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

Assessment of diagnostic and prognostic accuracyFor the review of biochemical markers, the following information was extracted for all studies whenreported: study characteristics (author, year of publication, journal, country, study design, setting);participant details (age, sex, presenting condition, inclusion and exclusion criteria); index test details(including time from pain onset to presentation or blood test, diagnostic threshold and assay); referencestandard details (including diagnostic threshold and assay, and timing of test); prevalence of MI and datafor a two-by-two table (TP, FN, FP, TN); sensitivity; specificity; and any additional potential relevant citationsfrom the reference list. Where a study presented prognostic data, the following additional informationwas extracted: whether the participants were TP or TN; duration of follow-up; method of data collection;mortality data; and data on non-fatal MI.For the review of CTCA and exercise ECG, the following information was extracted for all studies whenreported: study characteristics (author, year of publication, journal, country, study design, setting);participant details (age, sex, presenting condition, inclusion and exclusion criteria); index test details(including diagnostic threshold); reference standard details (including diagnostic threshold); prevalence ofCAD and data for a two-by-two table (TP, FN, FP, TN); sensitivity; specificity; and any additional potentialrelevant citations from the reference list. Where a study presented prognostic data, the followingadditional information was extracted: duration of follow-up; method of data collection; mortality data;data on non-fatal MI and any other MACE.Quality assessment strategyThe methodological quality of each diagnostic study in the review of biochemical markers was assessedby one reviewer (CC or MK) but checked by a second (CC or MK) using a modified version of the QualityAssessment of Diagnostic Accuracy Studies (QUADAS) tool 28 (a generic, validated, quality assessmentinstrument for diagnostic accuracy studies). The methodological quality of each included study in thereview of CTCA and exercise ECG was assessed by one reviewer (JL) but checked by a second (CC) using thesame modified version of the QUADAS tool. In all cases of doubt in either review, the principal investigator(SG) was consulted.The quality assessment items included from QUADAS 28 were the following: whether or not patients wererepresentative of those who would receive the test in practice, i.e. patients presenting to the emergencyservices or department with chest pain and suspected ACS; whether or not the reference standard waslikely to correctly classify the condition, i.e. was it based on the universal definition of MI; whether or notthe time period between onset of symptoms and reference standard and index test was clear enough tobe reasonably sure that index and reference tests are meaningful, i.e., were the two tests both conductedwithin the 12-hour time frame required for the reference standard; whether or not patients receivedsame reference standard regardless of index test result; whether or not the reference standard wasindependent of the index test (i.e. index test did not form part of reference standard); whether or notthe whole sample (or a random selection of the sample) received verification using a reference standardof diagnosis; whether or not the index test was interpreted without knowledge of reference standardresults; and whether or not the reference standard was interpreted without knowledge of index testresults (blinding).The following elements from the original QUADAS checklist were omitted either because they did notapply (e.g. inclusion criteria for the reviews was that all studies had to be prospective and patientsunselected, i.e. consecutive) or because they were not likely to impact on results in this case (e.g.descriptions of selection criteria or the tests): whether the study was prospective or retrospective; whetheror not selection criteria were clearly described; whether or not the reference standard was likely tocorrectly classify the condition; whether or not the execution of the reference standard was described insufficient detail to permit its replication; the relevance of index test to clinical practice; and whether ornot the execution of the index test was described in sufficient detail to permit its replication. The criterionconcerning whether or not there were any interpretable/intermediate test results and whether these werereported was only included in the CTCA/exercise ECG review as there was a risk of loss of data due touninterpretable results from imaging in this review, which did not apply to the biomarkers review. Study12NIHR Journals Library