Assessment <strong>of</strong> diagnostic <strong>and</strong> prognostic accuracyTABLE 19 Studies included in the prognostic accuracy <strong>review</strong>StudyApple 2007 87Apple 2011 88Bholasingh 2003 89Blum 2003 90Body 2011 46Brennan 2003 91Brown 2007 92Brown 2007 47Brugger-Anderson 2008 93Cameron 94Collinson 2006 48Consuegra–Sanchez 2008 95De Winter 1996 96Eggers 2008 85Eggers 2008 97Fromm 2001 98Garcia-Valdecasas 2011 49Green 2000 99Hillis 2003 100Ilva 2009 50Jaffery 2008 101Jernberg 2002 102Kavsak 2009 103Kontos 2007 104Laterza 2004 105Lim 2002 106Lund 2003 107Manini 2009 108Markovic 2010 109Mathew 1999 110McCann 2009 111McCord 2003 112Included index testbiomarkers in studyBNP, hsCRP, MMP9, MPOMPOCRPCRPPAPP-ACRP, MPOBNP, myoglobinST-2BNP, hsCRPBNP, hsCRP, myoglobinIMAIMAMyoglobinNT-pro-BNP, CRPNT-pro-BNP, CRPMyoglobinH-FABP, myoglobinMyoglobinMyoglobinH-FABPMyoglobinNT-pro-BNPPAPP-AMyoglobinPAPP-AMyoglobinPAPP-AIMABNP, hsCRPMyoglobinBNP, H-FABP, hsCRP, MMP9,MPO, PAPP-AMyoglobinMenown 2003 113 hsCRP, interleukin 6Mockel 2008 86Newby 2001 114NT-pro-BNP, hsCRPMyoglobin56NIHR Journals Library
DOI: 10.3310/hta17010 Health Technology Assessment 2013 Vol. 17 No. 1TABLE 19 Studies included in the prognostic accuracy <strong>review</strong> (continued)StudyOrdonez-Llanos 2006 115Pontiz 2009 116Potsch 2006 51Sonel 2000 117Svensson 2004 118Szymanski 2007 119Van Domburg 2000 120Viswanathan 2010 121Yamashita 2010 122Included index testbiomarkers in studyMyoglobinBNPCRPMyoglobinMyoglobinMyoglobinMyoglobinH-FABPNT-pro-BNP, H-FABPhs-CRP, high-sensitivity C-reactive protein.data. Two studies 44,45 were subsequently excluded because data could have overlapped with otherincluded studies. 85,86Description <strong>of</strong> studies included in the prognostic biomarker <strong>review</strong>The characteristics <strong>of</strong> the included studies are outlined in Table 20. Most studies did not report selectioncriteria beyond those needed to define acute chest pain or suspected ACS. However, some studiesexcluded patients with high clinical risk, ECG changes <strong>of</strong> ischaemia or positive admission troponin orCK-MB. The duration <strong>of</strong> follow-up ranged from the duration <strong>of</strong> inpatient stay to 5 years. Definitions <strong>of</strong>MACEs varied between studies, with some studies predicting only mortality, whereas others predicted arange <strong>of</strong> outcomes. Where more than one definition <strong>of</strong> a MACE was used or more than one time point forfollow-up was reported, we used the most inclusive definition <strong>and</strong> the longest duration <strong>of</strong> follow-up.Quality assessment <strong>of</strong> studies included in the prognostic biomarkers <strong>review</strong>Table 21 shows the results <strong>of</strong> quality assessment. Nearly all the studies reported adequately, definedMACEs in the methods section, did not incorporate presenting diagnosis in the definition <strong>of</strong> a MACE <strong>and</strong>achieved adequate follow-up. However, only around half undertook <strong>analysis</strong> that went beyond testing orestimating the association between the biomarker <strong>and</strong> a MACE, <strong>and</strong> only a minority tested whether or notthe biomarker added prognostic value to that provided by troponin.Analysis <strong>of</strong> prognostic biomarker studiesTable 22 shows the main univariate analyses reported in the prognostic biomarker studies, i.e. any <strong>analysis</strong>that tested or estimated the association between a biomarker <strong>and</strong> a MACE. There was substantial variationin the analyses reported. Some only used a hypothesis test for the association between a biomarker <strong>and</strong> aMACE, others estimated parameters [sensitivity, specificity or area under receiver operating characteristic(AUROC)] for discriminating between patients with <strong>and</strong> without MACEs, <strong>and</strong> others estimated the oddsratio (OR), RR or hazard ratio (HR) for MACEs for quartiles <strong>of</strong> the biomarker or a biomarker level above aspecified threshold. Many <strong>of</strong> these analyses report a significant association but they are <strong>of</strong> limited valuebecause they do not tell us whether or not the biomarker in question provides prognostic informationbeyond that already available from clinical assessment, ECG <strong>and</strong> troponin measurement.Some <strong>of</strong> the studies used multivariate <strong>analysis</strong> to adjust for known predictors <strong>of</strong> MACEs <strong>and</strong> determinewhether or not the biomarkers predicted a MACE when other variables were taken into account. Theseare shown in Table 23. If troponin was included as a covariate then this <strong>analysis</strong> could potentially showwhether the biomarker provided additional prognostic information to troponin. The findings showed© 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.57
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