "risks of daily life" standard for minimal risk. This standard defines research risks as minimal when they do not exceed the risks posed by daily life activities or routine examinations.
  
  
  METHODS
  This study employed a conceptual and normative analysis, and use of an illustrative example.
  
  
  RESULTS
  Different risks are composed of the same basic elements: Type, likelihood, and magnitude of harm. Hence, one can compare the risks of research and the risks of daily life by comparing the respective basic elements with each other. We use this insight to develop a systematic method, direct comparative analysis, for implementing the "risks of daily life" standard for minimal risk. The method offers a way of evaluating research procedures that pose the same types of risk as daily life activities, such as the risk of experiencing anxiety, stress, or other psychological harm. We thus illustrate how direct comparative analysis can be applied in practice by using it to evaluate whether the anxiety induced by a respiratory CO2 challenge poses minimal or greater than minimal risks in children and adolescents.
  
  
  CONCLUSIONS
  Direct comparative analysis is a systematic method for applying the "risks of daily life" standard for minimal risk to research procedures that pose the same types of risk as daily life activities. It thereby offers a method to protect children and adolescents in research, while ensuring that important studies are not blocked because of unwarranted concerns about research risks.
authors.affiliation: 1 Department of Social Science, Health & Medicine, King's College London , United Kingdom .
authors.forename: Annette
authors.initials: A
authors.lastname: Rid
authors.forename: Emily
authors.initials: E
authors.lastname: Abdoler
authors.forename: Roxann
authors.initials: R
authors.lastname: Roberson-Nay
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Pine
authors.forename: David
authors.initials: D
authors.lastname: Wendler
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D001007:Anxiety / Q000139:chemically induced; D002245:Carbon Dioxide / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic / Q000009:adverse effects* / Q000941:ethics / Q000592:standards*; D006801:Humans; D016584:Panic Disorder / Q000139:chemically induced; D018570:Risk Assessment / Q000379:methods*; D055815:Young Adult
chemical_list: D002245:Carbon Dioxide