SMART Biomarker Profiling for Sepsis Patient Stratification
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Solution Overview
Problem
Current clinical trials for sepsis have failed to reduce septic mortality due to inappropriate patient selection criteria, diluting the effectiveness of potential life-saving drugs, as existing entry criteria do not accurately identify patients who would benefit from specific therapeutic agents.
Innovation Solution
A system that uses a non-transitory computer-readable medium to generate a systemic mediator-associated response test (SMART) profile from patient data, including demographic, physiologic, and gene expression variables, to predict the outcome of therapeutic agents and identify suitable patients for clinical trials, thereby optimizing treatment efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If traditional ACCP/SCCM Consensus Conference entry criteria are used for sepsis clinical trials, then large numbers of patients can be enrolled, but the true target population for each sepsis drug is diluted and effectiveness is lost
Solution Approach 1:
The patent segments the homogeneous sepsis patient population into distinct subpopulations based on their inflammatory response patterns. By using biomarker profiles (such as cytokine levels, acute phase reactants, and other inflammatory mediators) to stratify patients, the system creates segmented groups that are more likely to respond to specific therapeutic agents. This segmentation allows clinical trials to enroll sufficient numbers of patients while maintaining precision in patient selection, resolving the contradiction between quantity and measurement precision.
2Reliability
If broad entry criteria are used to maximize trial enrollment, then statistical power is improved, but potentially life-saving drugs are deemed ineffective due to inclusion of nonresponders
Solution Approach 1:
The patent applies preliminary action by using biomarker-based stratification to pre-identify patients who are likely to respond to a specific therapeutic agent before they are enrolled in the clinical trial. This preliminary classification allows the trial to enroll a focused cohort of responsive patients, thereby maintaining statistical power while ensuring that the drug's efficacy can be demonstrated in the appropriate population. The preliminary biomarker assessment prevents the dilution effect that occurs when nonresponders are included, thus resolving the contradiction between reliability and productivity.
3Ease of operation
If traditional clinical definitions of sepsis are used, then trials can be conducted with available data, but the host-inflammatory responses of enrolled patients are unable to benefit from test compounds
Solution Approach 1:
The patent changes the parameters used for patient selection from broad clinical definitions of sepsis to specific biomarker profiles that characterize different inflammatory response patterns. By measuring and analyzing levels of specific cytokines, acute phase reactants, and other inflammatory mediators, the system transforms the selection criteria into more precise parameters that predict response to therapeutic agents. This parameter change maintains ease of operation through standardized biomarker assays while dramatically improving treatment effectiveness by matching patients to appropriate therapies based on their inflammatory phenotype.
Data Source
AI summary
A system for identifying, monitoring and matching patients with appropriate treatments using a systemic mediator-associated physiologic test profile are provided. The system of the present invention increases the likelihood of demonstrating clinical efficacy in clinical trial datasets.