Intravenous immunoglobulin for severe sepsis and septic shock: clinical effectiveness, cost-effectiveness and value of a further randomised controlled trial.

Marta O Soares,Manu Shankar-Hari,Stephen J Palmer,Sheila E Harvey,David A Harrison,Jason Madan,Kathryn M Rowan,Piia Peura,Anthony E Ades,Nicky J Welton

doi:10.1186/s13054-014-0649-z

Abstract

IntroductionPrior 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.MethodsIn 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.ResultsWe 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.ConclusionsOur 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.

Highlights

Prior to investing in a large, multicentre randomised controlled trial (RCT), the National Institute for Health Research in the United Kingdom (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
For the alternative clinical effectiveness models, the incremental cost effectiveness ratio (ICER) estimates vary between £16,177 per quality-adjusted life years (QALY) to IVIG being dominated by standard care (SC) alone. These results clearly demonstrate that any conclusions regarding the cost-effectiveness of IVIG appear highly sensitive to the choice of model used for clinical effectiveness
Our study examined the evidence for the clinical effectiveness of IVIG in severe sepsis and found significant heterogeneity between studies

Summary

Introduction

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. Intravenous immunoglobulin (IVIG) is a scarce blood product derived from human donor blood; it is currently subject to a Demand Management Programme by the United Kingdom (UK) Department of Health [4]. This product has been proposed as an adjuvant therapy for severe sepsis/septic shock since the 1980s. As a result of the heterogeneity across studies and the inconsistencies in their results, the majority conclude that there is currently insufficient evidence to recommend IVIG as an adjuvant therapy and that more evidence, in the form of a large, well-conducted RCT, is required

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Results

Discussion

Conclusion