© 2012, Crown Copyright.
Included under terms of UK Non-commercial Government License.
Bookshelf ID: NBK97451
< PrevNext >
NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.
< PrevNext >
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 Technology Assessment, No. 16.7
MO Soares, NJ Welton, DA Harrison, P Peura, M Shankar-Hari, SE Harvey, JJ Madan, AE Ades, SJ Palmer, and KM Rowan.
Author Information and AffiliationsSouthampton (UK): NIHR Journals Library; 2012 Feb.
Abstract
Background:
Sepsis is a syndrome characterised by a systemic inflammatory response to infection that leads to rapid acute organ failure and potentially rapid decline to death. Intravenous immunoglobulin (IVIG), a blood product derived from human donor blood, has been proposed as an adjuvant therapy for sepsis.
Objectives:
To describe current practice in the management of adult patients severely ill with sepsis (severe sepsis or septic shock) in the UK; to assess the clinical effectiveness of IVIG for severe sepsis and septic shock and to obtain the appropriate inputs for the relative efficacy parameters, and the key uncertainties associated with these parameters, required to populate the decision model; to develop a decision-analytic model structure and identify key parameter inputs consistent with the decision problem and relevant to an NHS setting; and to populate the decision model and determine the cost-effectiveness of IVIG and to estimate the value of additional primary research.
Data sources:
Existing literature on IVIG and severe sepsis. Existing case-mix and outcome data on critical care admissions. Survey data on management of admissions with severe sepsis. Databases searched for clinical effectiveness were Cochrane Infectious Diseases Group Specialized Trials Register, the Cochrane Trials Register, MEDLINE and EMBASE. Dates searched were 1 January 2002 to 2 October 2009 to update previous Cochrane review. Databases searched for cost-effectiveness were NHS Economic Evaluation Database (NHS EED) to 2 October 2009, MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations and EMBASE to 20 October 2009.
Review methods:
Systematic literature searching with data extraction, descriptive analysis and clinical effectiveness and cost-effectiveness modelling of IVIG in severe sepsis. Additional primary data analysis. Expected value of information (EVI) analysis.
Results:
Our meta-analysis, the first to simultaneously allow for type of IVIG (IVIG or immunoglobulin M-enriched polyclonal IVIG), choice of control (no treatment or albumin), study quality/publication bias and other potential covariates, indicated that the treatment effect of IVIG on mortality for patients with severe sepsis is borderline significant with a large degree of heterogeneity in treatment effect between individual studies. Modelling indicated that there were issues with bias associated with trial methodology, publication and small-study effects with the current evidence. The large degree of heterogeneity in treatment effects between studies, however, could be explained (best-fitting model) by a measure of study quality (i.e. use of albumin as control – as an indicator of proper blinding to treatment as a proxy for study quality – associated with decreased effect) and duration of IVIG therapy (longer duration associated with increased effect). In-depth discussion within the Expert Group on duration of IVIG therapy, with daily dose and total dose also clearly inter-related, indicated no clear clinical rationale for this association and exposed a lack of evidence on the understanding of the mechanism of action of IVIG in severe sepsis. Although the EVI analyses suggested substantial expected net benefit from a large, multicentre randomised controlled trial (RCT) evaluating the clinical effectiveness of IVIG, the remaining uncertainties around the design of such a study mean that we are unable to recommend it at this time.
Limitations:
As has been identified in previous meta-analyses, there are issues with the methodological quality of the available evidence.
Conclusions:
Although the results highlight the value for money obtained in conducting further primary research in this area, the biggest limitation for such research regards the uncertainties over the mechanism of action of IVIG and the heterogeneous nature of severe sepsis. Resolving these would allow for better definition of the plausibility of the effectiveness scenarios presented and, consequently, a better understanding of the cost-effectiveness of this treatment. This information would also inform the design of future, primary evaluative research. Our recommendations for future research focus on filling the knowledge gaps to inform a future multicentre RCT prior to recommending its immediate design and conduct.
Funding:
The National Institute for Health Research Health Technology Assessment programme.
Contents
- NIHR Health Technology Assessment programme
- List of abbreviations
- Executive summary
- 1. Introduction
- 2. Survey of the management of severe sepsis in UK critical-care units
- 3. Clinical effectiveness of intravenous immunoglobulin for severe sepsis and septic shock
- 4. Cost-effectiveness and value of information analysis – informing the model structure and identifying relevant data sources and inputs
- 5. Cost-effectiveness analysis – analytic methods and results
- 6. Value of information analysis - analytic methods and results
- 7. Conclusions
- Acknowledgements
- References
- Appendix 1 Questionnaire for the survey of the management of severe sepsis in UK critical-care units
- Appendix 2 Search strategies
- Appendix 3 Quality assessment of published cost-effectiveness evidence for intravenous immunoglobulin
- Appendix 4 Critical-care unit and hospital mortality data from the Intensive Care National Audit & Research Centre Case Mix Programme Database
- Appendix 5 Technical description of decision model and methods for the expected value of sample information
- Appendix 6 Logistic regression results and predictions for short-term mortality
- Appendix 7 Results of parametric survival models for long-term survival
- Appendix 8 Length of stay in the critical-care unit and in hospital from the ICNARC Case Mix Programme Database
- Appendix 9 Summary of input parameters and sources
- Appendix 10 Cost-effectiveness results for subgroups
- Appendix 11 Study protocol
- Health Technology Assessment programme
Suggested citation:
Soares MO, Welton NJ, Harrison DA, Peura P, Shankar-Hari M, Harvey SE, et al. 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, metaanalysis and value of information analysis. Health Technol Assess 2012;16(7).
