Protocol for a parallel economic evaluation of a trial comparing two surgical strategies in severe complicated...

The risk of death in severe complicated intra-abdominal sepsis (SCIAS) remains high despite decades of surgical and antimicrobial research. New management strategies are required to improve outcomes. The Closed Or Open after Laparotomy (COOL) trial investigates an open-abdomen (OA) approach with active negative pressure peritoneal therapy. This therapy is hypothesized to better manage peritoneal bacterial contamination, drain inflammatory ascites, and reduce the risk of intra-abdominal hypertension leading to improved survival and decreased complications. The total costs and cost-effectiveness of this therapy (as compared with standard fascial closure) are unknown.

We propose a parallel cost-utility analysis of this intervention to be conducted alongside the 1-year trial, extrapolating beyond that using decision analysis. Using resource use metrics (e.g., length of stay, re-admissions) from patients at all study sites and microcosting data from patients enrolled in Calgary, Alberta, the mean cost difference between treatment arms will be established from a publicly-funded health care payer perspective. Quality of life will be measured at 6 months and 1 year postoperatively with the Euroqol EQ-5D-5 L and SF-36 surveys. A within-trial analysis will establish cost and utility at 1 year, using a bootstrapping approach to provide confidence intervals around an estimated incremental cost-effectiveness ratio. If neither operative strategy is economically dominant, Markov modeling will be used to extrapolate the cost per quality-adjusted life years gained to 2-, 5-, 10-year, and lifetime horizons. Future costs and benefits will be discounted at 1.5% per annum. A cost-effectiveness acceptability curve will be generated using Monte Carlo simulation. If all trial outcomes are similar, the primary analysis will default to a cost-minimization approach. Subgroup analysis will be carried out for patients with and without septic shock at presentation, and for patients whose initial APACHE II scores are > 20 versus ≤ 20.

In addition to an estimate of the clinical effectiveness of an OA approach for SCIAS, an understanding of its cost effectiveness will be required prior to its adoption in any resource-constrained environment. We will estimate this key parameter for use by clinicians and policymakers.

ClinicalTrials.gov, NCT03163095, registered May 22, 2017.