Assessment <strong>of</strong> diagnostic <strong>and</strong> prognostic accuracyTABLE 2 Studies <strong>and</strong> biomarkers included in the diagnostic accuracy <strong>review</strong>StudyAmodio 2007 52Apple 2008 53Apple 2008 54Apple 2009 55Bassan 2005 56Body 2011 57Body 2011 46Brown 2007 47Cete 2010 58Charpentier 2010 59Christ 2010 60Christenson 2001 61Collinson 2006 62Collinson 2006 48Di Serio 2005 63Ecollan 2007 64Eggers 2004 18Esporcatte 2007 65Garcia-Valdecasas 2011 49Guo 2006 66Haltern 2010 67Hjortshoj 2010 68Ilva 2009 50Ilva 2005 69Keating 2006 70Keller 2009 20Keller 2010 71Lefevre 2007 72Li 2010 73Liao 2009 74Mad 2007 75McCann 2008 76Mion 2007 77Naroo 2009 78Penttilä 2002 79Potsch 2006 51Relevant index test biomarkers in studyTnI, myoglobinTnITnITnI, CD40L, NT-pro-BNP, CRP, MMP9, MPOTnI, BNPTnI, H-FABP, myoglobin, BNP, MPOTnT, PAPP-A, CD40LST2TnT, H-FABP, myoglobinTnI, H-FABP, IMATnTIMATnI, TnTTnI, IMATnI, H-FABP, myoglobinTnI, H-FABP, myoglobinMyoglobinMPOTnI, H-FABP, myoglobinTnITnT, H-FABPH-FABP, myoglobin, IMATnI, H-FABPMyoglobinTnI, IMATnITnT, myoglobin, copeptinTnI, H-FABPTnT, H-FABPTnI, H-FABP, myoglobinH-FABPTnT, H-FABPTnI, H-FABP, myoglobinTnT, H-FABPMyoglobinCRP18NIHR Journals Library
DOI: 10.3310/hta17010 Health Technology Assessment 2013 Vol. 17 No. 1TABLE 2 Studies <strong>and</strong> biomarkers included in the diagnostic accuracy <strong>review</strong> (continued)StudyReichlin 2009 80Reichlin 2009 19Rudolf 2010 81Valle 2008 82Relevant index test biomarkers in studyCopeptinTnI, TnTTnI, MPOTnT, H-FABPCD4OL, CD4O lig<strong>and</strong>.Analysis <strong>of</strong> diagnostic accuracy studies <strong>of</strong> presentation troponinTables 7 <strong>and</strong> 8 show the reported sensitivity <strong>and</strong> specificity <strong>of</strong> each assay at key thresholds in each study<strong>of</strong> TnI <strong>and</strong> TnT, respectively. The studies used a variety <strong>of</strong> different assays <strong>and</strong> thresholds for positivity. Inconsequence, there is a wide range <strong>of</strong> reported values for sensitivity <strong>and</strong> specificity.We did not undertake <strong>meta</strong>-<strong>analysis</strong> across all studies because <strong>of</strong> variation in the assays <strong>and</strong> thresholdsused, with some studies using high thresholds with no clear basis. Instead, we undertook separateanalyses for TnI <strong>and</strong> TnT using the 99th percentile or 10% CV threshold, when these data were reported(Figures 7–10). The studies by Christ <strong>and</strong> Popp 60 <strong>and</strong> Reichlin et al. 19 reported data for more than oneassay in each potential <strong>analysis</strong>, so we selected data from one assay in each <strong>analysis</strong>. We also analysed thefollowing high-sensitivity assays using the 99th percentile (Figures 11–13):1. ADVIA Centaur Ultra troponin I (Siemens Healthcare, Basel, Switzerl<strong>and</strong>)2. Abbott Architect troponin I (Abbott Laboratories, IL, USA)3. Roche hsTnT. (Roche Diagnostics, Basel, Switzerl<strong>and</strong>).The results show that sensitivity <strong>and</strong> specificity for TnI were 77% (95% predictive interval 29–96%) <strong>and</strong>93% (95% predictive interval 46–100%), respectively, when the 99th percentile was used <strong>and</strong> 82% (95%predictive interval 40–97%) <strong>and</strong> 93% (95% predictive interval 74–98%) when the 10% CV was used. Thisapparently counterintuitive finding (lower sensitivity at a lower diagnostic threshold) is probably explainedby either r<strong>and</strong>om error or differences in the study populations or assays included in the two analyses.The corresponding results for TnT were 80% (95% predictive interval 33–97%) <strong>and</strong> 91% (95% predictiveinterval 53–99%) when the 99th percentile was used <strong>and</strong> 74% (95% predictive interval 34–94%) <strong>and</strong> 96%(95% predictive interval 76–99%) when the 10% CV was used, suggesting that different thresholds providea trade-<strong>of</strong>f between sensitivity <strong>and</strong> specificity. The differences between point estimates <strong>of</strong> sensitivity <strong>and</strong>specificity for TnI <strong>and</strong> TnT probably reflect differences in the assays or thresholds evaluated, the constituentstudy populations or r<strong>and</strong>om error, rather than a systematic difference between TnI <strong>and</strong> TnT. The credibleranges for the estimates differed markedly depending upon whether the pooled effect or predictive effectwas estimated, reflecting the marked heterogeneity between the studies. The predictive distribution is likelyto provide the most appropriate reflection <strong>of</strong> uncertainty <strong>and</strong> is used in the cost-effectiveness <strong>modelling</strong>.The high-sensitivity assays unsurprisingly had higher sensitivity but lower specificity, although withconsiderable uncertainty reflected in the wide predictive intervals for their estimates. The Roche HsTnTassay had a sensitivity <strong>of</strong> 96% (95% predictive interval 27–100%) <strong>and</strong> a specificity <strong>of</strong> 72% (95% predictiveinterval 3–96%). The ADVIA Centaur Ultra-TnI assay had a sensitivity <strong>of</strong> 86% (95% predictive interval22–96%) <strong>and</strong> a specificity <strong>of</strong> 89% (95% predictive interval 40–97%). The Abbot Architect troponin I assayhad a sensitivity <strong>of</strong> 83% (95% predictive interval 58–95%) <strong>and</strong> a specificity <strong>of</strong> 95% (95% predictive interval67–100%).These analyses compared high-sensitivity troponin index tests with a reference st<strong>and</strong>ard based on ast<strong>and</strong>ard troponin assay. We identified one study 60 that compared HsTnT at presentation with a reference© Queen’s Printer <strong>and</strong> Controller <strong>of</strong> HMSO 2013. This work was produced by Goodacre et al. under the terms <strong>of</strong> a commissioning contract issued by the Secretary <strong>of</strong> Statefor Health. This issue may be freely reproduced for the purposes <strong>of</strong> private research <strong>and</strong> study <strong>and</strong> extracts (or indeed, the full report) may be included in pr<strong>of</strong>essional journalsprovided that suitable acknowledgement is made <strong>and</strong> the reproduction is not associated with any form <strong>of</strong> advertising. Applications for commercial reproduction should beaddressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials <strong>and</strong> Studies Coordinating Centre, Alpha House, University <strong>of</strong> Southampton SciencePark, Southampton SO16 7NS, UK.19
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