Systematic review, meta-analysis and economic modelling of ...

DOI: 10.3310/hta17010 Health Technology Assessment 2013 Vol. 17 No. 1TABLE 19 Studies included in the prognostic accuracy review (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 of studies included in the prognostic biomarker reviewThe characteristics of 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 of ischaemia or positive admission troponin orCK-MB. The duration of follow-up ranged from the duration of inpatient stay to 5 years. Definitions ofMACEs varied between studies, with some studies predicting only mortality, whereas others predicted arange of outcomes. Where more than one definition of a MACE was used or more than one time point forfollow-up was reported, we used the most inclusive definition and the longest duration of follow-up.Quality assessment of studies included in the prognostic biomarkers reviewTable 21 shows the results of quality assessment. Nearly all the studies reported adequately, definedMACEs in the methods section, did not incorporate presenting diagnosis in the definition of a MACE andachieved adequate follow-up. However, only around half undertook analysis that went beyond testing orestimating the association between the biomarker and a MACE, and only a minority tested whether or notthe biomarker added prognostic value to that provided by troponin.Analysis of prognostic biomarker studiesTable 22 shows the main univariate analyses reported in the prognostic biomarker studies, i.e. any analysisthat tested or estimated the association between a biomarker and a MACE. There was substantial variationin the analyses reported. Some only used a hypothesis test for the association between a biomarker and aMACE, others estimated parameters [sensitivity, specificity or area under receiver operating characteristic(AUROC)] for discriminating between patients with and without MACEs, and others estimated the oddsratio (OR), RR or hazard ratio (HR) for MACEs for quartiles of the biomarker or a biomarker level above aspecified threshold. Many of these analyses report a significant association but they are of limited valuebecause they do not tell us whether or not the biomarker in question provides prognostic informationbeyond that already available from clinical assessment, ECG and troponin measurement.Some of the studies used multivariate analysis to adjust for known predictors of MACEs and 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 analysis could potentially showwhether the biomarker provided additional prognostic information to troponin. The findings showed© Queen’s Printer and Controller of HMSO 2013. This work was produced by Goodacre et al. under the terms of a commissioning contract issued by the Secretary of Statefor Health. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journalsprovided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should beaddressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton SciencePark, Southampton SO16 7NS, UK.57