The Genomadix Cube CYP2C19 System is a qualitative in vitro diagnostic test for the identification of a patient's CYP2C19 *2, *3, and *17 genotypes determined from genomic DNA obtained from a buccal swab sample.

The Genomadix Cube CYP2C19 System can be used to aid clinicians in determining therapeutic strategy for therapeutics that are metabolized by the cytochrome P450 2C19 gene product, specifically *2, *3, and *17 alleles. This test is not intended to be used to predict drug response or non-response.

The Genomadix Cube CYP2C19 Test Kit is indicated for use with the Genomadix Cube CYP2C19 Platform.

The Genomadix Cube CYP2C19 System is a sample-to-result DNA testing system with integrated DNA extraction and amplification. Genotypes are determined using Polymerase Chain Reaction (PCR) and fluorescent probe detection. The Genomadix Cube CYP2C19 System is comprised of the Genomadix Cube CYP2C19 Platform (Genomadix Cube, computer, and barcode scanner) and the Genomadix Cube CYP2C19 Test Kit (swabs and cartridges). The test is run on the Genomadix Cube CYP2C19 Platform.

The Genomadix Cube is a thermal cycling instrument that automatically integrates extraction of DNA from the buccal sample, PCR amplification, fluorescence-based detection of CYP2C19 alleles, and genotype calling.

Acceptance Criteria and Study Details for Genomadix Cube CYP2C19 System

The Genomadix Cube CYP2C19 System is a qualitative in vitro diagnostic test for the identification of a patient's CYP2C19 *2, *3, and *17 genotypes from genomic DNA obtained from a buccal swab sample.

The acceptance criteria for the device performance are not explicitly stated as distinct pass/fail thresholds in the provided text. However, the study results demonstrate the device's accuracy and reproducibility, implying that the reported performance metrics serve as the de facto acceptance criteria. The primary performance metric appears to be the "correct call rate."

1. Table of Acceptance Criteria and Reported Device Performance

2. Sample Sizes and Data Provenance

Reproducibility Study:

• Test Set Sample Size: 8 individuals (buccal samples) across 3 sites. A total of 960 tests were performed across the 3 sites (8 subjects x 2 operators x 2 sessions x 2 replicates x 5 days).
• Data Provenance: Not explicitly stated, but the study was conducted at 3 sites, implying a multi-center study likely within the country of the applicant (Genomadix Inc.). The study involved prospective sample collection from individuals for the purpose of the study.

Analytical Specificity/Interference Study:

• Test Set Sample Size: 16 samples for each of the 14 potential interfering substances, totaling 224 samples. These were buccal swab samples from individuals with specific genotypes (4 replicates of each genotype tested).
• Data Provenance: Not explicitly stated, but likely prospective collection for the study.

Detection Limit Study:

• Test Set Sample Size:
  • Swabbing conditions (LLoD, IFU, ULoD): A total of 208 tests in the first pass across various swabbing conditions.
  • Expected DNA concentration: 140 samples for low concentration (20 replicates from 7 individuals) and 21 samples for high concentration (3 replicates from 7 individuals).
• Data Provenance: Not explicitly stated, but likely prospective collection for the study.

Carry-Over Study:

• Test Set Sample Size: 122 samples (61 *1/*1 genotypes alternated with 61 non-*1/*1 genotypes).
• Data Provenance: Not explicitly stated.

Method Comparison Study:

• Test Set Sample Size: 444 unique patient samples initially collected. 11 samples were excluded for low quality, resulting in 433 samples included in the final analysis.
• Data Provenance: Not explicitly stated, but samples were collected from unique patients for this study, implying prospective collection. The multi-site nature (3 sites) suggests a broader data collection if applicable.

3. Number of Experts for Ground Truth and Qualifications

For Reproducibility, Analytical Specificity/Interference, Detection Limit, and Method Comparison Studies:

• Number of Experts: Not explicitly stated in terms of "experts establishing ground truth."
• Qualifications of Experts: The ground truth for these studies was established by bi-directional sequencing. This is a highly accurate molecular method and itself serves as the "gold standard" for genotype confirmation. The performance of the sequencing would be overseen by qualified laboratory personnel, though details on their specific qualifications (e.g., molecular geneticists, clinical laboratory directors) are not provided.

4. Adjudication Method for the Test Set

The adjudication method used throughout the performance studies (reproducibility, interference, detection limit, method comparison) involved a "second pass" testing for inconclusive results:

• "If an inconclusive result was obtained on the first set of samples, the second set of samples from the same patient were used for a second pass test."
• This indicates a repeat testing adjudication for inconclusive results. There is no mention of a formal expert consensus (e.g., 2+1, 3+1) for resolving discrepancies between the device and the ground truth. The ground truth (bi-directional sequencing) is considered definitive.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not explicitly described or performed. The device is an automated genotyping system, so the concept of human readers "improving with AI vs. without AI assistance" does not directly apply in the traditional sense of image interpretation or complex diagnostic decision-making. The study focuses on the device's accuracy against a molecular gold standard.

6. Standalone Performance Study

Yes, the studies described (Reproducibility, Analytical Specificity/Interference, Detection Limit, Carry-Over, and Method Comparison) represent standalone performance of the algorithm/device. The device processes samples and generates genotype calls without direct human intervention in the interpretation of raw signal data. The "correct call rate" is a measure of the algorithm's performance alone against the established ground truth.

7. Type of Ground Truth Used

The primary type of ground truth used across all reported studies (reproducibility, interference, detection limit, and method comparison) was bi-directional sequencing. This is a gold standard molecular technique for confirming DNA sequences and, consequently, genotypes.

8. Sample Size for the Training Set

The document does not provide details on the sample size used for the training set. This is common for this type of medical device submission, as the focus is on the analytical validation of the finished device. The underlying algorithms for PCR-based fluorescent probe detection are based on well-established biochemical principles rather than statistical machine learning models that require explicit training sets.

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

As no explicit "training set" and associated ground truth establishment is described for a machine learning model, this information is not applicable in the context of the provided document. The device's operation relies on established principles of molecular diagnostics (PCR, fluorescent probe detection) and programmed thresholds for signal analysis, rather than an trained artificial intelligence model in the contemporary sense.

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The TruDiagnosis® System is an in vitro diagnostic device intended for processing and genotyping multiple genetic variants in a DNA sample utilizing on-slide PCR gel-drop microarray technology. The TruDiagnosis® System consists of the TruDx® 2000 Imager, the TruArray® Warfarin Sensitivity Test Kit, and the ProFlex™ PCR System using the ProFlex™ 2x Flat Sample Block.

The TruDx® 2000 Imager is an instrument intended for processing and genotyping multiple genetic variants in a DNA sample utilizing on-slide PCR gel-drop microarray technology.

The TruArray® Warfarin Sensitivity Test Kit is an in vitro diagnostic test for the detection and genotyping of the 2C92, 2C93 alleles of the cytochrome P450 (CYP450) 2C9 gene locus and Vitamin K epoxide reductase CL, VKORCI, gene promoter polymorphism (-1639) from genomic DNA of human saliva samples collected using the Oragene® Dx Device (OGD-500) as an aid in the identification of patients at risk for increased warfarin sensitivity. The TruArray® Warfarin Sensitivity Test Kit is a qualitative assay for use in clinical laboratories upon prescription by the attending physician.

