title: The Role of Ultrasound Compared to Biopsy of Temporal Arteries in the Diagnosis and Treatment of Giant Cell Arteritis (TABUL): a diagnostic accuracy and cost-effectiveness study.
abstract: Giant cell arteritis (GCA) is a relatively common form of primary systemic vasculitis, which, if left untreated, can lead to permanent sight loss. We compared ultrasound as an alternative diagnostic test with temporal artery biopsy, which may be negative in 9-61% of true cases.
  
  
  
  To compare the clinical effectiveness and cost-effectiveness of ultrasound with biopsy in diagnosing patients with suspected GCA.
  
  
  
  Prospective multicentre cohort study.
  
  
  
  Secondary care.
  
  
  
  A total of 381 patients referred with newly suspected GCA.
  
  
  
  Sensitivity, specificity and cost-effectiveness of ultrasound compared with biopsy or ultrasound combined with biopsy for diagnosing GCA and interobserver reliability in interpreting scan or biopsy findings.
  
  
  
  We developed and implemented an ultrasound training programme for diagnosing suspected GCA. We recruited 430 patients with suspected GCA. We analysed 381 patients who underwent both ultrasound and biopsy within 10 days of starting treatment for suspected GCA and who attended a follow-up assessment (median age 71.1 years; 72% female). The sensitivity of biopsy was 39% [95% confidence interval (CI) 33% to 46%], which was significantly lower than previously reported and inferior to ultrasound (54%, 95% CI 48% to 60%); the specificity of biopsy (100%, 95% CI 97% to 100%) was superior to ultrasound (81%, 95% CI 73% to 88%). If we scanned all suspected patients and performed biopsies only on negative cases, sensitivity increased to 65% and specificity was maintained at 81%, reducing the need for biopsies by 43%. Strategies combining clinical judgement (clinician's assessment at 2 weeks) with the tests showed sensitivity and specificity of 91% and 81%, respectively, for biopsy and 93% and 77%, respectively, for ultrasound; cost-effectiveness (incremental net monetary benefit) was £485 per patient in favour of ultrasound with both cost savings and a small health gain. Inter-rater analysis revealed moderate agreement among sonographers (intraclass correlation coefficient 0.61, 95% CI 0.48 to 0.75), similar to pathologists (0.62, 95% CI 0.49 to 0.76).
  
  
  
  There is no independent gold standard diagnosis for GCA. The reference diagnosis used to determine accuracy was based on classification criteria for GCA that include clinical features at presentation and biopsy results.
  
  
  
  We have demonstrated the feasibility of providing training in ultrasound for the diagnosis of GCA. Our results indicate better sensitivity but poorer specificity of ultrasound compared with biopsy and suggest some scope for reducing the role of biopsy. The moderate interobserver agreement for both ultrasound and biopsy indicates scope for improving assessment and reporting of test results and challenges the assumption that a positive biopsy always represents GCA.
  
  
  
  Further research should address the issue of an independent reference diagnosis, standards for interpreting and reporting test results and the evaluation of ultrasound training, and should also explore the acceptability of these new diagnostic strategies in GCA.
  
  
  
  The National Institute for Health Research Health Technology Assessment programme.
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
authors.forename: Raashid
authors.initials: R
authors.lastname: Luqmani
authors.affiliation: School of Health and Related Research, University of Sheffield, Sheffield, UK.
authors.forename: Ellen
authors.initials: E
authors.lastname: Lee
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
authors.forename: Surjeet
authors.initials: S
authors.lastname: Singh
authors.affiliation: School of Health and Related Research, University of Sheffield, Sheffield, UK.
authors.forename: Mike
authors.initials: M
authors.lastname: Gillett
authors.affiliation: Immanuel Krankenhaus Berlin, Medical Centre for Rheumatology Berlin-Buch, Berlin, Germany.
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Schmidt
authors.affiliation: School of Health and Related Research, University of Sheffield, Sheffield, UK.
authors.forename: Mike
authors.initials: M
authors.lastname: Bradburn
authors.affiliation: Department of Rheumatology, Southend University Hospital NHS Foundation Trust, Southend, UK.
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Dasgupta
authors.affiliation: Department of Rheumatology, Hospital of Southern Norway, Kristiansand, Norway.
authors.forename: Andreas P
authors.initials: AP
authors.lastname: Diamantopoulos
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
authors.forename: Wulf
authors.initials: W
authors.lastname: Forrester-Barker
authors.affiliation: Primary Care Diagnostics, University of Exeter Medical School, Exeter, UK.
authors.forename: William
authors.initials: W
authors.lastname: Hamilton
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
authors.forename: Shauna
authors.initials: S
authors.lastname: Masters
authors.affiliation: Department of Neuropathology and Ocular Pathology, Oxford University Hospitals NHS Trust, Oxford, UK.
authors.forename: Brendan
authors.initials: B
authors.lastname: McDonald
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
authors.forename: Eugene
authors.initials: E
authors.lastname: McNally
authors.affiliation: Department of Rheumatology, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors.forename: Colin
authors.initials: C
authors.lastname: Pease
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Piper
authors.affiliation: Oxford Eye Hospital, Oxford University Hospitals NHS Trust, Oxford, UK.
authors.forename: John
authors.initials: J
authors.lastname: Salmon
authors.affiliation: School of Health and Related Research, University of Sheffield, Sheffield, UK.
authors.forename: Allan
authors.initials: A
authors.lastname: Wailoo
authors.affiliation: Department of Pathology, Southend University Hospital NHS Foundation Trust, Southend, UK.
authors.forename: Konrad
authors.initials: K
authors.lastname: Wolfe
authors.affiliation: Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Hutchings
mesh_terms: D000368:Aged; D001706:Biopsy / Q000191:economics* / Q000379:methods / Q000592:standards; D003362:Cost-Benefit Analysis; D005260:Female; D013700:Giant Cell Arteritis / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000188:drug therapy; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013699:Temporal Arteries / Q000000981:diagnostic imaging*; D014463:Ultrasonography / Q000191:economics* / Q000379:methods / Q000592:standards
chemical_list: D005938:Glucocorticoids