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The ARK Levetiracetam II Assay is a homogeneous enzyme immunoassay intended for the quantitative determination of levetiracetam in human serum or plasma on automated clinical chemistry analyzers. Levetiracetam concentrations can be used as an aid in management of patients treated with levetiracetam.

The ARK Levetiracetam II Assay is a homogeneous immunoassay based on competition between drug in the specimen and levetiracetam labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for binding to the antibody reagent. As the latter binds antibody, enzyme activity decreases. In the presence of drug from the specimen, enzyme activity increases and is directly related to the drug concentration. Active enzyme converts the coenzyme nicotinamide adenine dinucleotide (NAD) to NADH that is measured spectrophotometrically as a rate of change in absorbance. Endogenous serum G6PDH does not interfere with the results because the coenzyme NAD functions only with the bacterial enzyme used in the assay.

The ARK Levetiracetam II Assay consists of reagents R1 anti-levetiracetam monoclonal antibody with substrate and R2 levetiracetam labeled with bacterial G6PDH enzyme.

The provided text describes the performance of a diagnostic assay (ARK Levetiracetam II Assay), not an AI/ML-enabled medical device. Therefore, many of the requested criteria related to AI/ML evaluation (such as MRMC studies, training set details, expert ground truth establishment for AI) are not applicable.

However, I can extract the relevant acceptance criteria and performance data for this in-vitro diagnostic device:

Device Name: ARK Levetiracetam II Assay
Regulatory Class: Class II
Product Code: ORI
Intended Use: Quantitative determination of levetiracetam in human serum or plasma on automated clinical chemistry analyzers, as an aid in management of patients treated with levetiracetam.

Here's the information based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

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

• LoQ: 40 replicates (8 replicates x 5 runs) for each of 3 concentrations (pooled human serum supplemented with levetiracetam).
• Recovery: 6 replicates (3 replicates x 2 analytical runs) for each concentration (human serum negative for levetiracetam, spiked with drug).
• Linearity: 6 replicates (3 replicates x 2 analytical runs) for each dilution (human serum, spiked with drug and diluted).
• Method Comparison: 104 samples (levetiracetam concentrations 3.4 ug/mL to 98.3 ug/mL). No specific provenance (e.g., country of origin) is mentioned, but the samples are clinical human samples or quality control materials. The study is a prospective analytical study comparing two assays.
• Precision: 160 replicates per sample/control level (quadruplicate twice a day for 20 non-consecutive days) for tri-level controls and three human serum samples.
• Interfering Substances: 6 replicates (3 replicates x 2 analytical runs) for each interfering substance level in two known levetiracetam concentrations (human serum).
• Metabolites/Drug Interference: Not explicitly stated, but similar to interfering substances: "high concentration of each compound was spiked into normal human serum with known levels of levetiracetam."

The data provenance is from analytical studies conducted by the manufacturer, likely in a laboratory setting, using human serum/plasma samples/materials. The document does not specify country of origin for the samples/data, beyond "human serum/plasma". These are prospective analytical studies designed to characterize the device's performance.

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

This section is not applicable as the document describes an in-vitro diagnostic assay for quantitative determination of a drug. The "ground truth" for such an assay is established by the known concentrations of calibrators, controls, and spiked samples, and comparison to a legally marketed predicate device using analytical methods (e.g., spectrophotometry). There are no human "experts" establishing a "ground truth" in the sense of image interpretation or clinical diagnosis.

4. Adjudication Method for the Test Set

Not applicable. This is an in-vitro diagnostic device providing quantitative measurements. There is no qualitative assessment or interpretation by multiple readers that would require an adjudication method.

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

No. This is an in-vitro diagnostic assay, not an AI/ML medical device where human readers interact with AI.

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

Yes, in essence. The performance studies (LoQ, Recovery, Linearity, Precision, Interference) demonstrate the "standalone" performance of the assay itself, as an automated clinical chemistry analyzer performs the measurements. There is no human-in-the-loop variable in the measurement process of an immunoassay. The output is a quantitative value, not a diagnostic interpretation that a human would then use as "assistance."

7. The Type of Ground Truth Used

The ground truth used for performance evaluation is primarily:

• Known concentrations: For LoQ, Recovery, Linearity, Interfering Substances, Metabolites, and Drug Interference studies, concentrations of levetiracetam and potential interferents are precisely measured, prepared, or spiked into matrices.
• Reference Method/Predicate Device: For Method Comparison, the predicate ARK Levetiracetam Assay performed on the Roche/Hitachi 917 serves as the comparative "reference" for evaluating the substantial equivalence of the new assay. This is a common practice for IVD assays.

8. The Sample Size for the Training Set

Not applicable. This is a reagent-based immunoassay, not an AI/ML algorithm that requires a training set in the typical sense for machine learning. The "development" or "training" of such a diagnostic involves chemical formulation, antibody development, and optimization of reaction conditions, not data-driven model training.

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

Not applicable. As explained above, there is no AI/ML training set in this context.

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The ARK Methotrexate II Assay is a homogeneous enzyme immunoassay intended for the quantitative determination of methotrexate in human serum or plasma on automated clinical chemistry analyzers. The measurements obtained are used in monitoring levels of methotrexate to help ensure appropriate therapy. Specimens from patients who have received glucarpidase (carboxypeptidase G2) as a high dose methotrexate rescue therapy should not be tested with the ARK Methotrexate II Assay.