The TruDiagnosis® System is an in vitro diagnostic device intended for processing and genotyping multiple genes in a DNA sample utilizing on-slide Polymerase Chain Reaction (PCR) gel-drop microarray technology. The TruDiagnosis® System consists of the:

• Hardware: TruDx® 2000 Imager ●
• Software: TruSpot™ Software ●
• . Test Kit: TruArray® Warfarin Sensitivity Test Kit
  • TruArray® Test Slide o
  • o TruPlex™ reagents
• Thermal Cycler: ProFlex™ PCR System using the ProFlex™ 2x Flat Sample Block ●

Hardware: Akonni's microarray imager (TruDx®2000) is an instrument that consists of a highintensity green light emitting diode (LED), custom optics, and a digital grayscale camera.

• . The purpose of the TruDx® 2000 Imager is to capture a fluorescence image of the microarray after completing the test.
• The user inserts the TruArray® Test Slide into the TruDx® 2000 Imager and follows . the on-screen prompts. The resulting microarray image is automatically analyzed and reported with the TruSpot™ Software.

Software: Akonni's TruSpot™ Software, integrated within the imager, locates and segments each fluorescently labeled microarray Gel-Element and reports signal-to-noise ratios (SNR). Assay results interpreted by TruSpot™ Software program are assigned a genotype and presented to the end user in a report format.

Test Kit: The TruArray® Warfarin Sensitivity Test Kit includes consumables and reagents necessary to perform multiplex on-slide PCR amplification, and fluorogenic target-specific microarray-based hybridization. Specifically:

• The TruArray® Test Slide (loaded with target DNA) undergoes thermal cycling via . asymmetric amplification to enrich single stranded fluorescently labeled complimentary strands to capture probes printed on the microarray (asymmetric PCR and allele specific hybridization occur in the same chamber). After hybridization, arrays are washed and dried, and the user then inserts the microarray into the TruDx® 2000 Imager and follows the on-screen prompts.

The warfarin assay performed with the test kit is an in vitro diagnostic test for the detection and genotyping of the 2C92, 2C93 alleles of the cytochrome P450 (CYP450) 2C9 gene locus and Vitamin K epoxied reductase C1, VKORC1 3673, gene promotor polymorphism (-1639) mutations from genomic DNA of human saliva samples collected using the Oragene® Dx OGD-500 Device (K110701).

Thermal Cycler: The ProFlex™ PCR System with the ProFlex™ 2x Flat Sample Block, a component of the TruDiagnosis System, is an end-point thermal cycler, specifically designed for the amplification of nucleic acids using the Polymerase Chain Reaction (PCR) process. The user interface includes a touchscreen with a graphical display that shows the time, status, and temperature for each run. A touchscreen keypad allows you to enter information into fields on the display screen.

Here's an analysis of the acceptance criteria and the studies that prove TruDiagnosis® System meets them:

1. Table of Acceptance Criteria and Reported Device Performance

Based on the provided document, the acceptance criteria are not explicitly stated as distinct pass/fail thresholds in simple terms. Instead, the studies demonstrate the device's performance, aiming for high "Correct Call Rate" and agreement with Sanger sequencing, especially after addressing "No Calls". A reasonable interpretation of the implicit acceptance criteria, based on the studies, would be a high percentage of accurate genotype calls and 100% concordance with the reference method (Sanger sequencing) upon resolution of initial "No Calls".

• 125 ng: 98.4% Correct Call Rate (96.8% LCB)
• 25 ng: 98.3% Correct Call Rate (96.7% LCB)
• 2.5 ng: 94.4% Correct Call Rate (92.0% LCB)
• 0.25 ng: 64.7% Correct Call Rate (60.4% LCB)
  Final Result (after repeating No Calls):
• 125 ng, 25 ng, 2.5 ng: 100.0% Correct Call Rate (99.2% LCB or higher)
• 0.25 ng: 63.9% Correct Call Rate (59.6% LCB) - Incorrect calls were not repeated at this concentration. |
  | Method Comparison | 100% agreement with bi-directional DNA sequencing. | First Pass Calls (Overall): 98.7% Correct Call Rate (97.0% LCB).
  Final Result (after repeating No Calls): 99.7% Correct Call Rate (98.4% LCB). "All 3 No Calls were resolved upon the second repeat runs. The Final Results yielded 100% agreement between the TruArray® Warfarin Sensitivity Test Kit results and bi-directional DNA sequencing." (One incorrect call was identified as a sample mix-up, and not re-run). |
  | Endogenous Interference | 100% agreement with bi-directional DNA sequencing. | Final Results (after repeating No Calls): 100.0% agreement between the TruArray® Warfarin Sensitivity Test Kit results and bi-directional DNA sequencing for all test substances, demonstrating no effect of any interfering substances on genotyping. |
  | Exogenous Interference | 100% agreement with bi-directional DNA sequencing. | Final Results (after repeating No Calls): 100.0% agreement between the TruArray® Warfarin Sensitivity Test Kit results and bi-directional DNA sequencing. |
  | Reproducibility | 100% correct call rate across sites, operators, and lots after repeating No Calls. | First Pass Results (Overall): 84.2% (by sample genotype), 85.8% (by SNPs across all loci).
  Final Results (after repeating No Calls): 100.0% Correct Call Rate across all sample genotypes, sites, operators, and lots (95.1% LCB or higher, 99.2% overall LCB for genotypes, 99.7% overall LCB for SNPs). |

2. Sample Sizes and Data Provenance for Test Set

• Limit of Detection Study:

  • Sample Size: 3 genomic DNA samples (Donors 1, 2, 3), tested at various concentrations with 40 replicates each (total 3 * 4 * 40 = 480 replicates for initial runs, but 362 samples were ultimately tested, implying some initial runs were repeated due to control failures, and some individual test samples were re-run).
  • Data Provenance: Genotypes for these 3 donors are provided (*1/*1, *1/*3, AA; *1/*2, *1/*3, AG; *2/*2, *1/*1, GG). The origin of these DNA samples (e.g., country) is not specified. It is a retrospective study since the DNA samples were presumably pre-collected and genotyped by Sanger sequencing.

• Method Comparison Study:

  • Sample Size: 303 unique human genomic DNA samples.
  • Data Provenance: Origin of the data (e.g., country) is not specified, but the samples were isolated from human saliva specimens. It is a retrospective study as the samples were pre-collected using the Oragene® Dx OGD-500 device, extracted, and a reference genotype established.

• Interference Studies (Endogenous and Exogenous):

  • Endogenous: 5 donors, each providing saliva samples, divided into 5 aliquots (spiked with interferents or un-spiked control). Three extractions performed on each spiked/un-spiked sample. (Total 5 donors * 5 conditions * 3 extractions = 75 samples).
  • Exogenous: 5 activity groups (Eating, Drinking, Chewing Gum, Mouth Wash, Smoking) with 5 donors each. Each donor provided 2 saliva samples (baseline and 30 min post-activity), tested in triplicate. (Total 5 groups * 5 donors * 2 timepoints * 3 replicates = 150 samples).
  • Data Provenance: Saliva samples from human donors. Origin not specified. Retrospective.

