Correcting for bias in the selection and validation of informative diagnostic tests
Author(s)
Robertson, David S
Prevost, A Toby
Bowden, Jack
Type
Journal Article
Abstract
When developing a new diagnostic test for a disease, there are often multiple candidate classifiers to choose from, and it is unclear if any will offer an improvement in performance compared with current technology. A two‐stage design can be used to select a promising classifier (if one exists) in stage one for definitive validation in stage two. However, estimating the true properties of the chosen classifier is complicated by the first stage selection rules. In particular, the usual maximum likelihood estimator (MLE) that combines data from both stages will be biased high. Consequently, confidence intervals and p‐values flowing from the MLE will also be incorrect. Building on the results of Pepe et al. (SIM 28:762–779), we derive the most efficient conditionally unbiased estimator and exact confidence intervals for a classifier's sensitivity in a two‐stage design with arbitrary selection rules; the condition being that the trial proceeds to the validation stage. We apply our estimation strategy to data from a recent family history screening tool validation study by Walter et al. (BJGP 63:393–400) and are able to identify and successfully adjust for bias in the tool's estimated sensitivity to detect those at higher risk of breast cancer.
Date Issued
2015-03-10
Date Acceptance
2014-12-17
Citation
Statistics in Medicine, 2015, 34 (8), pp.1417-1437
ISSN
0277-6715
Publisher
Wiley
Start Page
1417
End Page
1437
Journal / Book Title
Statistics in Medicine
Volume
34
Issue
8
Copyright Statement
© 2015 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
This is an open access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000351207000011&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Physical Sciences
Mathematical & Computational Biology
Public, Environmental & Occupational Health
Medical Informatics
Medicine, Research & Experimental
Statistics & Probability
Research & Experimental Medicine
Mathematics
diagnostic tests
group sequential design
family history
uniformly minimum variance unbiased estimator
UNBIASED ESTIMATION
EARLY TERMINATION
CLINICAL-TRIALS
CONDITIONAL ESTIMATION
SEQUENTIAL DESIGNS
2-STAGE
CANCER
BIOMARKER
FUTILITY
Publication Status
Published
Date Publish Online
2015-02-01