title: Intravenous immunoglobulin for severe sepsis and septic shock: clinical effectiveness, cost-effectiveness and value of a further randomised controlled trial.
abstract: BACKGROUND
  Prior to investing in a large, multicentre randomised controlled trial (RCT), the National Institute for Health Research in the UK called for an evaluation of the feasibility and value for money of undertaking a trial on intravenous immunoglobulin (IVIG) as an adjuvant therapy for severe sepsis/septic shock.
  
  
  METHODS
  In response to this call, this study assessed the clinical and cost-effectiveness of IVIG (using a decision model), and evaluated the value of conducting an RCT (using expected value of information (EVI) analysis). The evidence informing such assessments was obtained through a series of systematic reviews and meta-analyses. Further primary data analyses were also undertaken using the Intensive Care National Audit & Research Centre Case Mix Programme Database, and a Scottish Intensive Care Society research study.
  
  
  RESULTS
  We found a large degree of statistical heterogeneity in the clinical evidence on treatment effect, and the source of such heterogeneity was unclear. The incremental cost-effectiveness ratio of IVIG is within the borderline region of estimates considered to represent value for money, but results appear highly sensitive to the choice of model used for clinical effectiveness. This was also the case with EVI estimates, with maximum payoffs from conducting a further clinical trial between £ 137 and £ 1,011 million.
  
  
  CONCLUSIONS
  Our analyses suggest that there is a need for a further RCT. Results on the value of conducting such research, however, were sensitive to the clinical effectiveness model used, reflecting the high level of heterogeneity in the evidence base.
authors.affiliation: Centre for Health Economics, University of York, Heslington, York, YO10 5DD, UK. marta.soares@york.ac.uk.
authors.forename: Marta O
authors.initials: MO
authors.lastname: Soares
authors.affiliation: School of Social and Community Medicine, 39 Whatley Road, University of Bristol, Bristol, BS8 2PS, UK. nicky.welton@bristol.ac.uk.
authors.forename: Nicky J
authors.initials: NJ
authors.lastname: Welton
authors.affiliation: Intensive Care National Audit & Research Centre, 24 High Holborn, London, WC1V 6AZ, UK. david.harrison@icnarc.org.
authors.forename: David A
authors.initials: DA
authors.lastname: Harrison
authors.affiliation: Centre for Health Economics, University of York, Heslington, York, YO10 5DD, UK. piia.peura@fimea.fi.
authors.forename: Piia
authors.initials: P
authors.lastname: Peura
authors.affiliation: Guy's and St Thomas' Hospital NHS Foundation Trust, Westminster Bridge Road, London, SE1 7EH, UK. Manu.Shankar-Hari@gstt.nhs.uk.
authors.forename: Manu
authors.initials: M
authors.lastname: Shankar-Hari
authors.affiliation: Intensive Care National Audit & Research Centre, 24 High Holborn, London, WC1V 6AZ, UK. sheila.harvey@icnarc.org.
authors.forename: Sheila E
authors.initials: SE
authors.lastname: Harvey
authors.affiliation: University of Warwick, Coventry, CV4 7AL, UK. J.J.Madan@warwick.ac.uk.
authors.forename: Jason
authors.initials: J
authors.lastname: Madan
authors.affiliation: School of Social and Community Medicine, 39 Whatley Road, University of Bristol, Bristol, BS8 2PS, UK. T.Ades@bristol.ac.uk.
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Ades
authors.affiliation: Intensive Care National Audit & Research Centre, 24 High Holborn, London, WC1V 6AZ, UK. kathy.rowan@icnarc.org.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Rowan
authors.affiliation: Centre for Health Economics, University of York, Heslington, York, YO10 5DD, UK. stephen.palmer@york.ac.uk.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Palmer
mesh_terms: D000368:Aged; D003362:Cost-Benefit Analysis / Q000379:methods*; D003661:Decision Support Techniques; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage* / Q000191:economics*; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic / Q000191:economics*; D018805:Sepsis / Q000188:drug therapy / Q000191:economics; D012772:Shock, Septic / Q000188:drug therapy* / Q000191:economics*; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome
chemical_list: D016756:Immunoglobulins, Intravenous