• Reproducibility Study:

  • Sample Size: Six specific saliva samples (genotypes provided in the table). Each sample was processed in triplicate by 4 operators over 5 non-consecutive days (15 tests per operator per genotype). 6 genotypes * 4 operators * 15 tests = 360 samples.
  • Data Provenance: Saliva samples from human donors. Origin not specified. Retrospective for samples, but prospective for the testing process across different sites/operators.

3. Number of Experts and Qualifications for Ground Truth

The document explicitly states that the ground truth for all performance studies (Limit of Detection, Method Comparison, Interference, and Reproducibility) was established by bi-directional Sanger sequencing. It does not mention the use of human experts or their qualifications for establishing this ground truth. Sanger sequencing is a widely accepted gold standard for DNA sequencing and thus acts as the independent reference for genotyping.

4. Adjudication Method for the Test Set

The document describes an adjudication method for "No Calls" found during the initial runs. For "No Calls," the samples were repeated (re-run). Incorrect calls, however, were generally not repeated ("Incorrect Calls were not repeated" in the LoD study footnote, and for the Method Comparison, an incorrect call was attributed to a sample mix-up and "was not re-run"). This indicates an adjudication process where "no-calls" lead to re-testing, but "incorrect calls" (when a result was given but it was wrong) are investigated for root cause and not necessarily re-run for a different result in the study context.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No MRMC comparative effectiveness study was mentioned. The device, the TruDiagnosis® System, is an in vitro diagnostic device for genotyping, which typically involves laboratory testing rather than interpretation by multiple human readers (like radiology images). Therefore, a multi-reader study is not applicable in this context.

6. Standalone Performance

Yes, a standalone performance study was done. The entire performance evaluation (Limit of Detection, Method Comparison, Interference, Reproducibility) assesses the TruDiagnosis® System (which includes the TruArray® Warfarin Sensitivity Test Kit, TruDx® 2000 Imager, and TruSpot™ Software acting together as an algorithm/system) against an independent reference method (bi-directional Sanger sequencing). This is a direct measure of the algorithm's diagnostic accuracy without human intervention in the genotype interpretation after the system generates a result.

7. Type of Ground Truth Used

The ground truth used for all studies was bi-directional Sanger sequencing.

8. Sample Size for the Training Set

The document does not provide information regarding a training set or its sample size. This is typical for a 510(k) submission where the focus is on the validation of the finished device and its performance characteristics against a predicate, rather than the development and training of the underlying algorithm. The "TruSpot™ Software" is mentioned as integrated within the imager and interpreting assay results, implying it's an algorithmic component, but details on its development or training are not included in this summary.

9. How Ground Truth for the Training Set Was Established

Since no information on a training set is provided, there is no detail on how its ground truth was established.

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The provided document is an FDA 510(k) clearance letter for a medical device called "xTAG CYP2D6 Kit V3". This type of document does not contain the detailed technical information about acceptance criteria, study methodologies, or performance data that would be necessary to answer your request.

The letter confirms that the FDA has reviewed the premarket notification and determined the device is substantially equivalent to a legally marketed predicate device. It informs the manufacturer about regulatory obligations but does not include the specifics of the performance studies.

To get the information you are looking for (acceptance criteria, study details, sample sizes, ground truth establishment, expert qualifications, etc.), you would typically need to refer to documents like:

• The 510(k) summary or 510(k) Traditional submission itself, which is often publicly available through the FDA's database.
• The device's Instruction for Use (IFU) or Product Insert, which usually contains performance data.
• Scientific publications if the study results were published in peer-reviewed journals.

Therefore, based solely on the provided document, I cannot fulfill your request for: a table of acceptance criteria, sample sizes, expert details, adjudication methods, MRMC study results, standalone performance, ground truth types, or training set details.

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The eSensor® Warfarin Sensitivity Saliva Test is an in vitro diagnostic for the detection and genotyping of the *2 and *3 alleles of the cytochrome P450 (CYP450) 2C9 gene locus and the Vitamin K epoxide reductase C1 (VKORC1) gene promoter polymorphism (-1639G>A) from genomic DNA extracted from human saliva samples collected using the Oragene® Dx and ORAcollect® Dx devices, as an aid in the identification of patients at risk for increased warfarin sensitivity.

The eSensor® XT-8 instrument is an in vitro diagnostic device intended for genotyping multiple mutations or polymorphisms in an amplified DNA sample utilizing electrochemical detection technology.

The kit consists of the eSensor® Warfarin Sensitivity Saliva Test cartridge, the eSensor® Warfarin Sensitivity Saliva Test amplification reagents (including PCR mix and DNA polymerase), the eSensor® Warfarin Sensitivity Saliva Test detection reagents (including exonuclease, probes and hybridization buffer ingredients) and the eSensor® XT-8 System. One eSensor® Warfarin Sensitivity Saliva Test Kit has sufficient materials for 24 tests.

The provided document, a 510(k) summary for the eSensor® Warfarin Sensitivity Saliva Test, details performance data primarily focused on a new specimen collection kit (ORAcollect®·Dx Device) and its impact on the existing device's performance. The study aims to demonstrate that incorporating this new collection kit does not compromise the accuracy or reliability of the Warfarin Sensitivity Saliva Test.

Here's an analysis of the acceptance criteria and study findings:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state 'acceptance criteria' in terms of specific numerical thresholds for accuracy, reproducibility, or call rates. However, the studies consistently aim for 100% agreement with the ground truth (bi-directional sequencing), and 100% correct calls with 0% incorrect calls. The "Method Comparison" section indicates an aspiration for high concordance and call rate.

2. Sample Sizes and Data Provenance

• Reproducibility (Sample-to-Sample, Lot-to-Lot, Day-to-Day, Operator-to-Operator):

  • Test set sample size: 10 donors, with 3 samples each (total 30 samples collected). These were processed by 3 operators, with genotyping data evaluated for each operator for each of the 3 SNPs. This implies 20 tests per SNP per operator (based on the "20" under "Samples Tested" for each SNP for each operator), totaling 60 tests per SNP across all operators, or 120 calls per SNP when considering all samples and operators for the "Summary of Results by Sample and Genotype" table.
  • Data Provenance: Not explicitly stated, but likely prospective and from a controlled lab environment.

• Multi-center Reproducibility:

  • Test set sample size: 30 donors. Multiple saliva samples collected from each.
  • Data Provenance: Saliva samples were collected from 3 sites. Two sites were described as "professional setting" with "supervised collections," and the third site had "unsupervised collections." One sample from each donor was transported to three independent sites for extraction. All eSensor Warfarin Sensitivity Saliva testing was conducted at Site 1. This suggests a prospective data collection design, with samples from multiple (unspecified) locations. No country of origin is mentioned.

• Method Comparison:

  • Test set sample size: 156 saliva samples.
  • Data Provenance: Not explicitly stated, but implies a prospective or retrospectively collected set of human saliva samples. No country of origin is mentioned.

