(121 days)
The Pathwork® Tissue of Origin Test is intended to measure the degree of similarity between the RNA expression pattern in a patient's fresh-frozen tumor and the RNA expression patterns in a database of tumor samples (poorly differentiated, undifferentiated and metastatic cases) that were diagnosed according to then current clinical and pathological practice. The database contains examples of RNA expression patterns for fifteen common malignant tumor types: bladder, breast, colorectal, gastric, hepatocellular, kidney, non-small cell lung, ovarian, pancreatic, prostate, and thyroid carcinomas, melanoma, testicular germ cell tumor, non-Hodgkins lymphoma (not otherwise specified), and soft tissue sarcoma (not otherwise specified). The Pathwork® Tissue of Origin Test result is intended for use in the context of the patient's clinical history and other diagnostic tests evaluated by a qualified clinician.
Limitations: The Pathwork Tissue of Origin Test is not intended to establish the origin of tumors that cannot be diagnosed according to current clinical and pathological practice. (e.g. carcinoma of unknown primary). It is not intended to subclassify or modify the classification of tumors that can be diagnosed by current clinical and pathological practice, nor to predict disease course or survival or treatment efficacy, nor to distinguish primary from metastatic tumor. Tumor types not in the Pathwork Tissue of Origin Test database may have RNA expression patterns that are similar to RNA expression patterns in tumor types in the database, leading to indeterminate results or misclassifications,
The Pathwork® Tissue of Origin Test is a microarray and analytics "kit" that quantifies the similarity of tumor specimens to 15 cancer types representing 60 morphologies. Frozen biopsy specimens are processed by the clinical laboratory as described in the User Guide. In brief, mRNA is extracted, amplified, labeled and hybridized to the Pathchip® microarray, which is then scanned using one of the instrument systems validated for use with this test. The resulting data file is transmitted via secure internet transfer protocol to the Pathwork® System Software for data quality control and analysis. Test results are available for clinical interpretation via a secure password protected website.
Components included in the kit:
Microarray: Pathchip microarrays, packaged in boxes of 5 or 10.
Tissue of Origin Test Report produced by the Pathwork System Software (by licensed agreement): The Pathwork® System Software receives data from the scanned Pathchip™ microarray and performs data quality control and analysis. The System Software then generates a Pathwork® Tissue of Origin Test Report which provides a Similarity Score for each of the 15 tissues on the test panel. The test report is accessible for clinical interpretation via a secure password protected website.
Tissue of Origin Test Reagents: Reagents for specimen processing and RNA extraction.
Here's a breakdown of the acceptance criteria and study details for the Pathwork® Tissue of Origin Test, based on the provided document:
Acceptance Criteria and Reported Device Performance
| Acceptance Criteria Category | Acceptance Criteria (Implicit) | Reported Device Performance |
|---|---|---|
| Accuracy (Positive Percent Agreement) | High Positive Percent Agreement (Specific threshold not explicitly stated but generally expected above 85-90%) | 89.4% (487/545) across all 15 tissues |
| Accuracy (Negative Percent Agreement) | High Negative Percent Agreement (Specific threshold not explicitly stated but generally expected above 95%) | 99.6% (507/509) across all 15 tissues |
| Precision (Site-to-site concordance) | High inter-site concordance (Specific threshold not explicitly stated but generally expected above 90%) | Approximately 93% overall site-to-site concordance |
| Interfering Substances | No significant impact on performance from common interfering substances in biopsy specimens (e.g., adipose tissue, fibrous tissue, necrotic tissue). Adequate performance with pancreas-related specimens despite known RNase levels. | No effect from high levels of adipose tissue, fibrous tissue, or necrotic tissue (up to 20% of biopsy specimen). Adequate performance with pancreas-related specimens, though performance is lower due to elevated RNases. |
Study Information
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Sample size used for the test set and the data provenance:
- Sample Size: 545 frozen specimens.
- Data Provenance: Not explicitly stated, but the study was performed at "four laboratory sites," implying multi-center data collection. It is likely retrospective as the samples were "diagnosed according to then current clinical and pathological practice" and stored as "frozen specimens."
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Number of Experts: Not specified.
- Qualifications: Ground truth was established by "the available diagnosis" based on "current clinical and pathological practice." This suggests diagnosis by qualified pathologists and clinicians, but specific numbers and their years of experience are not detailed.
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Adjudication method for the test set:
- Not explicitly stated. The document refers to "the available diagnosis," indicating that the clinical diagnoses were used as the reference standard without mentioning an adjudication process for discrepancies in the test set.
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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 MRMC comparative effectiveness study was done or reported in this document. The study focuses purely on the device's standalone performance against a diagnostic ground truth.
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If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, a standalone study was performed. The reported accuracy (positive and negative percent agreement) refers to the performance of the Pathwork® Tissue of Origin Test itself in identifying the tissue of origin. The device generates "Similarity Scores" and a "Test Report" for clinical interpretation, but the performance metrics provided are for the algorithm's output.
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The type of ground truth used:
- Clinical and Pathological Diagnosis: The ground truth for the test set was established based on "the available diagnosis" from "current clinical and pathological practice." This refers to established clinical and histopathological diagnoses for the tumor samples.
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The sample size for the training set:
- The document states that the test "quantifies the similarity of tumor specimens to 15 cancer types representing 60 morphologies" against "RNA expression patterns in a database of tumor samples." However, it does not explicitly state the sample size of this database used for training the algorithm. It only mentions the database contains examples of RNA expression patterns.
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How the ground truth for the training set was established:
- The ground truth for the samples in the database (which would have been used for training) was established by samples "diagnosed according to then current clinical and pathological practice." This implies standard clinical and pathological evaluations of the source tumor samples in the database.
§ 862.3100 Amphetamine test system.
(a)
Identification. An amphetamine test system is a device intended to measure amphetamine, a central nervous system stimulating drug, in plasma and urine. Measurements obtained by this device are used in the diagnosis and treatment of amphetamine use or overdose and in monitoring levels of amphetamine to ensure appropriate therapy.(b)
Classification. Class II (special controls). An amphetamine test system is not exempt if it is intended for any use other than employment or insurance testing or is intended for Federal drug testing programs. The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9, provided the test system is intended for employment and insurance testing and includes a statement in the labeling that the device is intended solely for use in employment and insurance testing, and does not include devices intended for Federal drug testing programs (e.g., programs run by the Substance Abuse and Mental Health Services Administration (SAMHSA), the Department of Transportation (DOT), and the U.S. military).