Search Results

The Omics Core assay is a qualitative in vitro diagnostic test that uses targeted next generation sequencing of formalin-fixed paraffinembedded tumor tissue matched with normal specimens with solid malignant neoplasms to detect tumor gene alterations in a broad multi gene panel. The test is intended to provide informations (point mutations (point mutations and deletions) and tumor mutational burden (TMB) for use by qualified health care professionals in accordance with professional guidelines, and is not conclusive or prescriptive for labeled use of any specific therapeutic product. Omics Core is a single-site assay performed at NantHealth, Inc.

The NantHealth Omics Core assay is a custom targeted whole exome sequencing platform, utilizing solution-phase exon capture and sequencing, to report somatic alterations (point mutations, small insertions and deletions) in 468 genes and sequencing of 19,396 protein-coding genes (whole exome) to determine overall tumor mutation burden in tumor specimens. Genomic DNA is extracted from both a tumor and a patient-matched normal control sample. Sequence libraries are prepared through a series of enzymatic steps including shearing of double-stranded DNA, end repair, A-base addition, ligation of barcoded sequence adaptors, and low cycle PCR amplification. Single barcoded sequence libraries are captured using the biotinylated probes. Captured DNA fragments are then pooled and sequenced on an Illumina NovaSeq 6000 as paired-end reads. Sequence reads are then aligned to the reference human genome. Somatic alterations are identified in the tumor DNA by direct comparison to the matched normal DNA.

The Omics Core assay, a targeted next-generation sequencing test, was evaluated to determine its performance specifications, including precision, analytical sensitivity (Limit of Detection), and accuracy.

Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly list "acceptance criteria" as a separate column with specific numerical thresholds for each performance metric. Instead, it presents "Performance Specifications" as the expected or demonstrated performance of the device based on the studies. The reported device performance is then detailed under each characteristic.

Table: Omics Core Performance Specifications and Reported Device Performance

2. Sample Size Used for the Test Set and the Data Provenance:

• Precision Studies:
  • Panel-Wide Reproducibility, Per Specimen, and TMB Precision: 12 FFPE clinical tumor samples and 1 commercial cell line.
  • Well-Characterized Reference Material: 1 well-characterized sample.
• Analytical Sensitivity (LoD) Studies:
  • SNVs and Indels: 13 FFPE clinical samples.
  • TMB: 10 FFPE tumor specimens.
• Accuracy – Comparison to Orthogonal Method: 401 FFPE tumor samples.
• Accuracy – Supplemental Method Comparisons Study for Wildtype Calls: 220 positive mutations and 12,612 wildtype calls (implied as part of a larger dataset from clinical samples, likely from the accuracy comparison or other internal data).

Data Provenance: The document does not explicitly state the country of origin for the clinical samples. They are referred to as "FFPE clinical tumor samples" and "clinical specimens," suggesting they are real-world patient samples. The studies are described as "Performance Data" supporting the submission, implying they are retrospective analyses of collected samples.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts:

The document does not provide information on the number of experts or their qualifications specifically for establishing the ground truth for the test set.

For the predicate device (MSK-IMPACT), it mentions "Classification criteria were developed by MSK using the in-house OncoKB database. OncoKB undergoes periodic updates through the review of new information by a panel of experts."

For the subject device (Omics Core), it states: "Classification criteria were developed by NantHealth, Inc. NantHealth periodically updates Omics Core through the review of new information available."

However, this refers to the curation and classification of clinical evidence and mutations, not the establishment of ground truth for the analytical performance studies (precision, accuracy, LoD). The ground truth for the analytical studies appears to be based on:

• Orthogonal methods: For accuracy studies, results from an alternative, validated method are used for comparison.
• Known characteristics: For precision with a well-characterized reference material, the known variants in that material serve as ground truth.
• Internal consistency/comparison: For precision and LoD studies, the consistency and detection rates across replicates and dilutions are evaluated.

4. Adjudication Method for the Test Set:

The document does not describe an explicit adjudication method (e.g., 2+1, 3+1) for establishing ground truth for the test set. The nature of the studies (NGS analytical performance) relies on comparison to orthogonal methods or predefined characteristics of reference materials rather than expert review of images or clinical reports that might require such adjudication.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:

No, an MRMC comparative effectiveness study was not done. This device is a diagnostic test (Next Generation Sequencing based tumor profiling test), not an imaging AI device that would typically involve human "readers" and MRMC studies. The "performance data" relate to the analytical validity of the test (how accurately it detects gene alterations and TMB), not its impact on human clinical decision-making or interpretation.

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done:

The studies described primarily represent the standalone (algorithm and laboratory process only) performance of the Omics Core assay in detecting mutations and TMB. The "human-in-the-loop" aspect is implicitly through laboratory technicians performing the test and the medical director signing off on reports, but the reported performance metrics (precision, accuracy, LoD) assess the analytical capabilities of the system itself, independent of immediate human interpretive assistance on a case-by-case basis during the core analysis.

7. The Type of Ground Truth Used:

The ground truth used in the performance studies varied:

• Orthogonal Method: For accuracy studies of SNVs, indels, and TMB, the Omics Core results were compared to results obtained from an "orthogonal method." The specific method is not detailed, but it implies a different, validated technology used to confirm the presence and characteristics of mutations.
• Well-Characterized Reference Material: For precision, a "well-characterized sample" (likely with known variant profiles) was used.
• Clinical Samples: For precision and LoD, findings from "FFPE clinical tumor samples" and "commercial cell line" were used, with the "truth" being established through consistent detection across replicates or successful reliable calling at certain frequencies. This implies that for clinical samples, the ground truth was based on the consensus of repeated measurements or the expectation of what should be detected in those samples.

The document does not mention pathology re-read, expert consensus, or outcomes data as direct ground truth for these analytical performance studies.

8. The Sample Size for the Training Set:

The document does not specify the sample size for the training set. The provided performance data relates to verification and validation studies (test set), not the development or training of the assay's bioinformatics component. The "Omics Core software" is mentioned as part of the bioinformatics workflow, but details on how its underlying algorithms (for variant calling, TMB calculation) were trained are not provided.

9. How the Ground Truth for the Training Set Was Established:

As the document does not specify a training set sample size, it also does not explain how the ground truth for a training set was established. The process description focuses on the analytical performance of the finished device. It mentions "Assay optimization" and that "High analytical specificity is maintained by paired tumor/matched normal sequencing, and established during assay optimization," suggesting that internal data or processes were used during development, but without details on ground truth establishment for such activities.

Ask a specific question about this device