4.3.4.2.3 Overall grading Quality rating started at High for prospective and retrospective studies, and each major limitation brought the rating down by 1 increment to a minimum grade of Very Low, as explained for interventional reviews. 4.3.4.3 Diagnostic studies Risk of bias and indirectness of evidence for diagnostic data were evaluated by study using the Quality Assessment of Diagnostic Accuracy Studies version 2 (QUADAS-2) checklists (see appendix H in the NICE guidelines manual 2014236 ). Risk of bias and applicability in primary diagnostic accuracy studies in QUADAS-2 consists of 4 domains (see Table 5: Summary of QUADAS-2 with list of signalling, risk of bias and applicability questions.): patient selection index test reference standard flow and timing. Table 5: Summary of QUADAS-2 with list of signalling, risk of bias and applicability questions. Domain Patient selection Index test Reference standard Flow and timing Description Describe methods Describe the index Describe the Describe any patients Chronic Heart Failure Methods NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Domain Patient selection Index test Reference standard Flow and timing of patient selection. Describe included patients (prior testing, presentation, intended use of index test and setting) test and how it was conducted and interpreted reference standard and how it was conducted and interpreted who did not receive the index test(s) and/or reference standard or who were excluded from the 2 2 table (refer to flow diagram). Describe the time interval and any interventions between index test(s) and reference standard Signalling questions (yes/no/ unclear) Was a consecutive or random sample of patients enrolled? Were the index test results interpreted without knowledge of the results of the reference standard? Is the reference standard likely to correctly classify the target condition? Was there an appropriate interval between index test(s) and reference standard? 