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The Verigene System is a bench-top molecular diagnostics workstation that automates the analysis and detection of nucleic acids using gold nanoparticle probe technology.

The Verigene F5 Nucleic Acid Test is Indicated as an aid to diagnosis in the evaluation of patients with suspected thrombophilia. The test is an in vitro diagnostic for the detection and genotyping of a single-point mutation (G to A at position 1691; also known as Factor V Leiden) of the human Factor V gene (F5; Coagulation Factor V gene), from Isolated genomic DNA obtained from whole blood samples. The test is intended to be used on the Verigene System.

The Verigene F2 Nucleic Acid Test is indicated as an aid to diagnosis in the evaluation of patients with suspected thrombophilia. The test is an in vitro diagnostic for the detection and genotyping of a single-point mutation (G to A at position 20210) of the human Factor II gene (F2; prothrombin gene), from isolated genomic DNA obtained from whole blood samples. The test is intended to be used on the Verigene System.

The Verigene MTHFR Nucleic Acid Test is indicated as an aid to diagnosis in the evaluation of patients with suspected thrombophilia and elevated levels of homocysteine or altered folate metabolism. The test is an in vitro diagnostic for the detection and genotyping of a single-point mutation (C to T at position 677) of the human 5,10 methylenetetrahydrofolate reductase gene (MTHFR), from isolated genomic DNA obtalned from whole blood samples. The test is intended to be used on the Verigene System.

The Verigene System is an in vitro diagnostic device for processing and genotyping multiple genes in a DNA sample. The Verigene System consists of two instruments, the Verigene Processor and the Verigene Reader, and utilizes single-use, disposable Test Cartridges to process and genotype multiple genes in a DNA sample in approximately 1½ hours. Clinicians use one or more of the three genes (F5, F2, MTHFR) and their associated single nucleotide polymorphisms (SNPs) to help diagnose patients' hereditary contributory factors in forming blood clots (thrombi). On the Verigene System, hypercoagulation testing can include one or more of three genotypes that are associated with hypercoagulation (i.e., thrombophilia). These tests use extracted and purified DNA, mixed with hybridization buffer, loaded into the sample well of the Test Cartridge. The genotyping process occurs with a hybridization of the target analyte to a synthetic gene-specific oligonucleotide capture strand on the Test Cartridge's substrate. A synthetic mediator target-specific oligonucleotide is included with the test-specific sample buffer to form a hybridization "sandwich" with the gene sequence of interest. Washing steps following the target hybridization remove the unbound DNA from the hybridization chamber. A probe, composed of a gold nanoparticle with covalently bound oligonucleotides complementary to a sequence on the intermediate oligonucleotide, is introduced after the target wash. After the probe hybridization is completed, a series of washing steps remove the unbound probe from the hybridization chamber. A two-part signal enhancement reagent is added to the hybridization chamber and reacts with the gold nanoparticle to amplify the signal for the Verigene Reader scanning and analysis. Upon completion of the genotyping process, the user removes the Test Cartridge from the Verigene Processor which is now ready for the next test. Once the reagent portion of the Test Cartridge is removed by the user, the substrate is inserted into the Verigene Reader. The Verigene Reader illuminates the signal-enhanced nanoparticles specifically bound to either the wild type or mutant captures for the gene. A photosensor reads the relative brightness of each spot and the Verigene Reader outputs a result based on relative levels of brightness of the wild type to mutant signals.

Here's a summary of the acceptance criteria and study information for the Nanosphere Verigene System and its associated nucleic acid tests, based on the provided text:

Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied through the reported performance for diagnostic sensitivity and specificity, and the call rate. While explicit numerical acceptance criteria for these metrics aren't stated as "acceptance criteria," the reported 100% diagnostic sensitivity and specificity, and the high call rates, indicate successful performance for a device seeking substantial equivalence.

Study Details

1. Sample sizes used for the test set and the data provenance:

   • Reproducibility Study #1:
     • F5: 118 samples (Site 1, Operators A & B), 60 samples (Site 2, Operators C & D), 58 samples (Site 3, Operator E), 59 samples (Site 3, Operator F). Total = 295 samples. (Note: The "Correct Calls (%)" sums slightly differently across operators for F5, F2, MTHFR, so this is derived from the "Total Calls" which is 118 for Site 1, 60 for Site 2, 58 for Operator E Site 3, and 59 for Operator F Site 3. The footnote clarifies that 10 cartridges failed to run, meaning the total tests attempted were higher.)
     • F2: Similar sample numbers as F5 for each site and operator.
     • MTHFR: Similar sample numbers as F5 for each site and operator.
     • Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective).
   • Diagnostic Sensitivity/Specificity & Call Rate: Values are based on a total of 287 calls made (for Call Rate), implying a test set of at least 287 samples when considering successful calls. The specific number of samples for diagnostic sensitivity and specificity calculation is presented with 95% confidence intervals, but the raw count is not provided (e.g., "out of X positive samples" or "out of Y negative samples").
   • Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective).

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

   • The document does not specify the number of experts or their qualifications used to establish the ground truth for the test set. The nature of the device (genotyping) suggests the ground truth would likely be established by a reference genetic test or sequencing.

3. Adjudication method (e.g. 2+1, 3+1, none) for the test set:

   • The document does not describe any adjudication method.

4. 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. This device is a diagnostic test for genetic mutations, not an imaging device requiring human reader interpretation, nor does it involve AI assistance for human readers.

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

   • Yes, a standalone performance study was done. The performance characteristics (reproducibility, analytical sensitivity, call rate, diagnostic sensitivity, diagnostic specificity) are for the Verigene System itself, operating as an automated in vitro diagnostic device. Human operators are involved in sample preparation and loading, but the genotyping analysis and detection are automated by the system.

6. The type of ground truth used (expert concensus, pathology, outcomes data, etc):

   • The document does not explicitly state the method for establishing ground truth, but for genetic tests, the ground truth is typically established by orthogonal genetic testing methods such as DNA sequencing or a clinically validated reference method for detecting the specific gene mutations (e.g., PCR-based assays from a reputable lab). The predicate devices are also nucleic acid test kits, supporting this assumption.

7. The sample size for the training set:

   • The document does not specify a training set or its sample size. This type of device relies on established probe chemistry and detection algorithms based on biophysical principles, rather than machine learning models that require a distinct training phase.

8. How the ground truth for the training set was established:

   • As no training set is described, there's no information on how its ground truth would have been established.

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