• Interfering Substances (Endogenous):

  • Test set sample size: 14 donors, each providing 4 saliva samples.
  • Data Provenance: Not explicitly stated, but likely prospective, controlled lab study.

• Interfering Substances (Exogenous):

  • Test set sample size: Varied per activity, ranging from 5 to 9 donors per activity group. Each donor provided samples at two time-points (immediate and 30 minutes post-activity).
  • Data Provenance: Not explicitly stated, but likely prospective, controlled lab study.

3. Number of Experts and Qualifications for Ground Truth

The ground truth for all studies was established by bi-directional DNA sequencing. This is a laboratory-based method, not typically requiring "experts" in the sense of clinical specialists. The interpretation of sequencing results is a standard molecular biology technique. No specific number of experts or their qualifications (e.g., geneticists, molecular biologists) are mentioned for establishing the ground truth, as it's assumed to be a direct, objective measurement.

4. Adjudication Method for the Test Set

The studies used bi-directional DNA sequencing as the gold standard, not a human expert adjudication process. The agreement was calculated directly between the device's genotypes and the sequencing results. If there were discrepancies in the initial device results (e.g., initial miscalls or no-calls in the method comparison), retests were performed. For instance, in the method comparison, two miscalls were attributed to "operator error (sample mix-up) occurring during the first XT8 testing" and one remaining no-call to "an operator error at the purification step." This suggests an internal investigation and re-testing process rather than an external adjudication panel.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No Multi-Reader Multi-Case (MRMC) comparative effectiveness study was done. This device is a diagnostic test for genotyping, not an imaging device or a system requiring human interpretation with or without AI assistance. Therefore, the concept of "readers improving with AI vs. without AI" is not applicable here. The device itself performs the genotyping.

6. Standalone Performance Study

Yes, a standalone performance study was done. All the performance data described (reproducibility across operators/sites, method comparison with sequencing, and interfering substances studies) directly assesses the performance of the eSensor® Warfarin Sensitivity Saliva Test (algorithm/device only, without human-in-the-loop performance influencing the genotyping call itself, though human operators are involved in sample preparation and running the test). The percentage agreement and call rates reflect the direct output of the device compared to the ground truth.

7. Type of Ground Truth Used

The primary ground truth used for all studies was bi-directional DNA sequencing. This is a highly accurate molecular method for determining genetic sequences and polymorphisms (genotypes).

8. Sample Size for the Training Set

The document is a 510(k) summary for a labeling modification (addition of a new specimen collection kit) to an already cleared device. It primarily presents validation data for the continued performance of the device with the new collection kit. It does not mention a "training set" for the eSensor® Warfarin Sensitivity Saliva Test itself, as this device likely relies on established molecular biology principles and probes designed against known genetic targets, rather than machine learning algorithms that require extensive training data. It's a deterministic diagnostic test, not an AI model that learns from data in the way a computer vision algorithm would.

9. How Ground Truth for the Training Set Was Established

As noted above, the concept of a "training set" doesn't directly apply in the context of this device. The device's design is based on known genetic sequences and electrochemical detection rather than a machine learning model. The validation studies verify its performance against the established ground truth of bi-directional DNA sequencing.

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The xTAG® CYP2C19 Kit v3 is an in vitro diagnostic test used to simultaneously detect and identify a panel of nucleotide variants found within the highly polymorphic CYP450 2C19 gene, located on chromosome 10q24, from genomic DNA extracted from EDTA or citrate anticoagulated whole blood samples. The xTAG CYP2C19 Kit v3 is a qualitative genotyping assay which can be used as an aid to clinicians in determining therapeutic strategy for the therapeutics that are metabolized by the CYP2C19 gene product, specifically *2, *3 and *17. The kit is not indicated for stand-alone diagnostic purposes. This test is not intended to be used to predict drug response or non-response.

The xTAG® CYP2C19 Kit v3 is indicated for use with the Luminex® 100/200™ instrument or MAPGIX® with xPONENT® software systems.

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The provided text describes the 510(k) clearance for the xTAG® CYP2C19 Kit v3. While it lists the device name, regulation details, and indications for use, it does not contain any information about acceptance criteria, device performance from a study, sample sizes, expert qualifications, or ground truth establishment.

Therefore, I cannot provide the requested table and study details from the given input. The document is essentially the FDA's clearance letter and the "Indications for Use" statement, not a performance study report.

To answer your request, I would need a different document that details the device's validation study, including:

• Methods and results of performance testing.
• Specific acceptance criteria used for the study.
• The breakdown of data provenance and sample sizes.
• Details on how ground truth was established and by whom.
• Information on MRMC studies or standalone performance.

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The Spartan RX CYP2C19 System is a qualitative in vitro diagnostic test for the identification of a patient's CYP2C19 *2, *3 and *17 genotype determined from genomic DNA obtained from a buccal swab sample. For prescription use only.

Spartan RX CYP2C19 Assay - The Spartan RX CYP2C19 System is indicated for use as an aid to clinicians in determining therapeutic strategies for therapeutics that are metabolized by the Cytochrome P450 2C19 gene product, and that are specifically affected by the *2, *3, and *17 alleles. The Spartan RX CYP2C19 Assay will be run on the Spartan RX CYP2C19 Platform from the buccal sample collected with a buccal swab. The Spartan RX CYP2C19 Assay is not indicated to be used to predict drug response or non-response.

Spartan RX CYP2C19 Platform - The Spartan RX CYP2C19 System is indicated for use as an aid to clinicians in determining therapeutic strategies for therapeutics that are metabolized by the Cytochrome P450 2C19 gene product, and that are specifically affected by the *2, *3, and *17 alleles. The Spartan RX CYP2C19 Platform will be used to run the Spartan RX CYP2C19 Assay.

The Spartan RX CYP2C19 System is a sample-to-result DNA testing system that uses proprietary technology to integrate DNA extraction and amplification. Genotypes are determined using PCR and fluorescent probe detection. The Spartan RX CYP2C19 System is comprised of the Spartan RX liadrooom prable a and Spartan RX CYP2C19 Assays. The Spartan RX CYP2C19 Assays are run on the Spartan RX CYP2C19 Platform.

The Spartan RX CYP2C19 System is based on the following processes:

• Buccal swab collection i.
• ii. DNA extraction
• PCR-based amplification of the target gene lii.
• Detection of the *2, *3, and *17 alleles using fluorescent-probes iv.
• Fluorescent signal detection and analysis V.
• Genotype determination vi.

The Spartan RX CYP2C19 System integrates and automates steps ii to vi. Results are presented to the end user as genotype calls. The system also has integrated controls that monitor performance of a run and automatically inform the user of any anomalies in the instrument or reagents.

The system detects the CYP2C19 *2, *3, and *17 genotypes in separate reagent tubes. The operator collects buccal swab samples from a patient; inserts each sample into a reagent tube; and then inserts the reagent tubes into a Spartan RX Analyzer instrument.