The ARK Methotrexate II Assay is a homogeneous immunoassay based on competition between drug in the specimen and methotrexate labeled with the recombinant enzyme glucose-6phosphate dehydrogenase (rG6PDH) for binding to the antibody reagent. As the latter binds antibody, enzyme activity decreases. In the presence of drug from the specimen, enzyme activity increases and is directly related to the drug concentration. Active enzyme converts the coenzyme nicotinamide adenine dinucleotide (NAD) to NADH that is measured spectrophotometrically as a rate of change in absorbance. Endogenous serum G6PDH does not interfere with the results because the coenyzme NAD functions only with the bacterial enzyme (rG6PDH) used in the assay. The ARK Methotrexate II Assay consists of reagents R1 anti-methotrexate monoclonal antibody with substrate and R2 methotrexate labeled with recombinant G6PDH enzyme. The test system includes the ARK Methotrexate II Calibrator, ARK Methotrexate II Control, and ARK Methotrexate II Dilution Buffer.

The ARK Methotrexate II Assay is a homogeneous enzyme immunoassay for the quantitative determination of methotrexate in human serum or plasma.

Here's an analysis of the acceptance criteria and the study proving the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance:

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

• Clinical Accuracy (vs. LC-MS/MS): 90 patient samples.
• Method Comparison (vs. Predicate Device): 123 patient samples.
• LoQ, Recovery, Linearity, Precision, Interference, Analytical Specificity: These studies involved spiked human serum samples, pooled human serum, and controls, rather than a specific number of unique patient samples for the test set. For LoQ, 40 replicates were tested. For Recovery, 6 replicates per sample were tested. For Linearity, 6 replicates per sample were tested. For Precision, 160 replicates were tested for each of the 6 control levels and 6 human serum levels. For Interference and Analytical Specificity, 6 replicates per sample were tested.
• Data Provenance: "Leftover specimens were obtained from persons receiving high-dose methotrexate therapy" for the method comparison studies. The document does not specify the country of origin of the data or whether the studies were retrospective or prospective, though "leftover specimens" suggests a retrospective collection.

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

• The ground truth for the clinical accuracy study was established by an LC-MS/MS reference method. This is an analytical laboratory technique, not based on expert consensus. Therefore, no "experts" in the traditional sense (e.g., radiologists) were used for ground truth establishment. The performance of LC-MS/MS as a reference method typically implies its results are considered the gold standard.

4. Adjudication Method for the Test Set:

• Not applicable. The ground truth for the clinical accuracy and method comparison studies was established using objective analytical methods (LC-MS/MS and the predicate device), not through expert review requiring an adjudication method.

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:

• Not applicable. This device is an in vitro diagnostic (IVD) assay for quantitative determination of a substance in human samples. It does not involve human readers interpreting medical images or data.

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

• Yes, the performance data presented (Limit of Quantitation, Measurement Range, Recovery, Linearity, Clinical Accuracy, Method Comparison, Precision, Interference, Analytical Specificity) reflects the standalone performance of the ARK Methotrexate II Assay (an automated immunoassay) without human intervention in the result generation. The device itself is designed to provide quantitative measurements.

7. The Type of Ground Truth Used:

• Clinical Accuracy: Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS) was used as the reference method (gold standard) for ground truth.
• Method Comparison: The legally marketed predicate device, ARK™ Methotrexate Assay (K111904), was used to compare results.
• Other performance metrics (LoQ, Recovery, Linearity, Precision, Interference, Analytical Specificity): Ground truth was established by preparing samples with known concentrations of methotrexate or interfering substances, typically by spiking human serum with certified reference materials.

8. The Sample Size for the Training Set:

• Not applicable. This device is an immunoassay (laboratory test kit), not a machine learning or AI algorithm that requires a "training set" in the conventional sense of computational models. The development and optimization of the assay would involve various experiments and reagent formulations, but not a distinct "training set" like for AI models.

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

• Not applicable, as there is no "training set" in the context of an AI/ML algorithm for this type of medical device. The "ground truth" for the development of the assay components would involve standard analytical chemistry practices, such as using reference materials and established analytical methods to verify the concentration and purity of substances used in the reagents.

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The ARK Hydrocodone Assay is an immunoassay intended for the qualitative detection and/or semi-quantitative estimation of hydrocodone and its metabolites in human urine at a cutoff of 300 ng/mL. The semi-quantitative mode is for the purpose of (1) enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method, such as Gas Chromatography/Mass Spectrometry (GC/MS) or Liquid Chromatography/tandem Mass Spectrometry (LC-MS/MS), or (2) permitting laboratories to establish quality control procedures.

The ARK Hydrocodone Assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used in order to obtain a confirmed positive analytical result. Gas Chromatography/Mass Spectrometry (GC/MS) or Liquid Chromatography/tandem Mass Spectrometry (LC-MS/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug test result, particularly when the preliminary test result is positive.

The ARK Hydrocodone Assay is supplied as a liquid ready-to-use homogeneous enzyme immunoassay. The assay is based on competition between hydrocodone in the specimen and hydrocodone labeled with recombinant glucose-o-phosphate dehydrogenase (rG6PDH) for antibody binding sites. As the latter binds antibody, enzyme activity decreases. In the presence of hydrocodone from the specimen, enzyme activity increases and is directly related to the hydrocodone concentration. Active enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH in the presence of glucose-6-phosphate (G6P), resulting in an absorbance change that is measured spectrophotometrically. Endogenous G6PDH does not interfere because the coenzyme NAD functions only with the bacterial enzyme used in the assay.

