SMART Models for Sepsis Patient Stratification
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Solution Overview
Problem
Current clinical trials for sepsis treatments fail to effectively reduce septic mortality due to inclusion of nonresponsive patients, diluting the potential benefits of life-saving drugs, as existing entry criteria do not accurately identify patients who would benefit from specific therapies.
Innovation Solution
The use of Systemic Mediator-Associated Response Test (SMART) models to analyze baseline parameters and generate profiles that match patients with therapeutic agents, predicting response to treatments by comparing patient profiles with established control profiles, thereby identifying suitable subjects for clinical trials.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If traditional sepsis entry criteria (ACCP/SCCM Consensus Conference definitions) are used to enroll patients in clinical trials, then large numbers of patients can be enrolled, but the trial population includes many nonresponders whose host-inflammatory responses cannot benefit from the test compound, diluting the treatment effect and leading to false negative results
Solution Approach 1:
The patent segments the homogeneous sepsis patient population into distinct subgroups based on their host-inflammatory response profiles (e.g., high TNF-alpha responders, low TNF-alpha responders, IL-1beta responders). This segmentation allows clinical trials to enroll patients who are most likely to respond to specific mechanisms of action, thereby improving treatment efficacy detection while maintaining adequate sample sizes within each responsive subgroup
Solution Approach 2:
The patent applies local quality by matching specific patient subgroups with specific therapeutic mechanisms of action. Instead of treating all sepsis patients uniformly, the methodology identifies patients with particular inflammatory response characteristics (local quality of response) and pairs them with drugs targeting those specific pathways, thereby improving both enrollment efficiency and trial reliability
2Reliability
If broad sepsis definitions are used for patient enrollment, then clinical trials can achieve adequate statistical power, but the heterogeneity of the patient population masks the true efficacy of targeted therapies
Solution Approach 1:
The patent performs preliminary action by characterizing patients' host-inflammatory responses before randomization to treatment. Using baseline measurements of inflammatory markers and response patterns, the methodology pre-identifies which patients are most likely to respond to each mechanism of action, allowing for optimized trial design that preserves treatment effect signals while maintaining statistical power
Data Source
AI summary
Methods of identifying, monitoring and matching patients with appropriate treatments who are at risk for developing a systemic inflammatory condition using a systemic mediator-associated physiologic test profile are provided. The methods of the present invention increase the likelihood of demonstrating clinical efficacy in clinical trial datasets.