The Spartan RX CYP2C19 System is a qualitative in vitro diagnostic test for the identification of a patient's CYP2C19 *2, *3, and *17 genotype from buccal swab samples. The system comprises the Spartan RX Platform (instrumentation) and Spartan RX CYP2C19 Assays (consumables). It integrates DNA extraction, PCR-based amplification, fluorescent probe detection, and genotype determination.

Acceptance Criteria and Reported Device Performance

Note: The acceptance criteria are implicitly inferred from the reported performance results, which consistently show very high percentages of correct calls and agreement. A lower limit of detection study indicates an acceptable first pass correct call rate of 84.6% at input levels lower than 0.1 swabs per test.

Study Details

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

   • Limit of Detection (LOD):
     • Part 1: 100 individual buccal swabs collected from 40 different individuals.
     • Part 2: 52 samples were tested per condition (5 conditions, total 260 tests), collected from *1/*1, *2/*17, *17/*17, and *2/*3 individuals.
     • Data Provenance: Not explicitly stated, but implies clinical samples possibly from Canada where the submitter is located. Retrospective or prospective is not explicitly mentioned for sample collection, but the samples were analyzed as part of a validation study.
   • Method Comparison: 327 samples tested, with 325 included in the analysis.
     • Data Provenance: Not explicitly stated, but implies clinical samples. Samples were de-identified.
   • Inter-Laboratory Reproducibility: 960 tests performed (8 individuals * 2 operators * 2 sessions * 5 days * 3 sites).
     • Data Provenance: Not explicitly stated, but implies clinical samples or samples with confirmed genotypes.
   • Reagent Lot-to-Lot Reproducibility: 107 samples (Lot 1), 106 samples (Lot 2), 107 samples (Lot 3) in the first pass testing.
     • Data Provenance: Not explicitly stated.
   • Exogenous and Endogenous Interfering Substances: 16 samples tested for each of 14 substances (total 224 tests).
     • Data Provenance: Buccal swab samples collected from *1/*1, *2/*17, *17/*17, and *2/*3 individuals where genotypes were confirmed.

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

   • The ground truth for all studies was established by bi-directional sequencing. This is a molecular biology technique, not a human expert interpretation. Geneticists or molecular biologists would be involved in performing and interpreting the sequencing results, but specific numbers and qualifications are not mentioned.

3. Adjudication method for the test set:

   • The study design employed a "second pass" re-test for samples that initially yielded "No calls." For the Method Comparison and Inter-Laboratory Reproducibility studies, if a first pass resulted in a "No call," the sample was re-tested. This serves as an internal adjudication or re-evaluation mechanism. No explicit "2+1" or "3+1" expert adjudication is described, as the ground truth is objective sequencing data.

4. Multi-reader multi-case (MRMC) comparative effectiveness study:

   • No MRMC comparative effectiveness study was done. The device is a diagnostic test that provides a genotype call, not an imaging device or aid to human interpretation that would typically involve human readers.

5. Standalone (i.e., algorithm only without human-in-the-loop performance) study:

   • Yes, the performance studies (Limit of Detection, Method Comparison, Inter-Laboratory Reproducibility, Reagent Lot-to-Lot Reproducibility, Exogenous and Endogenous Interfering Substances) represent standalone performance of the Spartan RX CYP2C19 System. The system integrates and automates the DNA testing process, and results are presented as genotype calls directly, indicating an algorithm-only performance assessment against sequencing-derived ground truth.

6. Type of ground truth used:

   • Bi-directional sequencing was used as the ground truth for all performance studies. This is a highly accurate and widely accepted method for confirming DNA sequences and, thus, genotypes.

7. Sample size for the training set:

   • The document does not explicitly mention a separate training set or its sample size. The reported studies primarily describe validation/test set performance. For molecular diagnostic devices, the development often involves internal optimization and algorithm tuning using various samples, but these are not typically referred to as a "training set" in the same way as machine learning models.

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

   • Since a distinct "training set" is not explicitly defined or discussed in the document for performance evaluation, the method for establishing its ground truth is also not detailed. However, it can be inferred that any samples used during the development and optimization phases would also likely have been characterized using highly accurate methods like bi-directional sequencing, similar to the test sets.

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The xTAG® CYP2D6 Kit v3 is a device used to simultaneously detect and identify a panel of nucleotide variants found within the highly polymorphic CYP2D6 gene located on chromosome 22 from genomic DNA extracted from an EDTA or citrate anticoagulated whole blood sample. This kit can also identify gene rearrangements associated with the deletion (*5) and duplication genotypes. The xTAG® CYP2D6 Kit v3 is a qualitative genotyping assay which can be used as an aid to clinicians in determining therapeutic strategy for therapeutics that are metabolized by the CYP2D6 gene product. This kit is not indicated for stand- alone diagnostic purposes. This test is not intended to be used to predict drug response or non-response.

Not Found

This document is a 510(k) clearance letter for a medical device called the xTAG® CYP2D6 Kit v3. It indicates the device is substantially equivalent to legally marketed predicate devices. However, it does NOT contain the detailed information required to answer your specific questions about acceptance criteria and the study that proves the device meets them.

The letter primarily covers the regulatory approval of the device and its intended use. It does not include:

• A table of acceptance criteria and reported device performance: This sort of data would typically be found in the 510(k) summary or the pivotal study report, not in the clearance letter itself.
• Sample sizes used for the test set and data provenance: Again, this detailed study information is not part of the clearance letter.
• Number of experts and their qualifications for ground truth: This pertains to the study design, not the FDA's regulatory decision letter.
• Adjudication method for the test set: Study design detail absent from this document.
• MRMC comparative effectiveness study details (effect size): This device is a genotyping kit, not an AI-assisted diagnostic imaging device for human readers, so an MRMC study with human readers would not be relevant or performed.
• Standalone algorithm performance: This is a lab kit, not an "algorithm" in the sense of AI software. Its performance is evaluated biochemically/molecularly.
• Type of ground truth used: While the ground truth for genetic testing is typically highly reliable reference methods (e.g., Sanger sequencing, alternative validated genotyping assays), the clearance letter doesn't specify this for this particular study.
• Sample size for the training set: Not applicable as this is not an AI/ML device that requires a training set in that context.
• How ground truth for the training set was established: Not applicable.

In summary, the provided document does not contain the information requested in your prompt regarding acceptance criteria and study details. To find this information, you would typically need to consult the 510(k) summary submitted by the manufacturer to the FDA, which often contains a more detailed description of the performance studies.

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The Verigene® CYP2C19 Nucleic Acid Test (CYP2C19 Test), performed using the sample-to-result Verigene System, is a qualitative multiplexed in vitro diagnostic test for the simultaneous detection and identification of an individual's CYP450 2C19 genotype in genomic deoxyribonucleic acid (DNA) obtained from EDTA-anticoagulated whole blood samples. The Verigene CYP2C19 Nucleic Acid Test (CYP2C19 Test) is indicated for use in clinical laboratories upon prescription by the attending physician as an aid to clinicians in determining therapeutic strategy for therapeutics that are metabolized by the CYP450 2C19 gene product, specifically *2, *3, and *17. The Verigene CYP2C19 Nucleic Acid Test (CYP2C19 Test) is not indicated to be used to predict drug response or non-response.

