Specifying a target trial prevents immortal time bias and other self-inflicted injuries in observational analyses

J Clin Epidemiol. 2016 Nov:79:70-75. doi: 10.1016/j.jclinepi.2016.04.014. Epub 2016 May 27.


Many analyses of observational data are attempts to emulate a target trial. The emulation of the target trial may fail when researchers deviate from simple principles that guide the design and analysis of randomized experiments. We review a framework to describe and prevent biases, including immortal time bias, that result from a failure to align start of follow-up, specification of eligibility, and treatment assignment. We review some analytic approaches to avoid these problems in comparative effectiveness or safety research.

Keywords: Comparative effectiveness research; Immortal time bias; Observational; Selection bias; Target trial; Time zero; studies.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Bias
  • Comparative Effectiveness Research / statistics & numerical data
  • Epidemiologic Research Design*
  • Humans
  • Observational Studies as Topic / statistics & numerical data*
  • Selection Bias
  • Time Factors