Declared competing interests of authors: none.
The research reported in this issue of the journal was commissioned by the HTA programme as project number 08/70/01. The contractual start date was in May 2009. The draft report began editorial review in September 2010 and was accepted for publication in February 2011. As the funder, by devising a commissioning brief, the HTA programme specified the research question and study design. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors' report and would like to thank the referees for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.
The views expressed in this publication are those of the authors and not necessarily those of the HTA programme or the Department of Health.
- NLM CatalogRelated NLM Catalog Entries
- Intravenous immunoglobulin for severe sepsis and septic shock: clinical effectiveness, cost-effectiveness and value of a further randomised controlled trial.[Crit Care. 2014]Intravenous immunoglobulin for severe sepsis and septic shock: clinical effectiveness, cost-effectiveness and value of a further randomised controlled trial.Soares MO, Welton NJ, Harrison DA, Peura P, Shankar-Hari M, Harvey SE, Madan J, Ades AE, Rowan KM, Palmer SJ. Crit Care. 2014 Dec 1; 18(6):649. Epub 2014 Dec 1.
- Review Systematic review and modelling of the cost-effectiveness of cardiac magnetic resonance imaging compared with current existing testing pathways in ischaemic cardiomyopathy.[Health Technol Assess. 2014]Review Systematic review and modelling of the cost-effectiveness of cardiac magnetic resonance imaging compared with current existing testing pathways in ischaemic cardiomyopathy.Campbell F, Thokala P, Uttley LC, Sutton A, Sutton AJ, Al-Mohammad A, Thomas SM. Health Technol Assess. 2014 Sep; 18(59):1-120.
- The future of Cochrane Neonatal.[Early Hum Dev. 2020]The future of Cochrane Neonatal.Soll RF, Ovelman C, McGuire W. Early Hum Dev. 2020 Nov; 150:105191. Epub 2020 Sep 12.
- Review What is the value of routinely testing full blood count, electrolytes and urea, and pulmonary function tests before elective surgery in patients with no apparent clinical indication and in subgroups of patients with common comorbidities: a systematic review of the clinical and cost-effective literature.[Health Technol Assess. 2012]Review What is the value of routinely testing full blood count, electrolytes and urea, and pulmonary function tests before elective surgery in patients with no apparent clinical indication and in subgroups of patients with common comorbidities: a systematic review of the clinical and cost-effective literature.Czoski-Murray C, Lloyd Jones M, McCabe C, Claxton K, Oluboyede Y, Roberts J, Nicholl JP, Rees A, Reilly CS, Young D, et al. Health Technol Assess. 2012 Dec; 16(50):i-xvi, 1-159.
- Review Intravenous immunoglobulin for treating sepsis, severe sepsis and septic shock.[Cochrane Database Syst Rev. 2013]Review Intravenous immunoglobulin for treating sepsis, severe sepsis and septic shock.Alejandria MM, Lansang MA, Dans LF, Mantaring JB 3rd. Cochrane Database Syst Rev. 2013 Sep 16; 2013(9):CD001090. Epub 2013 Sep 16.
- An Evaluation of the Feasibility, Cost and Value of Information of a Multicentre...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
- Gastrostomy versus nasogastric tube feeding for chemoradiation patients with hea...Gastrostomy versus nasogastric tube feeding for chemoradiation patients with head and neck cancer: the TUBE pilot RCT
- Uterotonic drugs to prevent postpartum haemorrhage: a network meta-analysisUterotonic drugs to prevent postpartum haemorrhage: a network meta-analysis
- Exercise- and strategy-based physiotherapy-delivered intervention for preventing...Exercise- and strategy-based physiotherapy-delivered intervention for preventing repeat falls in people with Parkinson’s: the PDSAFE RCT
- BREATHER (PENTA 16) short-cycle therapy (SCT) (5 days on/2 days off) in young pe...BREATHER (PENTA 16) short-cycle therapy (SCT) (5 days on/2 days off) in young people with chronic human immunodeficiency virus infection: an open, randomised, parallel-group Phase II/III trial
Your browsing activity is empty.
Activity recording is turned off.
See more...