title: A Randomized Study Comparing Digital Imaging to Traditional Glass Slide Microscopy for Breast Biopsy and Cancer Diagnosis.
abstract: BACKGROUND
  Digital whole slide imaging may be useful for obtaining second opinions and is used in many countries. However, the U.S. Food and Drug Administration requires verification studies.
  
  
  METHODS
  Pathologists were randomized to interpret one of four sets of breast biopsy cases during two phases, separated by ≥9 months, using glass slides or digital format (sixty cases per set, one slide per case,n= 240 cases). Accuracy was assessed by comparing interpretations to a consensus reference standard. Intraobserver reproducibility was assessed by comparing the agreement of interpretations on the same cases between two phases. Estimated probabilities of confirmation by a reference panel (i.e., predictive values) were obtained by incorporating data on the population prevalence of diagnoses.
  
  
  RESULTS
  Sixty-five percent of responding pathologists were eligible, and 252 consented to randomization; 208 completed Phase I (115 glass, 93 digital); and 172 completed Phase II (86 glass, 86 digital). Accuracy was slightly higher using glass compared to digital format and varied by category: invasive carcinoma, 96% versus 93% (P= 0.04); ductal carcinomain situ(DCIS), 84% versus 79% (P< 0.01); atypia, 48% versus 43% (P= 0.08); and benign without atypia, 87% versus 82% (P< 0.01). There was a small decrease in intraobserver agreement when the format changed compared to when glass slides were used in both phases (P= 0.08). Predictive values for confirmation by a reference panel using glass versus digital were: invasive carcinoma, 98% and 97% (not significant [NS]); DCIS, 70% and 57% (P= 0.007); atypia, 38% and 28% (P= 0.002); and benign without atypia, 97% and 96% (NS).
  
  
  CONCLUSIONS
  In this large randomized study, digital format interpretations were similar to glass slide interpretations of benign and invasive cancer cases. However, cases in the middle of the spectrum, where more inherent variability exists, may be more problematic in digital format. Future studies evaluating the effect these findings exert on clinical practice and patient outcomes are required.
authors.affiliation: Department of Medicine, University of Washington School of Medicine, Seattle, WA 98104, USA.
authors.forename: Joann G
authors.initials: JG
authors.lastname: Elmore
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Gary M
authors.initials: GM
authors.lastname: Longton
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Biostatistics, University of Washington School of Public Health, Seattle, WA 98104, USA.
authors.forename: Margaret S
authors.initials: MS
authors.lastname: Pepe
authors.affiliation: Department of Family Medicine, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Carney
authors.affiliation: Department of Medical Informatics and Clinical Epidemiology, Oregon Health and Science University, Portland, OR 97239, USA; Providence Cancer Center, Providence Health and Services Oregon, Portland, OR 97213, USA.
authors.forename: Heidi D
authors.initials: HD
authors.lastname: Nelson
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Kimberly H
authors.initials: KH
authors.lastname: Allison
authors.affiliation: Department of Family Medicine, University of Vermont, Burlington, VT 05405, USA.
authors.forename: Berta M
authors.initials: BM
authors.lastname: Geller
authors.affiliation: Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA.
authors.forename: Tracy
authors.initials: T
authors.lastname: Onega
authors.affiliation: The Dartmouth Institute for Health Policy and Clinical Practice, Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA.
authors.forename: Anna N A
authors.initials: AN
authors.lastname: Tosteson
authors.affiliation: Department of Computer Science and Engineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: Ezgi
authors.initials: E
authors.lastname: Mercan
authors.affiliation: Department of Computer Science and Engineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: Linda G
authors.initials: LG
authors.lastname: Shapiro
authors.affiliation: Department of Psychology, Tufts University, Medford, MA 02155, USA.
authors.forename: Tad T
authors.initials: TT
authors.lastname: Brunyé
authors.affiliation: Department of Medicine, University of Washington School of Medicine, Seattle, WA 98104, USA.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Morgan
authors.affiliation: Department of Pathology, UVM Cancer Center, University of Vermont, Burlington, VT 05405, USA.
authors.forename: Donald L
authors.initials: DL
authors.lastname: Weaver
keywords: Breast cancer; diagnostic accuracy; digital whole-slide imaging; intraobserver reproducibility