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

More documents

Recommendations

Info

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
DOI: 10.3310/hta17010 Health Technology Assessment 2013 Vol. 17 No. 1quality was assessed with each item scored as ‘yes’, ‘no’ or ‘unclear’. Further details on the modifiedversion of the QUADAS tool are provided in Appendix 2.The quality assessment for prognostic studies of biomarkers, exercise ECG and CTCA was conducted usingan adapted version of the framework described by Altman. 29 The assessment asked the following sevenquestions of each study:1. Sample of patients Are inclusion criteria defined?2. Sample of patients Are characteristics described (age and sex)?3. Outcome Is a MACE defined in the methods section?4. Outcome Is a MACE identification and definition independent of the index test?5. Outcome Is a MACE outcome recorded for at least 80% of the cohort from baseline episode?6. Analysis Was a multivariate analysis undertaken (were other variables, other than our variable ofinterest, included in the analysis)?7. Analysis Is troponin measured and included in the multivariate analysis, or is analysis stratified bytroponin or limited to those with a negative troponin?Questions 1 and 2 assessed adequacy of reporting. Question 3 aimed to determine whether or not theoutcome of interest (MACE) appeared to have been defined a priori by the researchers (i.e. in the methodssection rather than the results section). Question 4 aimed to determine whether or not a presentingdiagnosis (such as MI) that could have been associated with a positive index test was incorporated in thedefinition of MACEs. Question 5 assessed adequacy of follow-up. Although this was an inclusion criterionfor the review, 80% follow-up was not always clearly reported or achieved at all time points. Question 6assessed whether or not the study had explored beyond an association between the index test and MACEsto determine whether or not the biomarker added prognostic value beyond routine assessment. Question7 assessed whether this analysis was stratified by or adjusted for troponin, to determine whether thebiomarker added prognostic value to that provided by troponin.The methodological quality of each prognostic study in the review of biochemical markers was assessedby one reviewer (SG or CC) but checked by a second (SG or CC) using this modified version of the Altmancriteria. 29 The methodological quality of each included study in the review of CTCA and exercise ECG wasassessed by one reviewer (JL) but checked by a second (FM) using these same criteria. In all cases of doubtin either review, the principal investigator (SG) was consulted.Methods of data synthesisThe analysis was conducted using Bayesian Markov chain Monte Carlo simulation. In general, there areadvantages of the Bayesian approach over a Classical approach, including the ability to (1) analyse complexmodels exactly; (2) incorporate external evidence in addition to sample data; and (3) make probabilisticstatements about parameters. In particular, the approach allowed the direct use of a binomial likelihoodfor the sample data, including for studies with very small or zero counts; the ability to incorporateuncertainty in the estimate of the between-study standard deviation (SD), including in studies withrelatively few studies; 30 and the ability to generate probability distributions that represent parameteruncertainty about inputs to the economic model.The use of a random-effects model is motivated a priori by the assumption that the true sensitivitiesand specificities vary according to the study but that they arise from a common (bivariate) populationdistribution. Heterogeneity is common in meta-analyses of diagnostic test data and the results of theseanalyses are no exception. The pooled effects presented in the forest plots represent the means of thepopulation of sensitivities and specificities, and these are the parameters that are commonly presented asthe results of a meta-analysis. Also presented with the forest plots are predictive effects; these representthe range of estimates that we might expect to see in the population taking into account uncertaintyin both the estimate of the mean sensitivity and specificity and the uncertainty in the estimates of the© 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.13
Page 1: Health Technology AssessmentVOLUME
Page 7: DOI: 10.3310/hta17010 Health Techno
Page 10 and 11: ContentsAppendix 5 Expected discoun
Page 13 and 14: DOI: 10.3310/hta17010 Health Techno
Page 19: DOI: 10.3310/hta17010 Health Techno
Page 22 and 23: BackgroundTABLE 1 Hospital admissio
Page 24 and 25: Background2. investigation of the c
Page 26 and 27: BackgroundComputed tomographic coro
Page 28 and 29: Research questionsiii. the diagnost
Page 30 and 31: Assessment of diagnostic and progno
Page 82 and 83:
Assessment of diagnostic and progno
Page 84 and 85:
Page 86 and 87:
Page 88 and 89:
Page 91 and 92:
DOI: 10.3310/hta17010 Health Techno
Page 93 and 94:
Page 95 and 96:
Page 97 and 98:
Page 99 and 100:
Page 101 and 102:
Page 103 and 104:
Page 105 and 106:
Page 107 and 108:
Page 109 and 110:
Page 111 and 112:
Page 113 and 114:
Page 115 and 116:
Page 117 and 118:
Page 119 and 120:
Page 121 and 122:
Page 123 and 124:
Page 125:
Page 128 and 129:
Discussionspecificity were 62% (95%
Page 130 and 131:
Discussionneed for revascularisatio
Page 132 and 133:
Discussionchanges in sensitivity an
Page 134 and 135:
Discussionuncertainty about these p
Page 136 and 137:
Discussiontroponin assays have bett
Page 138 and 139:
ConclusionsSuggested research prior
Page 141 and 142:
Page 143 and 144:
Page 145 and 146:
Page 147 and 148:
Page 149 and 150:
Page 151:
Page 154 and 155:
Appendix 144. heart-type fatty acid
Page 156 and 157:
Appendix 1135. interleukin 33.mp. (
Page 158 and 159:
Appendix 147. 37 and 45 (529)48. li
Page 161:
Page 164 and 165:
Appendix 313. Fernandez Portales JG
Page 166 and 167:
Appendix 346. Luscher MS, Ravkilde
Page 168 and 169:
Appendix 316. Rao SV, Ohman EM, Gra
Page 171 and 172:
Page 173 and 174:
Page 175 and 176:
Page 177 and 178:
Page 179 and 180:
Page 181 and 182:
Page 183:
Page 187 and 188:
Page 189 and 190:
Page 191 and 192:
Page 193 and 194:
Page 195:
Page 198 and 199:
Appendix 9Clinical diagnosis of NST
Page 200 and 201:
Appendix 9respectively. Exercise EC
Page 202 and 203:
Appendix 93. Two reviewers will mak
Page 204 and 205:
Appendix 9The methodology used in t
Page 206 and 207:
Appendix 9ES (Information Resources
Page 208:
Appendix 923. Westwood ME, Whiting
show all

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

Create successful ePaper yourself

Delete template?

Save as template?