The Verigene® System is comprised of test consumables and shared instrumentation. All Verigene tests are formatted in self-contained test-specific Verigene Test Cartridges which serve to analyze a nucleic acid sample that is presented to them. Nucleic acids are prepared directly from a whole blood specimen using magnetic glass particles and input automatically into a Test Cartridge inside the Verigene Processor SP. Test progress is tracked and directed by the Verigene Reader instrument, which serves as a central control unit for each Verigene System. Genomic DNA is extracted from the white blood cells in a whole blood specimen, fragmented and denatured. This fragmented, single-stranded genomic DNA hybridizes to complementary sequence-specific DNA oligonucleotides, known as capture oligonucleotides, arrayed on the surface of a substrate (glass slide). A second DNA oligonucleotide is then hybridized to the captured genomic DNA that was captured initially. This oligonucleotide is known as a mediator oligonucleotide containing two sequence domain is complementary to the genomic DNA target and a second domain is complementary to a common oligonucleotide attached to a signal generating gold nanoparticle probe. After washing away any DNA not affixed to the captures, the probe is exposed to the captured mediator/target compound where it hybridizes to any captured mediators. Presence of the gold nanoparticle probes at a particular location on the substrate is assessed optically. The Verigene CYP2C19 Nucleic Acid Test is designed to detect and genotype the CYP450 2C19 *2, *3 and *17 alleles. The test report lists the alleles and provides which genotype was detected in the specimen. The CYP2C19 Test algorithm automatically calculates each of the allele results using a preset normalized ratio of the signal of wild type capture locations on the microarray to the mutant capture locations on the microarray.

This submission focuses on the analytical and clinical performance of the Verigene® CYP2C19 Nucleic Acid Test. Here's a breakdown based on your request:

1. Table of Acceptance Criteria and Reported Device Performance

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

The document describes several test sets used for different studies:

• Analytical Sensitivity / LOD: 7 individual whole blood samples, each with a different genotype. Tested in replicates of 40 (total 280 tests). The data provenance is not specified, but it refers to "individual whole blood samples," suggesting clinical samples. The study appears to be prospective in nature, designed specifically for this validation.
• Interference Testing: 5 individual whole blood samples, each with a different genotype. Tested in 30 replicates per specimen for each interfering substance (total 150 tests per substance, with 5 substances and a control, leading to 900 measurements in Table 2). Data provenance is not specified, but it refers to "EDTA-anticoagulated whole blood samples," suggesting clinical samples. This study appears to be prospective.
• Specimen Stability Study: 35 EDTA whole blood samples. Tested once at 5, 10, 12, and 15 day time points (total 140 tests). Data provenance is not specified (e.g., "freshly-collected whole blood samples"). This study appears to be prospective.
• Carry-over / Cross-contamination: Whole blood specimens containing different genotypes. Tested sequentially on ten Verigene instruments, repeated in triplicate (total number of samples not explicitly stated, but includes "*1/*2, followed by *1/*1, then *1/*17, then *1/*1" repeated in triplicate). Data provenance is not specified. This study appears to be prospective.
• Precision Study: 8 unique whole blood specimens. Each tested in duplicate twice daily by two operators over 12 non-consecutive days at one site (48 replicates per specimen, total 384 data points). Data provenance is not specified. This study appears to be prospective.
• Reproducibility Study: The same 8-member panel of specimens as the Precision Study. Tested in duplicate twice daily by two operators over 5 non-consecutive days at three sites (60 replicates per specimen, total 480 data points). Data provenance is not specified. This study appears to be prospective.
• Method Comparison Study: 670 unique human whole blood samples, collected in EDTA. Data provenance is not specified, but the samples are "human whole blood samples," implying clinical origin. The study appears to be prospective, specifically for method comparison.

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

The ground truth for all performance studies (Analytical Sensitivity, Interference, Precision, Reproducibility, Method Comparison) was established by bi-directional sequencing (BDS). This is a laboratory method, not reliant on human experts for interpretation in the same way imaging studies might be. Therefore, the concept of "number of experts" and their "qualifications" for ground truth establishment is not applicable here.

4. Adjudication Method for the Test Set

Not applicable for this type of laboratory test. The ground truth (bi-directional sequencing) is considered definitive. When the device produced "No Calls" initially, these samples were re-tested, and if successful, contributed to the "Final Call Rate." In the Reproducibility study, the two final "No Call" results were considered discordant. For the Method Comparison study, one sample with an initial and final no-call on the Verigene test had a BDS result of *1/*2, indicating this was a definite discrepancy.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done

No, an MRMC comparative effectiveness study was not conducted. This device is a molecular diagnostic test that provides a genotype result, not an imaging device requiring human reader interpretation.

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

Yes, the performance studies detailed (Analytical Sensitivity, Interference, Stability, Carry-over, Precision, Reproducibility, Method Comparison) represent the standalone performance of the Verigene® CYP2C19 Nucleic Acid Test. The system is described as "sample-to-result" with "automated DNA extraction" and the "Test algorithm automatically calculates each of the allele results." This indicates minimal human intervention in the final result generation once the sample is loaded.

7. The Type of Ground Truth Used

The primary ground truth used for all performance evaluations was bi-directional sequencing (BDS). This is a highly accurate molecular method for determining specific DNA sequences, considered the gold standard for genotyping.

8. The Sample Size for the Training Set

The document does not specify a separate training set or its sample size. This is common for diagnostic tests like this, especially when the underlying technology (genotyping microarray and algorithm) is based on established scientific principles rather than a machine learning model that requires explicit training data in the context of regulatory submissions. The algorithm's parameters are likely "preset" based on scientific design and internal development/optimization rather than a distinct, large-scale training dataset as seen with AI/ML systems.

9. How the Ground Truth for the Training Set was Established

Since no explicit "training set" is described in the context of this 510(k) summary, the method for establishing its ground truth is also not provided. The device's "preset normalized ratio of the signal of wild type capture locations on the microarray to the mutant capture locations on the microarray" implies that the underlying genetic science and expected signal profiles for specific alleles dictate the algorithm's basis, rather than being "trained" on a dataset in the AI/ML sense.

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The eSensor® Warfarin Sensitivity Saliva Test is an in vitro diagnostic test for the detection and genotyping of the *2 and *3 alleles of the cytochrome P450 (CYP450) 2C9 gene locus and the Vitamin K epoxide reductase C1 (VKORC1) gene promoter polymorphism (-1639G>A) from genomic DNA of human saliva samples collected using the Oragene® Dx Device, as an aid in the identification of patients at risk for increased warfarin sensitivity.

The eSensor® Warfarin Sensitivity Saliva Test is a multiplex microarray-based genotyping test system. It is based on the principles of competitive DNA hybridization using a sandwich assay format, wherein a single-stranded target binds concurrently to sequence-specific solution-phase signal probe and solid-phase electrode-bound capture probe. The test employs polymerase chain reaction amplification, exonuclease digestion and hybridization of target DNA. In the process, the double stranded PCR amplicons are digested with exonuclease to generate single stranded DNA suitable for hybridization. Hybridization occurs in the eSensor XT-8 Cartridge (described below) where the singlestranded target DNA is mixed with a hybridization solution containing labeled signal probes.

