Application of a Framework to Assess the Usefulness of Alternative Sepsis Criteria

Abstract

The current definition for sepsis is life-threatening, acute organ dysfunction secondary to a dysregulated host response to infection. Criteria to operationalize this definition can be judged by 6 domains of usefulness (reliability; content, construct and criterion validity, measurement burden, and timeliness). The relative importance of these 6 domains depends on the intended purpose for the criteria (clinical care, basic and clinical research, surveillance, or quality improvement (QI) and audit). For example, criteria for clinical care should have high content and construct validity, timeliness, and low measurement burden to facilitate prompt care. Criteria for surveillance or QI/audit place greater emphasis on reliability across individuals and sites and lower emphasis on timeliness. Criteria for clinical trials require timeliness to ensure prompt enrollment and reasonable reliability but can tolerate high measurement burden. Basic research also tolerates high measurement burden and may not need stability over time. In an illustrative case study, we compared examples of criteria designed for clinical care, surveillance and QI/audit among 396,241 patients admitted to 12 academic and community hospitals in an integrated health system. Case rates differed 4-fold and mortality 3-fold. Predictably, clinical care criteria, which emphasized timeliness and low burden and therefore used vital signs and routine laboratory tests, had the highest case identification with lowest mortality. QI /audit criteria, which emphasized reliability and criterion validity, used discharge information and had the lowest case identification with highest mortality. Using this framework to identify the purpose and apply domains of usefulness can help with the evaluation of existing sepsis diagnostic criteria and provide a roadmap for future work.

Toward Smarter Lumping and Smarter Splitting: Rethinking Strategies for Sepsis and Acute Respiratory Distress Syndrome Clinical Trial Design

“…Although pragmatic clinical definitions promote broader recognition and implementation of first-line therapies, they may not be the optimal criteria by which to enroll patients into all RCTs (30), particularly for trials that examine therapies anticipated to work for only a subset of patients (e.g., septic patients with specific bacterial infection or patients with ARDS with diffuse alveolar damage). Clinical trials definitions require high reliability and construct validity but can also tolerate greater measurement and time burdens (31). Yet, despite the contrasting goals of clinical care and trial definitions, the majority of critical care trials over the past few decades have used clinical definitions for study entry criteria (32).…”

Evolution of Sepsis Management

“…However, it is important to note that different definitions serve different purposes (ie, bedside evaluation and management, surveillance, clinical or basic research), and each currently used and proposed definition of sepsis has utility depending on the context in which is used [7,8].…”

A Framework for the Development and Interpretation of Different Sepsis Definitions and Clinical Criteria

“…The key is to match criteria whose performance across the six domains best suits the intended purpose. In the accompanying article (19), we demonstrate the ways in which these six domains of usefulness will vary in importance depending on the intended purpose.…”