Multiple-Tier Screening With Intra-Individual Analysis for Rare Diagnostics
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Solution Overview
Problem
Diagnostic technologies struggle to accurately identify individuals with rare health conditions in large populations due to poor performance and invasiveness of centralized testing, while POC tests lack the necessary accuracy.
Innovation Solution
A multiple-tiered analysis method involving a first screen to eliminate non-risk individuals, 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
1Measurement precision
If complex centralized testing is deployed for rare population testing, then diagnostic accuracy can be improved, but the testing becomes invasive, expensive, and fails when applied to large patient populations
Solution Approach 1:
The diagnostic process is divided into multiple tiers: a first screening tier using simpler tests to identify at-risk individuals, followed by a second tier using more complex centralized testing only on those who screened positive. This segmentation allows complex testing to be applied efficiently to small subsets rather than large populations, reducing overall cost and invasiveness while maintaining high diagnostic accuracy.
2Productivity
If POC tests are applied to large populations, then screening efficiency is improved, but diagnostic accuracy is insufficient for rare health conditions
Solution Approach 1:
The testing strategy segments the population into two groups: those who undergo POC screening for efficiency, and those who then proceed to more accurate centralized testing for confirmation. This two-stage approach maintains high screening efficiency while ensuring diagnostic accuracy through the second-tier testing of at-risk individuals.
Solution Approach 2:
The first-tier POC test acts as an intermediary that filters the large population to identify a smaller subset of at-risk individuals. This intermediary screening step enables the subsequent use of more accurate but resource-intensive centralized testing to be applied only where necessary, balancing efficiency and accuracy.
3Quantity of substance
If centralized testing is applied to large populations, then comprehensive screening is achieved, but false positives increase and positive predictive value decreases
Solution Approach 1:
The population is segmented into screened and unscreened groups, with centralized testing applied only to those who tested positive in the first tier. This segmentation prevents the dilution effect that occurs when centralized testing is applied to entire populations, thereby maintaining high positive predictive value while still achieving comprehensive coverage of at-risk individuals.
Solution Approach 2:
A preliminary screening step is performed using POC tests before applying centralized testing. This preliminary action identifies and isolates at-risk individuals, ensuring that subsequent centralized testing is performed only on appropriate candidates, which prevents false positives from healthy individuals and maintains high positive predictive value.
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.