IVIG: An evaluation of the feasibility, cost and value of information of a multicentre randomised controlled trial of intravenous immunoglobulin for sepsis (severe sepsis and septic shock)
Background
Severe infection (severe sepsis) can lead to organ failure (e.g. kidney failure) and can be life-threatening. Immunoglobulins are proteins produced by the immune system (the body’s defence system) that help the body to fight infection. Intravenous immunoglobulin (IVIG) is a blood product that combines immunoglobulins from several donors and may be useful for treating patients with a severe infection.
The purpose of this study was to find out how IVIG is currently used by doctors for treating patients with a severe infection and if a large clinical trial should be carried out to investigate whether IVIG improves outcome in these patients and is cost-effective.
Design
To address this question, we gathered, reviewed and combined all available research evidence and primary data on the management and treatment of severe sepsis to include, not only the use and effectiveness of IVIG, but other effective interventions in severe sepsis. In addition, we conducted a survey current practice, or usual care, in the NHS and clinicians’ views of the potential future role for IVIG.
Results
123 out of 231 adult intensive care units completed the survey. Over 70% indicated that they used ‘bundles’ for the resuscitation and management of patients with severe sepsis and ~60% reported using IVIG for the management of patients with sepsis. When reviewing the existing research evidence, we found a large degree of variation in the effect of treatment but bordered on showing benefit of treatment with IVIG. The cost-effectiveness analysis showed treatment with IVIG is on the borderline of showing value for money within the NHS but the results appear highly sensitive to the choice of model used for clinical effectiveness.
Conclusion
Our results showed that there is value for money in conducting further research in this area. However, before carrying out a large clinical trial, further research needs to be carried out to understand better how IVIG works. This would also allow a better understanding of the cost-effectiveness of this treatment. Our recommendations are that future research should focus on filling the knowledge gaps about IVIG to help researchers plan a future clinical trial.
Study lead: Kathy Rowan
Study funding: National Institute for Health Research (NIHR) – Health Technology Assessment (HTA) Programme (Project: 08/70/01)
Publications
Welton NJ, Soares MO, Palmer S, Ades AE, Harrison D, Shankar-Hari M, Rowan KM. Accounting for Heterogeneity in Relative Treatment Effects for Use in Cost-Effectiveness Models and Value-of-Information Analyses. Med Decis Making 2015; 35(5):608-21. http://dx.doi.org/10.1177/0272989x15570113 Soares MO, Welton NJ, Harrison DA, Peura P, Shankar-Hari M, Harvey SE, Madan J, Ades AE, Rowan KM, Palmer SJ. Intravenous immunoglobulin for severe sepsis and septic shock: clinical effectiveness, cost-effectiveness and value of a further randomised controlled trial. Crit Care 2014; 18(6):649. http://dx.doi.org/10.1186/s13054-014-0649-z Soares MO, Welton NJ, Harrison DA, Peura P, Shankar- Hari M, Harvey SE, Madan JJ, Ades AE, Palmer SJ, Rowan KM. An evaluation of the feasibility, cost and value of information of a multicentre randomised controlled trial of intravenous immunoglobulin for sepsis (severe sepsis and septic shock): incorporating a systematic review, meta-analysis and value of information analysis. Health Technol Assess 2012; 16(7):1-186. http://dx.doi.org/10.3310/hta16070 Shankar-Hari M, Spencer J, Sewell WA, Rowan KM, Singer M. Bench-to-bedside review: Immunoglobulin therapy for sepsis - biological plausibility from a critical care perspective. Crit Care 2012; 16(2):206. http://dx.doi.org/10.1186/cc10597