The ARK Hydrocodone Assay consists of reagents R1 anti-hydrocodone monoclonal rabbit antibodies with substrate and R2 hydrocodone derivative labeled with bacterial recombinant G6PDH enzyme.

The provided document is a 510(k) summary for the ARK Hydrocodone Assay, an immunoassay for the qualitative detection and/or semi-quantitative estimation of hydrocodone and its metabolites in human urine.

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

1. Table of Acceptance Criteria & Reported Device Performance:

The document doesn't explicitly define formal "acceptance criteria" in a separate table with numerical thresholds for accuracy, precision, etc. Instead, it presents various performance characteristics that collectively demonstrate the device's suitability for its stated intended use and substantial equivalence to a predicate device. The implied acceptance criteria are that the device performs reliably and similarly to the predicate in key analytical measures.

Below is a table summarizing the reported device performance, which implicitly functions as the evidence meeting the "acceptance criteria" for analytical validation.

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

• Precision Studies: N=160 for both qualitative and semi-quantitative precision (quadruplicate assays twice a day for 20 days for 8 concentration levels).
• Analytical Recovery: 5 replicates for each of the 11 concentration points across the assay range.
• Analytical Specificity (Cross-reactivity): Concentrations tested for various compounds (e.g., 100,000 ng/mL, 50,000 ng/mL). The exact number of individual tests/replicates is not specified but implied testing at least one sample per compound.
• Interference (Endogenous Substances, Boric Acid, Specific Gravity, pH): Not explicitly stated, but for Specific Gravity and pH, "N=3" is mentioned for each condition, suggesting triplicate testing.
• Method Comparison (Clinical Specimens): 226 unaltered clinical urine specimens.
• Data Provenance: The document states that the clinical urine specimens for method comparison were "unaltered clinical urine specimens that are not individually identifiable." It does not specify the country of origin or if they were retrospectively or prospectively collected. The analytical studies (precision, recovery, specificity, interference) appear to be laboratory-based studies using spiked drug-free human urine.

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

This information is not provided in the document. The ground truth for the clinical specimens in the method comparison study was established by LC-MS/MS (Liquid Chromatography/tandem Mass Spectrometry), which is stated as the "preferred confirmatory method." LC-MS/MS is an analytical chemistry technique, not a human expert interpretation.

4. Adjudication Method for the Test Set:

This information is not applicable/provided. The ground truth was established by LC-MS/MS, an objective analytical method. Therefore, there was no need for human expert adjudication.

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is an immunoassay (a laboratory diagnostic test), not an imaging AI or a device that assists human readers in interpreting complex data. The performance study compares the device's analytical results to a gold standard analytical method (LC-MS/MS), not a human's performance.

6. If a Standalone (Algorithm Only Without Human-In-The-Loop Performance) was done:

The device itself is a "standalone" test in the sense that it provides a direct analytical result (qualitative or semi-quantitative) without human interpretation of raw data for diagnosis. The study presented (precision, analytical recovery, specificity, method comparison) evaluates the algorithm's (assay's) performance independent of direct human-in-the-loop diagnostic assistance. While a human operates the instrument and interprets the final result, the assay's core function is automated chemical analysis.

7. The Type of Ground Truth Used:

The primary ground truth used for the method comparison study was LC-MS/MS (Liquid Chromatography/tandem Mass Spectrometry) results. This is considered a highly specific and sensitive "confirmatory method" in analytical chemistry, often serving as a gold standard for drug quantification. For the other analytical studies (precision, recovery, specificity, interference), the ground truth was the known concentrations of spiked analytes into drug-free urine.

8. The Sample Size for the Training Set:

This information is not applicable/provided. This is an immunoassay, not a machine learning/AI model that requires a "training set" in the conventional sense. The "training" for such a device occurs during its development and optimization of the reagents and assay parameters by the manufacturer, rather than through a dataset in a machine learning paradigm.

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

As mentioned above, this concept doesn't directly apply here. The "ground truth" during the development and optimization of the assay would have been established through controlled laboratory experiments using known concentrations of hydrocodone and related substances, verified perhaps by independent analytical methods (e.g., HPLC, LC-MS/MS) and chemical purity assessments. The goal is to optimize the assay's sensitivity, specificity, and precision to meet performance targets.

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The ARK Lacosamide Assay is a homogeneous enzyme immunoassay intended for the quantitative determination of lacosamide in human serum on automated clinical chemistry analyzers. The measurements obtained are used in monitoring levels of lacosamide to help ensure appropriate therapy.

The ARK Lacosamide Assay is a homogeneous enzyme immunoassay based on competition between drug in the specimen and lacosamide labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for binding to the antibody reagent. As the latter binds antibody, enzyme activity decreases. In the presence of drug from the specimen, enzyme activity increases and is directly related to the drug concentration. Active enzyme converts the coenzyme nicotinamide adenine dinucleotide (NAD) to NADH that is measured spectrophotometrically as a rate of change in absorbance. Endogenous serum G6PDH does not interfere with the results because the coenzyme NAD functions only with the bacterial enzyme used in the assay.