During hybridization, the target DNA binds to a complementary, single-stranded capture probe immobilized on the working electrode surface. Single-stranded signal probes (labeled with electrochemically active ferrocenes) bind to the target adjacent to the capture probe. When inserted into the eSensor XT-8 instrument (described below), simultaneous hybridization of target to signal probes and capture probe is detected by alternating current voltammetry (ACV). Each pair of working electrodes on the array contains a different capture probe, and sequential analysis of each electrode allows genotyping of multiple mutations or polymorphisms.

The Assay Cartridge (eSensor XT-8 Cartridge): The eSensor XT-8 cartridge device consists of a printed circuit board (PCB) with a multi-layer laminate and a plastic cover that forms a hybridization chamber has a volume of approximately 140 µl. The cartridge consists of a diaphragm pump and check valves (microfluidic components) that circulate the hybridization solution in the hybridization chamber when inserted into the eSensor XT-8 instrument. The PCB chip consists of an array of 72 gold-plated working electrodes, a silver/silver chloride reference electrode, and two gold-plated auxiliary electrodes. Each working electrode has a connector contact pad on the opposite side of the chip for electrical connection to the eSensor XT-8 instrument. Each electrode is modified with a multicomponent, self-assembled monolayer that includes presvnthesized oligonucleotide capture probes specific for each polymorphic site on the test panel and insulator molecules. The cartridge also contains an electrically erasable programmable read-only memory component (EEPROM) that stores information related to the cartridge (e.g., assay identifier, cartridge lot number, and expiration date).

The eSensor XT-8 Instrument (Same as cleared under K073720): The eSensor XT-8 is a clinical multiplex instrument that has a modular design consisting of a base module and one, two, or three cartridge-processing towers containing 8, 16, or 24 cartridge slots, respectively. The cartridge slots operate independently of each other. Any number of cartridges can be loaded at one time, and the remaining slots are available for use while the instrument is running. The base module controls each processing tower, provides power, and stores and analyzes data. The base module includes the user interface, and a 15-in. portrait-orientation display and touch panel. The instrument is designed to be operated solely with the touch screen interface. Entering patient accession numbers and reagent lot codes can be performed by the bar code scanner, the touch screen, or uploading a text file from a USB memory stick. Each processing tower consists of eight cartridge modules, each containing a cartridge connector, a precision-controlled heater, an air pump, and electronics. The air pumps drive the diaphragm pump and valve system in the cartridge, eliminating fluid contact between the instrument and the cartridge. The pneumatic pumping enables recirculation of the hybridization solution allowing the target DNA and the signal probes to hybridize with the complementary capture probes on the electrodes. The diaphragm pump in the cartridge is connected to a pneumatic source from the eSensor XT-8 instrument and provides unidirectional pumping of the hybridization mixture through the microfluidic channel during hybridization. Using microfluidic technology to circulate the hybridization solution minimizes the unstirred boundary layer at the electrode surface and continuously replenishes the volume above the electrode that has been depleted of complementary targets and signal probes. The XT-8 instrument provides electrochemical detection of bound signal probes by ACV and subsequent data analysis and test report generating functions. All hybridization, ACV scanning and analysis parameters are defined by a scanning protocol loaded into the XT-8 Software, and then specified for use by the EEPROM on each cartridge.

The Assay Kit: The Warfarin Sensitivity Saliva Test consists of the test cartridge and the following components: 1) PCR REAGENTS consisting of: PCR Mix [PCR buffer containing primers and dNTP mixture (dCTP, dGTP, dATP, and dUTP)], MgCl2 thermostable DNA polymerase (Taq Polymerase ); and 2 GENOTYPING REAGENTS consisting of: lambda exonuclease, signal probes and hybridization buffer ingredients (Buffer-1 and Buffer-2).

Here's a breakdown of the acceptance criteria and the study details for the eSensor® Warfarin Sensitivity Saliva Test, based on the provided document:

Acceptance Criteria and Device Performance

The acceptance criteria are implied by the comparison to DNA sequencing, which is considered the gold standard for genotyping. The device performance is reported as agreement percentages with DNA sequencing.

Note: The document implies acceptance criteria by comparing the device's performance to DNA sequencing, which is implicitly considered the standard for accuracy. Specific numeric thresholds for "acceptance" are not explicitly stated, but the high agreement percentages (mostly 100%) and the lower bounds of the 95% confidence intervals (LCB) suggest a requirement for high concordance.

Study Information

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

• Sample Size: A total of 316 gDNA samples were extracted from saliva specimens for the method comparison study.
• Data Provenance: The document does not explicitly state the country of origin or if the data was retrospective or prospective. It uses "saliva specimen" without further context on donor recruitment or source.

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

• Experts: Not applicable. The "ground truth" for the genotyping results was established by DNA sequencing, not by human experts.
• Qualifications: Not applicable.

4. Adjudication Method for the Test Set:

• Adjudication Method: Not applicable in the traditional sense of human consensus. The reference method (ground truth) was DNA sequencing. The study reports "No-Calls" and "Miscalls" by the eSensor® device when compared to DNA sequencing. The "After Retest" results suggest that initial "No-Calls" were re-evaluated and resolved, leading to higher agreement.

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:

• MRMC Study: No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is an in-vitro diagnostic (IVD) for genotyping, which is an automated process, not an imaging device requiring human interpretation alongside AI.

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

• Standalone Performance: Yes, the performance reported is essentially a standalone (algorithm only) performance. The eSensor® Warfarin Sensitivity Saliva Test is an automated system that generates results which are then compared to DNA sequencing, without human-in-the-loop interpretation being part of the primary performance evaluation.

7. The Type of Ground Truth Used:

• Ground Truth Type: DNA sequencing (referred to as "bidirectional DNA sequencing" or "DNA Sequencing Result"). This is considered a gold standard for genetic polymorphism detection.

8. The Sample Size for the Training Set:

• Training Set Sample Size: The document does not specify a separate training set. For IVD devices, especially those based on established molecular biology principles, the "training" (development) often involves optimizing reagents and protocols, rather than machine learning algorithm training with distinct datasets. The method comparison study appears to be the primary validation of the device's performance against a reference method.

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

• Training Set Ground Truth: As no explicit training set is mentioned in the context of machine learning, this question is not directly applicable. For the performance validation, as stated above, DNA sequencing was used as the ground truth.

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The INFINITI CYP2C19 Assay is an in vitro diagnostic test for the identification of a patient's CYP450 2C19 genotype in genomic deoxyribonucleic acid (DNA) obtained from EDTA-anticoagulated whole blood samples. The INFINITI CYP2C19 Assay is a qualitative assay for use in clinical laboratories upon prescription by the attending physician.

The INFINITI CYP2C19 Assay is indicated for use as an aid to clinicians in determining therapeutic strategy for therapeutics that are metabolized by the CYP450 2C19 gene product, specifically *2, *3, *17.

