title: Comparative Effectiveness Research Using Observational Data: Active Comparators to Emulate Target Trials with Inactive Comparators.
abstract: BACKGROUND
  Because a comparison of noninitiators and initiators of treatment may be hopelessly confounded, guidelines for the conduct of observational research often recommend using an "active" comparator group consisting of people who initiate a treatment other than the medication of interest. In this paper, we discuss the conditions under which this approach is valid if the goal is to emulate a trial with an inactive comparator.
  We provide conditions under which a target trial in a subpopulation can be validly emulated from observational data, using an active comparator that is known or believed to be inactive for the outcome of interest. The average treatment effect in the population as a whole is not identified, but under certain conditions this approach can be used to emulate a trial in the subset of individuals who were treated with the treatment of interest, in the subset of individuals who were treated with the treatment of interest but not with the comparator, or in the subset of individuals who were treated with both the treatment of interest and the active comparator.
  We discuss whether the required conditions can be expected to hold in pharmacoepidemiologic research, with a particular focus on whether the conditions are plausible in situations where the standard analysis fails due to unmeasured confounding by access to health care or health seeking behaviors.
  
  
  CONCLUSIONS
  The conditions discussed in this paper may at best be approximately true. Investigators using active comparator designs to emulate trials with inactive comparators should exercise caution.
authors.affiliation: Harvard TH Chan School of Public Health.
authors.forename: Anders
authors.initials: A
authors.lastname: Huitfeldt
authors.affiliation: Harvard University.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Hernan
authors.affiliation: University of Oslo.
authors.forename: Mette
authors.initials: M
authors.lastname: Kalager
authors.affiliation: Harvard TH Chan School of Public Health.
authors.forename: James M
authors.initials: JM
authors.lastname: Robins
keywords: Comparative Effectiveness Research (CER); Electronic Medical Record (EMR); Evidence Based Medicine; Methods