The ARK Lacosamide Assay consists of reagents R1 anti-lacosamide polyclonal antibody with substrate and R2 lacosamide labeled with bacterial G6PDH enzyme.

The provided text describes the ARK Lacosamide Assay, a homogeneous enzyme immunoassay for quantitative determination of lacosamide in human serum. This device is intended for monitoring lacosamide levels to ensure appropriate therapy. The substantial equivalence is demonstrated through comparative testing against a predicate device (ARKTM Topiramate Assay, K083799) and various performance characteristic studies.

Here's a breakdown of the acceptance criteria and study details:

1. Table of Acceptance Criteria and Reported Device Performance:

2. Sample size used for the test set and the data provenance:

• LoQ: 40 replicates (8 replicates x 5 runs) for each of 3 concentrations. Data provenance is implied to be laboratory-generated (pooled human serum supplemented with lacosamide).
• Measurement Range: Not a directly tested "test set" in terms of patient samples; rather, it refers to the range characterized by other studies like recovery and linearity.
• Recovery: Not explicitly stated as a separate "test set" size for recovery studies, but involved adding concentrated lacosamide to pooled human serum. "Two analytical runs of three replicates of each sample were assayed."
• Linearity: Dilutions of a 30.00 µg/mL lacosamide serum sample. "Two analytical runs of three replicates of each sample were assayed."
• Method Comparison: 150 unaltered, human serum specimens. The data provenance is described as "human serum specimens" which implies retrospective clinical samples, but the country of origin is not specified. They are "not individually identifiable."
• Precision: 160 replicates for each of 6 samples/controls (quadruplicate twice a day for 20 days). Implied laboratory-generated (tri-level controls and pooled human serum with lacosamide).
• Interfering Substances: For each interfering substance, lacosamide was present at 2 concentrations (2.0 and 15.0 µg/mL). "Two analytical runs of three replicates of each sample (6 replicates total) were assayed." Implied laboratory-generated.
• Specificity (O-Desmethyl Metabolite): Assayed lacosamide at 2 concentrations (2.00 and 15.00 µg/mL) in the absence and presence of the metabolite at 2 concentrations (5.0 and 30.0 µg/mL). Implied laboratory-generated.
• Crossreactivity (Other Drugs): For each of 77 compounds, lacosamide was present at 2 concentrations (2.00 and 15.00 µg/mL). Implied laboratory-generated.
• Sample Stability: Not a statistical "test set" but based on supporting data; implies samples stored under different conditions.

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

• This device is an in vitro diagnostic assay that measures a chemical compound (lacosamide concentration). The "ground truth" for method comparison studies is established by a reference method, not by expert interpretation.
• In the method comparison study, the ARK Lacosamide Assay results were compared against LC-MS/MS (Liquid Chromatography-Mass Spectrometry/Mass Spectrometry). LC-MS/MS is a highly accurate and sensitive analytical chemistry technique, often considered a "gold standard" for quantifying small molecules like drugs in biological matrices.
• Therefore, no human experts were used to establish the ground truth; instead, an established analytical method served as the reference.

4. Adjudication method for the test set:

• Not applicable as the ground truth is established by a quantitative analytical method (LC-MS/MS), not by human interpretation or consensus.

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:

• Not applicable. This device is an in vitro diagnostic assay, not an AI-powered diagnostic imaging or interpretation tool that assists human readers.

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

• Yes, the performance characteristics described (LoQ, Measurement Range, Recovery, Linearity, Precision, Interfering Substances, Specificity, Crossreactivity, Stability) are all standalone algorithm (assay) performance studies. The method comparison study also evaluated the standalone performance of the ARK Lacosamide Assay against LC-MS/MS.
• The device explicitly states it is "intended for the quantitative determination of lacosamide in human serum on automated clinical chemistry analyzers," indicating standalone operation with human oversight rather than human-in-the-loop interpretation of complex data.

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

• For the method comparison study, the ground truth was "results from LC-MS/MS," which is a reference analytical method.
• For other performance studies (LoQ, recovery, linearity, precision, interference, specificity, cross-reactivity), the ground truth was based on the known concentrations of lacosamide and interfering substances added to human serum samples.

8. The sample size for the training set:

• This is an in vitro diagnostic assay, not a machine learning or AI model that requires a "training set" in the conventional sense. The development of the assay's reagents and methodologies involves analytical chemistry and biochemical principles rather than statistical training on data.

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

• Not applicable for the reasons stated in point 8. The "ground truth" for the development of this assay would be the accurate chemical characterization of lacosamide and its antibodies, and the optimization of the enzymatic reaction to accurately reflect lacosamide concentration.

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The ARK Fentanyl II Assay is an immunoassay intended for the qualitative detection of fentanyl in human urine at a cutoff concentration of 1.0 ng/mL. The assay is intended for use in laboratories with automated clinical chemistry analyzers. This in vitro diagnostic device is for prescription use only.

The ARK Fentanyl II Assay provides only a preliminary analytical result. A more specific alternative chemical method must be used in order to obtain a confirmed positive analytical result. Gas Chromatography/Mass Spectrometry (GC/MS) or Liquid Chromatography/tandem Mass Spectrometry (LC-MS/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug test result, particularly when the preliminary test result is positive.

