title: Potential Biases in Estimating Absolute and Relative Case-Fatality Risks during Outbreaks.
abstract: Estimating the case-fatality risk (CFR)-the probability that a person dies from an infection given that they are a case-is a high priority in epidemiologic investigation of newly emerging infectious diseases and sometimes in new outbreaks of known infectious diseases. The data available to estimate the overall CFR are often gathered for other purposes (e.g., surveillance) in challenging circumstances. We describe two forms of bias that may affect the estimation of the overall CFR-preferential ascertainment of severe cases and bias from reporting delays-and review solutions that have been proposed and implemented in past epidemics. Also of interest is the estimation of the causal impact of specific interventions (e.g., hospitalization, or hospitalization at a particular hospital) on survival, which can be estimated as a relative CFR for two or more groups. When observational data are used for this purpose, three more sources of bias may arise: confounding, survivorship bias, and selection due to preferential inclusion in surveillance datasets of those who are hospitalized and/or die. We illustrate these biases and caution against causal interpretation of differential CFR among those receiving different interventions in observational datasets. Again, we discuss ways to reduce these biases, particularly by estimating outcomes in smaller but more systematically defined cohorts ascertained before the onset of symptoms, such as those identified by forward contact tracing. Finally, we discuss the circumstances in which these biases may affect non-causal interpretation of risk factors for death among cases.
authors.affiliation: Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America; MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
authors.forename: Marc
authors.initials: M
authors.lastname: Lipsitch
authors.affiliation: MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
authors.forename: Christl A
authors.initials: CA
authors.lastname: Donnelly
authors.affiliation: MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
authors.forename: Christophe
authors.initials: C
authors.lastname: Fraser
authors.affiliation: MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
authors.forename: Isobel M
authors.initials: IM
authors.lastname: Blake
authors.affiliation: MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
authors.forename: Anne
authors.initials: A
authors.lastname: Cori
authors.affiliation: MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Dorigatti
authors.affiliation: MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
authors.forename: Neil M
authors.initials: NM
authors.lastname: Ferguson
authors.affiliation: MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
authors.forename: Tini
authors.initials: T
authors.lastname: Garske
authors.affiliation: MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
authors.forename: Harriet L
authors.initials: HL
authors.lastname: Mills
authors.affiliation: MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
authors.forename: Steven
authors.initials: S
authors.lastname: Riley
authors.affiliation: MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom; Centre for Global Health, Institut Pasteur, Paris, France.
authors.forename: Maria D
authors.initials: MD
authors.lastname: Van Kerkhove
authors.affiliation: Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Hernán
mesh_terms: D015982:Bias; D003141:Communicable Diseases / Q000453:epidemiology* / Q000401:mortality*; D003627:Data Interpretation, Statistical; D004196:Disease Outbreaks / Q000706:statistics & numerical data*; D006801:Humans; D012307:Risk Factors