title: Study sensitivity: Evaluating the ability to detect effects in systematic reviews of chemical exposures.
abstract: A critical step in systematic reviews of potential health hazards is the structured evaluation of the strengths and weaknesses of the included studies; risk of bias is a term often used to represent this process, specifically with respect to the evaluation of systematic errors that can lead to inaccurate (biased) results (i.e. focusing on internal validity). Systematic review methods developed in the clinical medicine arena have been adapted for use in evaluating environmental health hazards; this expansion raises questions about the scope of risk of bias tools and the extent to which they capture the elements that can affect the interpretation of results from environmental and occupational epidemiology studies and in vivo animal toxicology studies, (the studies typically available for assessment of risk of chemicals). One such element, described here as "sensitivity", is a measure of the ability of a study to detect a true effect or hazard. This concept is similar to the concept of the sensitivity of an assay; an insensitive study may fail to show a difference that truly exists, leading to a false conclusion of no effect. Factors relating to study sensitivity should be evaluated in a systematic manner with the same rigor as the evaluation of other elements within a risk of bias framework. We discuss the importance of this component for the interpretation of individual studies, examine approaches proposed or in use to address it, and describe how it relates to other evaluation components. The evaluation domains contained within a risk of bias tool can include, or can be modified to include, some features relating to study sensitivity; the explicit inclusion of these sensitivity criteria with the same rigor and at the same stage of study evaluation as other bias-related criteria can improve the evaluation process. In some cases, these and other features may be better addressed through a separate sensitivity domain. The combined evaluation of risk of bias and sensitivity can be used to identify the most informative studies, to evaluate the confidence of the findings from individual studies and to identify those study elements that may help to explain heterogeneity across the body of literature.
authors.affiliation: National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC, USA. Electronic address: cooper.glinda@epa.gov.
authors.forename: Glinda S
authors.initials: GS
authors.lastname: Cooper
authors.affiliation: Office of the Report on Carcinogens, Division of the National Toxicology Program, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Research Triangle Park, NC, USA.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Lunn
authors.affiliation: Department of Environmental Science and Analytical Chemistry (ACES), Stockholm University, 106 91 Stockholm, Sweden.
authors.forename: Marlene
authors.initials: M
authors.lastname: Ågerstrand
authors.affiliation: National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC, USA.
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Glenn
authors.affiliation: National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Kraft
authors.affiliation: National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC, USA.
authors.forename: April M
authors.initials: AM
authors.lastname: Luke
authors.affiliation: Integrated Laboratory Systems (ILS), Research Triangle Park, NC, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Ratcliffe
mesh_terms: D000818:Animals; D015982:Bias; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000633:toxicity*; D006801:Humans; D017594:Publication Bias; D012196:Review Literature as Topic
chemical_list: D004785:Environmental Pollutants
keywords: Bias; Chemical hazard assessment; Environmental health; Study sensitivity; Systematic review; Validity