The ARK Fentanyl II Assay is a homogeneous enzyme immunoassay technique used for the analysis of a specific compound in human urine. The assay is based on competition between drug in the specimen and drug labeled with recombinant glucose-6-phosphate dehydrogenase (rG6PDH) for antibody binding sites. As the latter binds antibody, enzyme activity decreases. In the presence of drug from the specimen, enzyme activity increases and is directly related to the drug concentration. Active enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH in the presence of glucose-6-phosphate (G6P), resulting in an absorbance change that is measured spectrophotometrically. Endogenous serum G6PDH does not interfere because the coenzyme NAD functions only with the bacterial enzyme used in the assay.

The ARK Fentanyl II Assay consists of reagents R1 anti-fentanyl monoclonal antibodies with substrate and R2 fentanyl derivative labeled with bacterial recombinant G6PDH enzyme.

1. Acceptance Criteria and Reported Device Performance for ARKTM Fentanyl II Assay

The provided text details the performance characteristics of the ARKTM Fentanyl II Assay, which is an immunoassay for the qualitative detection of fentanyl in human urine at a cutoff concentration of 1.0 ng/mL. The study evaluates precision, analytical specificity (cross-reactivity with structurally similar compounds and lack of interference from structurally unrelated compounds and endogenous substances), and method comparison with LC-MS/MS.

Here's a table summarizing the acceptance criteria (implied by the data presentation for each test) and the reported device performance:

Study Details:

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

   • Precision Study: N=160 for each of 9 concentration levels (total 1440 measurements). The samples were drug-free human urine supplemented with fentanyl. Data provenance is not explicitly stated as country of origin, but described as "drug-free, negative human urine", implying laboratory-prepared samples.
   • Analytical Specificity (Cross-reactivity/Interference): Samples were drug-free, negative human urine spiked with various compounds and fentanyl. Specific sample sizes for each compound tested are not provided, but generally involve multiple replicates for dose-response evaluation or testing with fentanyl-spiked urine.
   • Method Comparison: A total of 147 unaltered clinical urine specimens were used. The data provenance is not explicitly mentioned as country of origin, but it is stated these were "unaltered clinical urine specimens that are not individually identifiable." This suggests a retrospective collection of clinical samples.

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

   • The ground truth for the method comparison study was established by LC-MS/MS (Liquid Chromatography/tandem Mass Spectrometry), which is described as the "preferred confirmatory method" and was performed by a "licensed reference laboratory." This is an objective, analytical method, not reliant on human expert interpretation for the quantitative values. Therefore, individual human "experts" in the traditional sense (e.g., radiologists) were not used to establish the ground truth in this context. The expertise lies in the certified analytical process and the laboratory standards.

3. Adjudication method for the test set:

   • No adjudication method (e.g., 2+1, 3+1) was applicable or mentioned, as the ground truth was established by quantitative analytical methods (LC-MS/MS), not by human expert review requiring consensus.

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:

   • This is an in vitro diagnostic immunoassay and not an AI-powered image analysis or medical device that involves human readers/interpreters in its primary function. Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance was not conducted and is irrelevant to this device type. The device provides a direct analytical result.

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

   • Yes, the performance presented is a standalone performance of the immunoassay system. It measures the algorithm's (immunoassay's) ability to detect fentanyl in urine samples independently of human intervention for result interpretation. The results are generated by an "automated clinical chemistry analyzer."

6. The type of ground truth used:

   • For the method comparison study, the ground truth was quantitative analytical data from LC-MS/MS (Liquid Chromatography/tandem Mass Spectrometry). This is a highly specific and sensitive confirmatory laboratory method.

7. The sample size for the training set:

   • This document describes a premarket notification (510(k)) for an in vitro diagnostic device (immunoassay). For such devices, internal development and optimization (which can be considered analogous to "training") occur during the assay design and reagent formulation phases. However, the FDA 510(k) submission typically focuses on the validation (test set) of the finalized device rather than detailed disclosure of the "training set" in the context of machine learning. The document does not specify a sample size for a training set in the way it would for a machine learning algorithm. The "training" here would involve iterative testing and refinement of antibody characteristics, enzyme conjugates, and reagent formulations using proprietary in-house samples until the desired performance (specificity, sensitivity, dynamic range) is achieved.

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

   • As mentioned above, the concept of a "training set" with established ground truth in the machine learning sense is not directly applicable to this traditional immunoassay. The development process would involve:
     • Synthesizing or acquiring known concentrations of fentanyl and its metabolites.
     • Evaluating various antibody candidates and enzyme conjugates against these known concentrations.
     • Spiking drug-free human urine to create samples with precisely known concentrations of analytes.
     • Using highly accurate analytical methods (like GC/MS or LC-MS/MS) internally to confirm the concentrations of prepared samples or to guide dose-response adjustments during reagent formulation.
   • Ultimately, the ground truth for any "training" or optimization would be based on known chemical concentrations of the target analyte and potential interferents, confirmed by reference analytical methods.

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The ARK Tramadol Assay is an immunoassay intended for the qualitative and/or semiquantitative determination of tramadol in human urine at a cutoff concentration of 100 ng/mL. The assay is intended for use in laboratories with automated clinical chemistry analyzers. This in vitro diagnostic device is for prescription use only.

The semiquantitative mode is for the purpose of (1) enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method, such as Gas Chromatography/Mass Spectrometry (GC/MS) or Liquid Chromatography/tandem Mass Spectrometry (LC-MS/MS), or (2) permitting laboratories to establish quality control procedures.

