Interferon-gamma release assays for diagnostic evaluation of active tuberculosis (IDEA): test accuracy study and economic evaluation Takwoingi, Yemisi; Partlett, Christopher; Deeks, Jonathan
License: None: All rights reserved Document Version Peer reviewed version Citation for published version (Harvard): Takwoingi, Y, Partlett, C & Deeks, J 2016, 'Interferon-gamma release assays for diagnostic evaluation of active tuberculosis (IDEA): test accuracy study and economic evaluation' Health Technology Assessment.
Link to publication on Research at Birmingham portal
Publisher Rights Statement: Final Version of Record to appear at: https://www.journalslibrary.nihr.ac.uk/hta/ Checked 6/1/2017
General rights Unless a licence is specified above, all rights (including copyright and moral rights) in this document are retained by the authors and/or the copyright holders. The express permission of the copyright holder must be obtained for any use of this material other than for purposes permitted by law. •Users may freely distribute the URL that is used to identify this publication. •Users may download and/or print one copy of the publication from the University of Birmingham research portal for the purpose of private study or non-commercial research. •User may use extracts from the document in line with the concept of ‘fair dealing’ under the Copyright, Designs and Patents Act 1988 (?) •Users may not further distribute the material nor use it for the purposes of commercial gain. Where a licence is displayed above, please note the terms and conditions of the licence govern your use of this document. When citing, please reference the published version. Take down policy While the University of Birmingham exercises care and attention in making items available there are rare occasions when an item has been uploaded in error or has been deemed to be commercially or otherwise sensitive. If you believe that this is the case for this document, please contact
[email protected] providing details and we will remove access to the work immediately and investigate.
Download date: 15. Aug. 2018
Interferon-gamma release assays for diagnostic evaluation of active tuberculosis (IDEA): test accuracy study and economic evaluation Yemisi Takwoingi,1 Hilary Whitworth,2 Melanie Rees-Roberts,2,3 Amarjit Badhan,2,3 Christopher Partlett,1 Nathan Green,4,5,6,7 Aime Boakye,2 Heather Lambie,2 Luigi Marongiu,2 Mark Jit,7,8 Peter White,4,5,6,7 Jonathan Deeks,1 Onn Min Kon,2,3,9 and Ajit Lalvani2,3* on behalf of the IGRAs for Diagnostic Evaluation of Active TB (IDEA) Study Group
Affiliations 1
Institute of Applied Health Research, University of Birmingham, Birmingham, UK
2
Tuberculosis Research Centre, National Heart and Lung Institute, Imperial College, London,
3
NIHR Health Protection Research Unit in Respiratory Infections, Imperial College London,
4
NIHR Health Protection Research Unit in Modelling Methodology, Imperial College
London 5
MRC Centre for Outbreak Analysis and Modelling, Imperial College London
6
Department of Infectious Disease Epidemiology, Imperial College London
7
Modelling and Economics Unit, Centre for Infectious Disease Surveillance and Control,
Public Health England 8
Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical
Medicine, London 9
St Mary’s Hospital, Imperial College Healthcare Trust, London, UK
*Corresponding author
[email protected]
IDEA study collaborators: D Abdoyeku, H Branley, F Chua, C Conlon, G Cooke, R Davison, M Dedicoat, H Kunst, M Lipman, M Loebingher, W Lynn, D Macallan, S Menzies, N Nathani, R O’ Connell, F Post, A Pozniak, M Wiselka, G Woltmann.
Competing interests of authors: Professor Ajit Lalvani is named inventor for several patents underpinning T cell-based diagnosis including IFN-gamma ELISpot, ESAT-6, CFP10, Rv3615c, Rv3873 and Rv3879c. He has royalty entitlements from the University of
Oxford spin-out company (Oxford Immunotec plc), in which he has held a minority share of equity. A Lalvani is a member of the EME Board. Professor Jonathan Deeks is a member of the HTA Commissioning Board and the HTA Efficient Study Designs Board. Professor Onn Min Kon is Chair of the UK Joint Tuberculosis Committee. Dr Peter White has received research funding from Otsuka SA for a retrospective study of multidrug-resistant tuberculosis treatment in several eastern European countries. All other authors report no potential conflicts.
Keywords: sensitivity; specificity; diagnosis; tuberculosis; T-SPOT.TB; QuantiFERON GOLD In Tube; interferon-gamma; ESAT-6; CFP-10; ELISpot; Rv3615c; Rv2654; Rv3879c; Rv3873.
Word count: 46,337 (including title page, tables, legends and all sections)
Abstract Background: Interferon-gamma release assays (IGRAs) are blood tests recommended for diagnosis of tuberculosis (TB) infection. There is currently uncertainty in the role and clinical utility of IGRAs in the diagnostic work up of suspected active TB in routine NHS clinical practice.
Objectives: To compare the diagnostic accuracy and cost-effectiveness of T-SPOT.TB and QuantiFERON GOLD In-Tube (QFT-GIT) for diagnosis of suspected active TB; and to estimate the diagnostic accuracy of next generation IGRAs.
Design: Prospective within-patient comparative diagnostic accuracy study.
Setting: Secondary care.
Participants: Adults (≥16 years old) presenting as inpatients or outpatients at 12 NHS hospital trusts in London, Slough, Oxford, Leicester and Birmingham with suspected active TB.
Interventions: The index tests—T-SPOT.TB, QFT-GIT, and new enzyme-linked immunospot assays utilising novel Mycobacterium tuberculosis antigens (Rv3615c, Rv2654, Rv3879c and Rv3873)—were verified against a composite reference standard applied by a panel of clinical experts blinded to IGRA results.
Main outcome measures: Sensitivity, specificity, predictive values and likelihood ratios were calculated to determine diagnostic accuracy. A decision tree model was developed to calculate the incremental costs and incremental health utilities (quality-adjusted life-years [QALYs]) of changing from current practice to using an IGRA as an initial rule out test.
Results: 363 patients had active TB (culture confirmed and highly probable TB cases), 439 had no active TB and 43 had an indeterminate final diagnosis. Comparing T-SPOT.TB and QFT-GIT, the sensitivities (95% CI) were 82.3% (77.7%–85.9%) and 67.3% (62.1%–72.2%) while specificities (95% CI) were 82.6% (78.6%–86.1%) and 80.4% (76.1%–84.1%), respectively. T-SPOT.TB was more sensitive than QFT-GIT [relative sensitivity (95% CI): i
1.22 (1.14–1.31); P 15 mg/day
1 (5.6)
1 (7.1)
0
14 (8.5)
16 (8.0)
Corticosteroids
