title: Modeling Canadian Quality Control Test Program for Steroid Hormone Receptors in Breast Cancer: Diagnostic Accuracy Study.
abstract: The Canadian Immunohistochemistry Quality Control program monitors clinical laboratory performance for estrogen receptor and progesterone receptor tests used in breast cancer treatment management in Canada. Current methods assess sensitivity and specificity at each time point, compared with a reference standard. We investigate alternative performance analysis methods to enhance the quality assessment. We used 3 methods of analysis: meta-analysis of sensitivity and specificity of each laboratory across all time points; sensitivity and specificity at each time point for each laboratory; and fitting models for repeated measurements to examine differences between laboratories adjusted by test and time point. Results show 88 laboratories participated in quality control at up to 13 time points using typically 37 to 54 histology samples. In meta-analysis across all time points no laboratories have sensitivity or specificity below 80%. Current methods, presenting sensitivity and specificity separately for each run, result in wide 95% confidence intervals, typically spanning 15% to 30%. Models of a single diagnostic outcome demonstrated that 82% to 100% of laboratories had no difference to reference standard for estrogen receptor and 75% to 100% for progesterone receptor, with the exception of 1 progesterone receptor run. Laboratories with significant differences to reference standard identified with Generalized Estimating Equation modeling also have reduced performance by meta-analysis across all time points. The Canadian Immunohistochemistry Quality Control program has a good design, and with this modeling approach has sufficient precision to measure performance at each time point and allow laboratories with a significantly lower performance to be targeted for advice.
authors.affiliation: *Department of Statistics and OR III, Complutense University of Madrid, Madrid, Spain †Department of Pathology and Laboratory Medicine, University of British Columbia ‡Canadian Immunohistochemistry Quality Control (CIQC) and Canadian Association of Pathologists §Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada ∥School of Health and Population Sciences, University of Birmingham, Birmingham, West Midlands, UK.
authors.forename: Teresa
authors.initials: T
authors.lastname: Pérez
authors.forename: Nikita
authors.initials: N
authors.lastname: Makrestsov
authors.forename: John
authors.initials: J
authors.lastname: Garatt
authors.forename: Emina
authors.initials: E
authors.lastname: Torlakovic
authors.forename: C Blake
authors.initials: CB
authors.lastname: Gilks
authors.forename: Susan
authors.initials: S
authors.lastname: Mallett
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D002170:Canada; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007753:Laboratories / Q000458:organization & administration; D017146:Models, Organizational; D011786:Quality Control; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D011960:Receptors, Estrogen; D011980:Receptors, Progesterone