The ARK Tramadol Assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used in order to obtain a confirmed positive analytical result. Gas Chromatography/Mass Spectrometry (GC/MS) or Liquid Chromatography/tandem Mass Spectrometry (LC-MS/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug test result, particularly when the preliminary test result is positive.

The ARK Tramadol Assay is a homogeneous enzyme immunoassay technique used for the analysis of tramadol in human urine. The assay is based on competition between drug in the specimen and drug labeled with recombinant glucose-6-phosphate dehydrogenase (rG6PDH) for antibody binding sites. As the latter binds antibody, enzyme activity decreases. In the presence of drug from the specimen, enzyme activity increases and is directly related to the drug concentration. Active enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH in the presence of glucose-6-phosphate (G6P), resulting in an absorbance change that is measured spectrophotometrically. Endogenous G6PDH does not interfere because the coenzyme NAD functions only with the bacterial enzyme used in the assay.

The ARK Tramadol Assay consists of reagents R1 anti-tramadol rabbit polyclonal antibody with substrate and R2 tramadol derivative labeled with bacterial recombinant G6PDH enzyme.

The provided text describes the performance characteristics of the ARK Tramadol Assay, an immunoassay for detecting tramadol in human urine. Here's a breakdown of the acceptance criteria and study details:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" in a bulleted or numbered list with corresponding "reported performance." However, the performance parameters evaluated and the results presented implicitly define the acceptance criteria for the device to be considered substantially equivalent to the predicate. Based on the provided data, the implicit acceptance criteria and the device's performance are:

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

• Precision Studies: 160 determinations for each of 9 concentration levels (0.0 to 200.0 ng/mL) for both qualitative and semiquantitative modes. This totals 160 * 9 = 1440 individual measurements across 20 days. The samples were
  • Data Provenance: Drug-free, negative human urine that was spiked with tramadol to create the test concentrations. The geographic origin of the human urine or whether it was retrospective/prospective is not specified beyond "human urine."
• Analytical Recovery: Not explicitly stated, but "N=6" is mentioned for the mean concentration calculation at each of the 11 tested levels. So, 6 samples for each of 11 concentrations (50.0 to 1000.0 ng/mL) were used. These were also dilutions from drug-free, negative human urine spiked with tramadol.
• Analytical Specificity (Metabolites and Structurally Related Compounds): Not explicitly stated, but compounds were "spiked into drug-free, negative human urine." The number of samples per compound is not specified, but each compound was tested.
• Interference (Structurally Unrelated Compounds & Endogenous Substances): Not explicitly stated for each concentration or substance, but involved "High concentrations of the following structurally unrelated compounds/endogenous substances were added into urine spiked with tramadol (± 25% of the cutoff concentration) and tested."
• Interference (Specific Gravity, pH, Boric Acid): Samples were spiked urine (± 25% of cutoff) manipulated for specific gravity/pH or with boric acid added. The number of samples is not explicitly stated per condition.
• Method Comparison: A total of 115 unaltered clinical human urine specimens.
  • Data Provenance: "clinical human urine specimens that are not individually identifiable." No country of origin is specified, but "unaltered clinical human urine specimens" suggests real-world samples. Whether retrospective or prospective is not explicitly stated.

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

• This is an in vitro diagnostic (IVD) device for chemical analysis, not an imaging or clinical interpretation device. Therefore, the concept of "experts" establishing ground truth in the way a radiologist would for an image is not applicable.
• For the method comparison study, the ground truth was established by a "licensed reference laboratory" using Gas Chromatography/Mass Spectrometry (GC/MS) or Liquid Chromatography/tandem Mass Spectrometry (LC-MS/MS), which are considered the gold standard confirmatory methods for drug testing. The qualifications of the personnel performing these confirmatory tests are inherent to the "licensed reference laboratory" performing a gold-standard chemical analysis, rather than subjective expert opinion.

4. Adjudication Method for the Test Set

• Not applicable as this is a chemical assay with objective measurements (spectrophotometric absorbance changes) and comparison to a definitive analytical method (LC-MS/MS) for ground truth. Discrepancies in the method comparison were analytically explained (e.g., cross-reactivity with O-desmethyltramadol) rather than requiring human adjudication of subjective interpretations.

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, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study design is typically used for medical imaging devices or other diagnostic tools where human interpretation plays a significant role. The ARK Tramadol Assay is an automated immunoassay for chemical analysis, not a device requiring human "readers" in the context of an MRMC study.

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

• Yes, this entire study represents a standalone performance evaluation. The ARK Tramadol Assay is an automated immunoassay performed on "automated clinical chemistry analyzers." Its performance is directly compared to an established analytical method (LC-MS/MS), without "human-in-the-loop" interpretation as a primary output of the device itself. The results are quantitative (in semiquantitative mode) or qualitative (positive/negative), derived directly from the instrument's measurements.

7. The Type of Ground Truth Used

• The ground truth used was confirmatory analytical methods, specifically Gas Chromatography/Mass Spectrometry (GC/MS) or Liquid Chromatography/tandem Mass Spectrometry (LC-MS/MS), which are considered the gold standard for drug detection and quantification in biological samples.

8. The Sample Size for the Training Set

• The document does not provide information about a "training set" in the context of machine learning or AI. This device is an immunoassay, whose performance is based on established biochemical principles and reagents, not a machine learning algorithm that is "trained" on data. The studies described are method development and validation studies to establish the assay's analytical performance.

