Evaluating diagnostic accuracy in the face of multiple reference standards

Ann Intern Med. 2013 Aug 6;159(3):195-202. doi: 10.7326/0003-4819-159-3-201308060-00009.


A universal challenge in studies that quantify the accuracy of diagnostic tests is establishing whether each participant has the disease of interest. Ideally, the same preferred reference standard would be used for all participants; however, for practical or ethical reasons, alternative reference standards that are often less accurate are frequently used instead. The use of different reference standards across participants in a single study is known as differential verification.Differential verification can cause severely biased accuracy estimates of the test or model being studied. Many variations of differential verification exist, but not all introduce the same risk of bias. A risk-of-bias assessment requires detailed information about which participants receive which reference standards and an estimate of the accuracy of the alternative reference standard. This article classifies types of differential verification and explores how they can lead to bias. It also provides guidance on how to report results and assess the risk of bias when differential verification occurs and highlights potential ways to correct for the bias.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bias
  • Diagnostic Tests, Routine / standards*
  • Humans
  • Reference Standards
  • Risk Assessment