The MOLDX DEX REGISTRY has 5 variations of breast cancer tests for Natera Signatera. It's hard to wrap your head around them. I "dumped" the text into Chat GPT and asked it to re organize the results.
I have not proofed or edited the result.
In a recent post, Amal Thommil of Decibio commented on Natera interest in WGS for MRD.
First I show one screen grab of the MolDx source, then, I show the Chat GPT output.
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| one screen grab (input) |
1. Test Comparison Table (Auto Table)
2. Key Differentiators
Source of Mutation Identification:
- Tests #1 and #2: Utilize pre-existing CGP sequencing data, streamlining assay design.
- Tests #4 and #5: Perform new whole exome/genome sequencing on tumor and normal DNA, providing a more comprehensive mutation analysis.
Testing Coverage:
- Single Test vs. Serial Monitoring:
- Tests #1 and #4: Cover initial plasma analysis only.
- Tests #2, #3, and #5: Include series bundles for longitudinal monitoring.
- Single Test vs. Serial Monitoring:
Cost Implications:
- Tests that include tumor/normal sequencing (Tests #4 and #5) are significantly more expensive due to the complexity and depth of the upfront sequencing process.
- The series bundle adds value for long-term monitoring but increases cost (e.g., $2,902 for Test #2 vs. $2,098 for Test #1).
3. Clinical and Coverage Insights for MolDx
Test-Specific Strengths:
- CGP-Based Tests (#1 and #2): Leverage existing sequencing data, reducing cost and time while maintaining a high level of sensitivity for ctDNA detection.
- Tumor/Normal-Based Tests (#4 and #5): Offer more comprehensive and personalized insights by comparing tumor DNA to normal DNA, which can detect additional somatic mutations.
Utility of Serial Plasma Testing:
- Tests with plasma series bundles (#2, #3, and #5) allow for dynamic monitoring of ctDNA, which is crucial for tracking tumor burden and therapy response over time.
Cost Variability:
- The cost structure aligns with the complexity of the test. Tests requiring upfront tumor/normal sequencing and serial monitoring are the most expensive (Test #5: $4,672).
4. Considerations for MolDx Review
Reproducibility and Workflow Clarity:
- Clearly differentiate when pre-existing CGP data is sufficient (Tests #1 and #2) versus when fresh tumor/normal sequencing is necessary (Tests #4 and #5).
- Justify the added value of whole exome/genome sequencing in Tumor/Normal-based tests despite higher costs.
Clinical Utility Across Tests:
- Emphasize how serial monitoring improves actionable insights compared to one-time plasma testing.
- Demonstrate consistency of ctDNA detection across breast cancer subtypes and treatment stages.
Patient Access:
- The tiered pricing structure ensures accessibility to MRD testing across patient demographics, from minimal-cost options (Test #3: $1,588) to comprehensive packages (Test #5: $4,672).
5. Simplified Summary of Applications
- For Initial Detection: Tests #1 and #4 provide baseline MRD insights.
- For Longitudinal Monitoring: Tests #2, #3, and #5 track ctDNA dynamics over time.
- For Comprehensive Mutation Analysis: Tests #4 and #5 offer the most detailed mutation profiling by sequencing both tumor and normal DNA.
This breakdown should make it easier to contextualize the significance of these tests and their appeal to MolDx evaluators. Let me know if you'd like further refinements or graphical comparisons!
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Chat GPT did a very poor job of imputing cost (ver 4o).
However, with some coaxing I got these obvious conclusions from it (they are basic arithmetic from the data given, though it takes a bit to see it):
Summary of Key Costs
- Plasma Series (Serial Testing): $1588 (from Test #3).
- Bespoke Assay Design from CGP Data: $1314 (Test #2 - Test #3).
- WGS-Based Tumor/Normal Sequencing: $1770 (Test #5 - Test #2).
These insights break down the components clearly and align with the structure of MolDx's coverage for these tests. Let me know if you'd like further refinements!
