title: Bias due to secondary transmission in estimation of attributable risk from intervention trials.
abstract: BACKGROUND
  An important concept in epidemiology is attributable risk, defined as the difference in risk between an exposed and an unexposed group. For example, in an intervention trial, the attributable risk is the difference in risk between a group that receives an intervention and another that does not. A fundamental assumption in estimating the attributable risk associated with the intervention is that disease outcomes are independent. When estimating population risks associated with treatment regimens designed to affect exposure to infectious pathogens, however, there may be bias due to the fact that infectious pathogens can be transmitted from host to host causing a potential statistical dependency in disease status among participants.
  
  
  METHODS
  To estimate this bias, we used a mathematical model of community- and household-level disease transmission to explicitly incorporate the dependency among participants. We illustrate the method using a plausible model of infectious diarrheal disease.
  
  
  RESULTS
  Analysis of the model suggests that this bias in attributable risk estimates is a function of transmission from person to person, either directly or indirectly via the environment.
  
  
  CONCLUSIONS
  By incorporating these dependencies among individuals in a transmission model, we show how the bias of attributable risk estimates could be quantified to adjust effect estimates reported from intervention trials.
authors.affiliation: School of Public Health, University of California, Berkeley, CA 94720-7360, USA. eisenber@socrates.berkeley.edu
authors.forename: Joseph N S
authors.initials: JN
authors.lastname: Eisenberg
authors.forename: Bryan L
authors.initials: BL
authors.lastname: Lewis
authors.forename: Travis C
authors.initials: TC
authors.lastname: Porco
authors.forename: Alan H
authors.initials: AH
authors.lastname: Hubbard
authors.forename: John M
authors.initials: JM
authors.lastname: Colford
mesh_terms: D015982:Bias; D002986:Clinical Trials as Topic; D003141:Communicable Diseases / Q000453:epidemiology / Q000635:transmission*; D003967:Diarrhea / Q000453:epidemiology; D016021:Epidemiologic Studies; D006801:Humans; D008962:Models, Theoretical; D012107:Research Design; D018570:Risk Assessment