Multiple-tiered screening and second analysis
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Solution Overview
Problem
Diagnostic technologies struggle to accurately diagnose rare health conditions in large populations due to poor performance and high false positives in point-of-care tests, and invasiveness and cost in centralized testing.
Innovation Solution
A multiple-tiered analysis method involving a first screen to eliminate individuals not at risk, followed by an intra-individual analysis to account for unique baseline biological signatures, and a second analysis to detect health conditions using background-corrected methylation information from target and reference nucleic acids.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If point-of-care tests are applied to large populations, then testing coverage is improved, but diagnostic accuracy deteriorates due to high false positives and low positive predictive value
Solution Approach 1:
The diagnostic process is segmented into multiple tiers: a first screening tier using simplified molecular inverse design (SMID) tests for large populations, followed by a second analysis tier for at-risk individuals. This segmentation allows high-throughput screening while maintaining diagnostic accuracy through progressive refinement of testing complexity.
Solution Approach 2:
The first SMID screening tier performs preliminary identification of at-risk individuals before applying more complex and accurate diagnostic methods. This preliminary action filters the large population to a smaller at-risk subset, preserving overall diagnostic accuracy while maintaining high testing coverage.
2Measurement precision
If complex centralized testing is deployed for rare population testing, then diagnostic accuracy is improved, but invasiveness and cost increase
Solution Approach 1:
The testing strategy applies local quality by matching test complexity to population risk: simplified SMID tests for the general population and more complex centralized testing only for identified at-risk individuals. This ensures high diagnostic accuracy where needed while avoiding unnecessary complexity and cost for the broader population.
3Device complexity
If molecular signatures are analyzed without accounting for baseline biological variation, then analysis simplicity is maintained, but false positives increase reducing positive predictive value
Solution Approach 1:
The patent introduces an intermediary comparative analysis step where molecular signatures are evaluated relative to baseline biological variation and control samples. This intermediary process filters out false positives caused by individual biological variability while maintaining systematic analysis, thereby improving positive predictive value without excessive complexity.
Data Source
AI summary
Disclosed herein are methods, non-transitory computer readable media, systems, and kits for performing a multiple tiered analysis for identifying individuals with a health condition for monitoring, treating, and/or enrolling the individuals in a clinical trial. Specifically, the multiple tiered analysis involves a first screen, which eliminates a large proportion of individuals who are identified as not at risk for a health condition, and a subsequent second analysis which detects presence of a health condition in the remaining individuals. The second analysis includes an intra-individual analysis, which involves combining sequence information from target nucleic acids and reference nucleic acids obtained from the individual. The target nucleic acids include signatures that may be informative for determining presence or absence of the health condition and the reference nucleic acids include baseline biological signatures of the individual. Altogether, the multiple tiered analysis achieves improved performance and accurate identification of individuals with the health condition.