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

• As noted in point 8, there is no "training set" in the context of this immunoassay. The concept of "ground truth for a training set" is therefore not applicable. The assay's design and reagents are based on antibody-antigen binding principles rather than data-driven machine learning.

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The ARK EDDP Assay is an immunoassay intended for the qualitative and/or semiquantitative determination of EDDP in human urine at cutoff concentrations of 100 ng/mL and 300 ng/mL. The assay is intended for use in laboratories with automated clinical chemistry analyzers. This in vitro diagnostic device is for prescription use only.

The semiquantitative mode is for the purpose of (1) enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method, such as Gas Chromatography/Mass Spectrometry (GC/MS) or Liquid Chromatography/tandem Mass Spectrometry (LC-MS/MS), or (2) permitting laboratories to establish quality control procedures.

The ARK EDDP Assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used in order to obtain a confirmed positive analytical result. Gas Chromatography/Mass Spectrometry (GC/MS) or Liquid Chromatography/tandem Mass Spectrometry (LC-MS/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug test result, particularly when the preliminary test result is positive.

The ARK EDDP Assay is a homogeneous enzyme immunoassay technique used for the analysis of EDDP in human urine. The assay is based on competition between EDDP in the specimen and EDDP labeled with recombinant glucose-6-phosphate dehydrogenase (rG6PDH) for antibody binding sites. As the latter binds antibody, enzyme activity decreases. In the presence of EDDP from the specimen, enzyme activity increases and is directly related to the EDDP concentration. Active enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH in the presence of glucose-6-phosphate (G6P), resulting in an absorbance change that is measured spectrophotometrically. Endogenous G6PDH does not interfere because the coenzyme NAD functions only with the bacterial enzyme used in the assay.

The ARK EDDP Assay consists of reagents R1 anti-EDDP rabbit antibody with substrate and R2 EDDP derivative labeled with bacterial recombinant G6PDH enzyme.

Here's a breakdown of the acceptance criteria and study details for the ARK EDDP Assay, based on the provided FDA 510(k) summary:

This document describes a medical device, the ARK EDDP Assay, which is an immunoassay for the qualitative and/or semi-quantitative determination of EDDP (a methadone metabolite) in human urine. The study presented is a non-clinical performance evaluation, as indicated by "Brief Description of Nonclinical and Clinical Data" and the nature of the tests (Precision, Analytical Recovery, Analytical Specificity, Interference, etc.). No clinical study involving human patients or human readers in an MRMC setting is described.

1. A table of acceptance criteria and the reported device performance

The document doesn't explicitly state "acceptance criteria" as a single, consolidated table with specific pass/fail values for each performance characteristic. Instead, performance is evaluated against expected behaviors for an in vitro diagnostic (IVD) device of this type. The inferred acceptance criteria are that the device should demonstrate acceptable precision, accurate analytical recovery, appropriate cross-reactivity and interference profiles, and good agreement with a gold standard (GC/MS) in method comparison for qualitative and semi-quantitative results.

2. Sample sizes used for the test set and the data provenance

• Precision Studies:
  • Target Concentrations: 9 levels for each cutoff (0.0 to 200.0 ng/mL for 100 ng/mL cutoff; 0.0 to 600.0 ng/mL for 300 ng/mL cutoff).
  • Replicates: Quaduplicate twice a day for 20 days.
  • Total Sample Size per Cutoff (for precision): 9 levels * 4 replicates * 2 (times/day) * 20 days = 1440 individual readings for the qualitative precision tables. (Note: The table summary states N=160 for each concentration level, implying 160 results for each of the 9 spiked levels.)
  • Data Provenance: Drug-free, negative human urine (spiked with EDDP). The country of origin is not specified but is likely the U.S. as it's an FDA submission. This is a prospective study (laboratory testing).
• Analytical Recovery:
  • Target Concentrations: 12 levels (50.0 to 1000.0 ng/mL).
  • Replicates: N=6 for mean concentration calculation.
  • Total Sample Size: 12 levels * 6 replicates = 72 individual readings.
  • Data Provenance: Drug-free, negative human urine (spiked with EDDP). Prospective laboratory testing.
• Analytical Specificity (Cross-reactivity):
  • Number of Compounds Tested: 7 structurally related compounds.
  • Sample Size: Each compound tested at minimum concentration for positive result (or highest tested) at both cutoff levels. Implies multiple tests per compound, but specific N is not given per compound; typically, this would be triplicate.
  • Data Provenance: Drug-free, negative human urine (spiked with compounds). Prospective laboratory testing.
• Interference (Structurally Unrelated, Endogenous Substances, Specific Gravity, pH):
  • Number of Compounds/Conditions Tested: Numerous (tens of compounds + SG and pH conditions).
  • Sample Size: Each compound/condition tested at two EDDP levels (±25% of cutoff). Implies multiple tests per condition, but specific N is not given per condition; typically, this would be triplicate.
  • Data Provenance: Drug-free, negative human urine (spiked with EDDP and interferent). Prospective laboratory testing.
• Method Comparison:
  • Sample Size: 109 unaltered clinical human urine specimens.
  • Data Provenance: "unaltered clinical human urine specimens that are not individually identifiable." Country of origin not specified, but usually implies local (US) clinical samples. Described as "clinical human urine specimens," suggesting these were collected from actual patients, making this a retrospective evaluation of real-world samples.

