Christiana A. Naaktgeboren, MPH; Joris A.H. de Groot, PhD; Maarten van Smeden, MSc; Karel G.M. Moons, PhD; Johannes B. Reitsma, MD, PhD
Financial Support: By the Netherlands Organization for Scientific Research (project 918.10.615).
Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-0322.
Requests for Single Reprints: Christiana A. Naaktgeboren, MPH, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, the Netherlands.
Current Author Addresses: Ms. Naaktgeboren; Drs. de Groot, Moons, and Reitsma; and Mr. van Smeden: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, the Netherlands.
Author Contributions: Conception and design: C.A. Naaktgeboren, J.A.H. de Groot, M. van Smeden, K.G.M. Moons, J.B. Reitsma.
Analysis and interpretation of the data: K.G.M. Moons, J.B. Reitsma.
Drafting of the article: C.A. Naaktgeboren, J.A.H. de Groot, K.G.M. Moons.
Critical revision of the article for important intellectual content: C.A. Naaktgeboren, J.A.H. de Groot, M. van Smeden, K.G.M. Moons, J.B. Reitsma.
Final approval of the article: J.A.H. de Groot, M. van Smeden, K.G.M. Moons, J.B. Reitsma.
Statistical expertise: J.A.H. de Groot, M. van Smeden, K.G.M. Moons, J.B. Reitsma.
Obtaining of funding: K.G.M. Moons.
Administrative, technical, or logistic support: J.A.H. de Groot.
Collection and assembly of data: K.G.M. Moons.
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.
Naaktgeboren CA, de Groot JA, van Smeden M, Moons KG, Reitsma JB. Evaluating Diagnostic Accuracy in the Face of Multiple Reference Standards. Ann Intern Med. ;159:195–202. doi: 10.7326/0003-4819-159-3-201308060-00009
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Published: Ann Intern Med. 2013;159(3):195-202.
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