MSH contributed to the interpretation of the data and findings. 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. Namitecan 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. Introduction Sepsis is a clinical syndrome defined by the presence of both infection and a systemic inflammatory response; sepsis is defined as severe when associated with, or complicated by, organ dysfunction [1]. Severe sepsis may induce septic shock, defined as hypotension persisting despite adequate fluid resuscitation [2]. There is evidence indicating an increasing incidence of severe sepsis treated in critical care in England, Wales and Northern Ireland, rising from 50 to 70 cases per 100,000 population per year between 1995 and 2005 – these cases being associated with approximately 31,000 episodes of severe sepsis and Namitecan 15,000 in-hospital deaths per year [3]. Being a serious, life-threatening condition, severe sepsis is expected to be associated with substantial healthcare costs and a significant impact on quality of life. 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. However, the mechanisms of action Rabbit polyclonal to LRCH3 of IVIG are complex and are not yet fully understood. Despite this, a number of (predominantly small) randomised controlled trials (RCTs) have been conducted, and numerous systematic reviews and meta-analyses have been undertaken to synthesise their findings [5-8]. 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. Prior to investing in a large, multicentre RCT, the Health Technology Assessment (HTA) Programme of the National Institute for Health Research in the UK called for an evaluation of the feasibility and value for money of undertaking such a trial (that is, whether or not the costs of undertaking the trial are outweighed by the potential benefit of the resulting information). The Namitecan aim of this manuscript is to report our findings in response to this call by assessing the clinical and cost-effectiveness of IVIG in severe sepsis/septic shock in adults, and evaluating the value of conducting a large, multicentre RCT using an expected value of information (EVI) analysis. EVI offers a methodological framework that explicitly considers the uncertainty surrounding the decision by a healthcare system to adopt a health technology and values the additional information, which may be generated by further research, in a way that is consistent with the objectives and resource constraints of heathcare provision [9]. A full technical report of this research is published elsewhere [10]. Here, we provide a summary of the evaluation of clinical effectiveness, cost-effectiveness, and value of information of IVIG in critically ill adults with severe sepsis/septic shock, undertaken to inform the UK policy context. We discuss the implications arising from this policy-driven evidence review. Methods We conducted a series of formal systematic reviews and undertook additional primary data analysis to develop and populate a decision analytic model. Details of each review and data sources are offered in the full technical statement [10]. The decision model evaluated the cost-effectiveness of IVIG as an adjunctive treatment to standard care for the management of adults with severe.
MSH contributed to the interpretation of the data and findings