The INFINITI CYP2C19 Assay is not indicated to be used to predict drug response or non-response.

The INFINITI CYP2C19 Assay is an in vitro diagnostic device which utilizes proprietary film-based microarray technology combined with process automation, reagent management, and software technology for the detection and genotyping of the 2C19 *2, *3, and *17 mutations in genomic deoxyribonucleic acid (DNA) obtained from EDTA-anticoagulated whole blood samples.

The INFINITI CYP2C19 Assay is comprised of the BioFilmChipTM Microarray, the Intellipac Reagent Module and the PCR Amplification Mix. The INFINITI CYP2C19 Assay should be run using the AutoGenomics INFINITI Analyzer.

The BioFilmChip Microarray consists of a polyester film coated with proprietary multi-layer components designed for DNA analysis. The layers have been designed to provide a versatile surface to enhance test performance. There can be up to 240 spots per microarray with each spot representing a different allele. The microarrays are designed to be assay specific.

The Intellipac Reagent Module contains up four reservoirs that house the test reagents and has an integrated memory chip. Information on the reagent such as lot number, expiration date and remaining tests, are archived in the memory.

The PCR Amplification Mix consists of the reagents needed for the PCR amplification step of the assay.

The INFINITI CYP2C19 Assay is based on the following processes: (a) DNA extraction (b) PCR amplification of purified DNA from human genomic DNA (c) Labeling of the amplified product (allele specific primer extension) (d) Hybridization of the labeled amplified product to a microarray by signature Tag/Capture probe hybridization under isothermal conditions. (e) Scanning of the microarray (f) Signal detection and analysis Steps (c) through (f) are automated by the INFINITI Analyzer. The INFINITI Analyzer automates the 2C19 assay and integrates all the discrete processes of sample (PCR amplicon) handling, reagent management, hybridization, and results The assays are processed automatically and read by the built-in confocal analysis. microscope. Results are analyzed and presented as genotype calls.

Here's an analysis of the acceptance criteria and the study proving the device meets them, based on the provided text:

Acceptance Criteria and Device Performance for INFINITI CYP2C19 Assay

The document focuses on the analytical performance of the device rather than clinical efficacy for patient outcomes or human reader improvement, as it is an in vitro diagnostic device for genotyping. Therefore, some of the requested information, such as effect size of human readers with AI assistance, is not applicable.

1. Table of Acceptance Criteria and Reported Device Performance

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

• Limit of Detection (LOD) Test Set:

  • Sample Size: A total of 1,560 individual tests were completed across various DNA input levels and sample genotypes.
  • Data Provenance: The document implies these were internally generated samples used for development and characterization of the assay. The genotypes (*1/*1, *1/*17, *2/*2, *2/*17) were determined by bi-directional sequencing. The text refers to "whole blood samples," suggesting human samples, but the country of origin is not specified. It is likely retrospective as these are characterized samples used for method validation.

• Percent Agreement vs. Bi-directional Sequencing (Test Set):

  • Sample Size: 317 patient samples.
  • Data Provenance: The samples were "patient samples" tested at "Three sites." They were "de-identified to protect patient's identity." Country of origin is not specified but generally implies samples obtained where the sites are located, likely within the US given the FDA submission. The nature of these being "patient samples" suggests they are clinical samples, used retrospectively for assay validation.

• Assay Inter-Laboratory Reproducibility (Test Sets):

  • Study 1 Sample Size: 12 whole blood samples, resulting in 430 tests.
  • Study 2 Sample Size: 6 genomic whole blood samples, resulting in 255 tests.
  • Combined Sample Size: Across all reproducibility studies, 18 samples were tested, totaling 685 individual replicates/tests.
  • Data Provenance: The samples were "identical samples comprised of whole blood samples." The sites were blinded to sample identity. Like the previous studies, these imply human samples, but the country of origin is not specified. These are clinical samples likely used retrospectively for method validation.

• Interference Test Set:

  • Sample Size: 8 whole blood samples.
  • Data Provenance: Not explicitly stated, but consistent with other studies, likely human whole blood samples used retrospectively for assay validation.

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

For the genetic assays described, the "ground truth" is established through bi-directional sequencing.

• Number of Experts: The document does not specify the number of individuals involved in performing or interpreting the bi-directional sequencing, nor their explicit qualifications (e.g., molecular geneticists, laboratory technologists). However, bi-directional sequencing is a standard molecular biology technique and its interpretation falls under the expertise of qualified laboratory professionals familiar with genetic sequence analysis.
• Qualifications: "Bi-directional sequencing" itself is the gold standard for defining genetic sequences. Thus, the qualification is implied through the choice of this highly accurate method for ground truth determination.

4. Adjudication Method for the Test Set

• Adjudication Method: The document does not describe an explicit "adjudication method" in the typical sense of multiple expert reviewers resolving discrepancies. Instead, the ground truth was established by bi-directional sequencing. For the "no calls" that occurred with the INFINITI assay, the samples were repeated, and the "repeat test gave the correct call." This indicates an internal re-testing protocol for initial "no calls" rather than a formal expert adjudication of differing results between the device and the ground truth. When an "incorrect call" (1 instance) occurred, the root cause was "not definitively determined," suggesting internal review rather than a formal, pre-defined expert adjudication panel.

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

• This question is not applicable to the INFINITI CYP2C19 Assay. This is an in vitro diagnostic (IVD) device directly measuring genetic material, not an imaging or diagnostic support system where a human "reader" (e.g., radiologist) would interact with AI. The device provides genotype calls directly, without human interpretation in the analytical performance step.

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

• Yes, the performance studies described are essentially standalone (algorithm only). The INFINITI Analyzer automates the entire process from hybridization to signal detection and analysis, presenting "genotype calls." The "Percent Agreement vs. Bi-directional Sequencing" and "Inter-Laboratory Reproducibility" studies specifically evaluate the accuracy and consistency of these automated genotype calls against the gold standard (bi-directional sequencing) and across different operational conditions, respectively. Human involvement is in sample preparation, loading, and interpreting the final report, but the "genotype call" generation is automated.

7. The Type of Ground Truth Used

• The primary ground truth used for all performance validation studies (Limit of Detection, Percent Agreement, Reproducibility) was bi-directional sequencing.

8. The Sample Size for the Training Set

• The document does not specify a separate "training set" size for the device's development. This is typical for in vitro diagnostic devices that rely on molecular biology principles and analytical performance rather than machine learning algorithms trained on large datasets. The device's design is based on known genetic sequences and established assay chemistry (PCR, hybridization). The "studies related to specificity were conducted during assay development" (Analytical Specificity section) implies iterative testing and optimization, but not necessarily a distinct, quantified "training set" like in AI/ML applications.

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

• As a formal "training set" is not explicitly mentioned or quantified, this question is largely not applicable in the context of this traditional IVD device.
• For the initial development and optimization of the assay (analogous to internal "training" or development data), the ground truth for samples used would have been established by bi-directional sequencing or other established genotyping methods, as indicated for the LOD studies and as the comparator method for all validation. The "known genomic samples" used for ASP primer specificity determination would also have had their ground truth established by such highly accurate molecular methods.

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