title: Sepsis: the LightCycler SeptiFast Test MGRADE®, SepsiTest™ and IRIDICA BAC BSI assay for rapidly identifying bloodstream bacteria and fungi - a systematic review and economic evaluation.
abstract: Sepsis can lead to multiple organ failure and death. Timely and appropriate treatment can reduce in-hospital mortality and morbidity.
  
  
  
  To determine the clinical effectiveness and cost-effectiveness of three tests [LightCycler SeptiFast Test MGRADE(®) (Roche Diagnostics, Risch-Rotkreuz, Switzerland); SepsiTest(TM) (Molzym Molecular Diagnostics, Bremen, Germany); and the IRIDICA BAC BSI assay (Abbott Diagnostics, Lake Forest, IL, USA)] for the rapid identification of bloodstream bacteria and fungi in patients with suspected sepsis compared with standard practice (blood culture with or without matrix-absorbed laser desorption/ionisation time-of-flight mass spectrometry).
  
  
  
  Thirteen electronic databases (including MEDLINE, EMBASE and The Cochrane Library) were searched from January 2006 to May 2015 and supplemented by hand-searching relevant articles.
  
  
  
  A systematic review and meta-analysis of effectiveness studies were conducted. A review of published economic analyses was undertaken and a de novo health economic model was constructed. A decision tree was used to estimate the costs and quality-adjusted life-years (QALYs) associated with each test; all other parameters were estimated from published sources. The model was populated with evidence from the systematic review or individual studies, if this was considered more appropriate (base case 1). In a secondary analysis, estimates (based on experience and opinion) from seven clinicians regarding the benefits of earlier test results were sought (base case 2). A NHS and Personal Social Services perspective was taken, and costs and benefits were discounted at 3.5% per annum. Scenario analyses were used to assess uncertainty.
  
  
  
  For the review of diagnostic test accuracy, 62 studies of varying methodological quality were included. A meta-analysis of 54 studies comparing SeptiFast with blood culture found that SeptiFast had an estimated summary specificity of 0.86 [95% credible interval (CrI) 0.84 to 0.89] and sensitivity of 0.65 (95% CrI 0.60 to 0.71). Four studies comparing SepsiTest with blood culture found that SepsiTest had an estimated summary specificity of 0.86 (95% CrI 0.78 to 0.92) and sensitivity of 0.48 (95% CrI 0.21 to 0.74), and four studies comparing IRIDICA with blood culture found that IRIDICA had an estimated summary specificity of 0.84 (95% CrI 0.71 to 0.92) and sensitivity of 0.81 (95% CrI 0.69 to 0.90). Owing to the deficiencies in study quality for all interventions, diagnostic accuracy data should be treated with caution. No randomised clinical trial evidence was identified that indicated that any of the tests significantly improved key patient outcomes, such as mortality or duration in an intensive care unit or hospital. Base case 1 estimated that none of the three tests provided a benefit to patients compared with standard practice and thus all tests were dominated. In contrast, in base case 2 it was estimated that all cost per QALY-gained values were below £20,000; the IRIDICA BAC BSI assay had the highest estimated incremental net benefit, but results from base case 2 should be treated with caution as these are not evidence based.
  
  
  
  Robust data to accurately assess the clinical effectiveness and cost-effectiveness of the interventions are currently unavailable.
  
  
  
  The clinical effectiveness and cost-effectiveness of the interventions cannot be reliably determined with the current evidence base. Appropriate studies, which allow information from the tests to be implemented in clinical practice, are required.
  
  
  
  This study is registered as PROSPERO CRD42015016724.
  
  
  
  The National Institute for Health Research Health Technology Assessment programme.
authors.affiliation: School of Health and Related Research, University of Sheffield, Sheffield, UK.
authors.forename: Matt
authors.initials: M
authors.lastname: Stevenson
authors.affiliation: School of Health and Related Research, University of Sheffield, Sheffield, UK.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Pandor
authors.affiliation: School of Health and Related Research, University of Sheffield, Sheffield, UK.
authors.forename: Marrissa
authors.initials: M
authors.lastname: Martyn-St James
authors.affiliation: School of Health and Related Research, University of Sheffield, Sheffield, UK.
authors.forename: Rachid
authors.initials: R
authors.lastname: Rafia
authors.affiliation: School of Health and Related Research, University of Sheffield, Sheffield, UK.
authors.forename: Lesley
authors.initials: L
authors.lastname: Uttley
authors.affiliation: School of Health and Related Research, University of Sheffield, Sheffield, UK.
authors.forename: John
authors.initials: J
authors.lastname: Stevens
authors.affiliation: School of Health and Related Research, University of Sheffield, Sheffield, UK.
authors.forename: Jean
authors.initials: J
authors.lastname: Sanderson
authors.affiliation: School of Health and Related Research, University of Sheffield, Sheffield, UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: Wong
authors.affiliation: Warwick Clinical Trials Unit, University of Warwick, Coventry, UK.|Heart of England NHS Foundation Trust, Coventry, UK.
authors.forename: Gavin D
authors.initials: GD
authors.lastname: Perkins
authors.affiliation: Centre for Experimental Medicine, Queen's University Belfast, Belfast, UK.|Belfast Health and Social Care Trust, The Royal Hospitals, Belfast, UK.
authors.forename: Ronan
authors.initials: R
authors.lastname: McMullan
authors.affiliation: Institute of Inflammation and Repair, University of Manchester, Manchester, UK.|Salford Royal NHS Foundation Trust, Salford, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Dark
mesh_terms: D000367:Age Factors; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D016470:Bacteremia / Q000175:diagnosis* / Q000453:epidemiology; D003362:Cost-Benefit Analysis; D003428:Cross Infection / Q000175:diagnosis; D064147:Febrile Neutropenia / Q000453:epidemiology; D016469:Fungemia / Q000175:diagnosis* / Q000453:epidemiology; D005858:Germany; D017052:Hospital Mortality; D006801:Humans; D017059:Models, Econometric; D018803:Models, Economic; D016133:Polymerase Chain Reaction / Q000191:economics* / Q000379:methods* / Q000592:standards; D019057:Quality-Adjusted Life Years; D012680:Sensitivity and Specificity; D018805:Sepsis / Q000175:diagnosis / Q000453:epidemiology; D013673:Technology Assessment, Biomedical; D006113:United Kingdom
chemical_list: D000900:Anti-Bacterial Agents