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

The ground truth for this diagnostic device is established by Gas Chromatography/Mass Spectrometry (GC/MS) or Liquid Chromatography/tandem Mass Spectrometry (LC-MS/MS), which are highly accurate analytical chemistry techniques considered the gold standard for drug confirmation in urine. These methods are performed in laboratories by trained laboratory professionals (analytical chemists, toxicologists). The document states the GC/MS confirmatory method was performed by a "licensed reference laboratory."

• Number of experts: Not explicitly stated, as GC/MS analysis is a scientific measurement, not typically an "expert reader" interpretation process like image analysis. The "experts" are the qualified laboratory personnel operating and interpreting the GC/MS results.
• Qualifications of experts: Implied to be qualified laboratory professionals with expertise in analytical chemistry and toxicology, as they work in a "licensed reference laboratory." Specific certifications or experience years are not given.

4. Adjudication method for the test set

Not applicable. The ground truth is established by a definitive analytical method (GC/MS). There is no "adjudication" in the sense of reconciling disagreements among multiple human readers for an image-based or qualitative assessment. The GC/MS provides a quantitative concentration, which is then used to determine positive/negative relative to the cutoffs. Any "discordance" (like the one noted in the method comparison for Sample 51) is a direct comparison between the immunoassay result and the GC/MS result, not a result of human reader discrepancy requiring 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, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is an in vitro diagnostic (IVD) assay designed to provide an automated analytical result (qualitative or semi-quantitative concentration of EDDP). It is not an imaging AI device that assists human readers in interpreting medical images. Therefore, the concept of "human readers improve with AI vs without AI assistance" is not applicable here.

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

Yes, the primary performance evaluation is standalone. The ARK EDDP Assay is an automated immunoassay performed on clinical chemistry analyzers. The results (qualitative positive/negative or semi-quantitative concentration) are generated by the assay system (reagents + analyzer) without human interpretive input for the result itself. The results are then reported to a clinician for medical interpretation in conjunction with other clinical information. The precision, analytical recovery, specificity, interference, and method comparison studies all represent the "algorithm only" or "device only" performance.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The ground truth used is definitive analytical method (Gas Chromatography/Mass Spectrometry - GC/MS). For in vitro diagnostic assays measuring specific chemical compounds, GC/MS is considered the most accurate and reliable "truth" method.

8. The sample size for the training set

This document does not specify a separate "training set" sample size. For an immunoassay like the ARK EDDP Assay, the "training" (development and optimization) phase would involve numerous laboratory experiments to select reagents, optimize assay conditions, and establish initial performance characteristics. This is distinct from machine learning model training sets. The studies presented (precision, analytical recovery, specificity, interference, method comparison) are performance validation studies for the final device, not datasets used to train an algorithm.

9. How the ground truth for the training set was established

Not applicable in the context of an immunoassay. The "ground truth" for developing an immunoassay would be established by controlled spiking experiments using certified reference materials of the analyte (EDDP) in a known matrix (drug-free human urine), and confirming those concentrations using methods like GC/MS or LC-MS/MS, or by gravimetric/volumetric preparation. The goal is to ensure the assay accurately measures the target compound.

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The ARK Fentanyl Assay is an immunoasay intended for the qualitative detection of fentanyl in human urine at a cutoff concentration of 1.0 ng/mL. The assay is intended for use in laboratories with automated clinical chemistry analyzers. This in vitro diagnostic device is for prescription use only.

The ARK Fentanyl Assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry (GC/MS) or Liquid Chromatography/tandem Mass Spectrometry (LC-MS/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug test result, particularly when the prelininary test result is positive.

The ARK Fentanyl Assay is a homogeneous enzyme immunoassay technique used for the analysis of a specific compound in human urine. The assay is based on competition between drug in the specimen and drug labeled with recombinant glucose-6-phosphate dehydrogenase (rG6PDH) for antibody binding sites. As the latter binds antibody, enzyme activity decreases. In the presence of drug from the specimen, enzyme activity increases and is directly proportional to the drug concentration. Active enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH in the presence of glucose-6-phosphate (G6P), resulting in an absorbance change that is measured spectrophotometrically. Endogenous G6PDH does not interfere because the coenzyme NAD functions only with the bacterial enzyme used in the assay.

The ARK Fentanyl Assay consists of reagents R1 anti-fentanyl polyclonal antibody with substrate and R2 fentanyl derivative labeled with bacterial recombinant G6PDH enzyme.

The provided text describes the performance characteristics of the ARK Fentanyl Assay, an immunoassay for the qualitative detection of fentanyl in human urine. Here's a breakdown of the requested information based on the document:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly state "acceptance criteria" in a typical quantitative pass/fail table format for all parameters. Instead, it presents various performance studies with their results, implying that these results met the internal criteria for the manufacturer to claim substantial equivalence. The precision table comes closest to showing performance relative to a cutoff.

2. Sample size used for the test set and the data provenance

• Precision Test Set: Not explicitly stated as a separate "test set" but 160 analyses were performed for each of 9 fentanyl concentration levels, totaling 1440 analyses.
• Analytical Specificity / Interference Test Set: Concentrations of various compounds were spiked into drug-free, negative human urine. The number of individual urine samples used is not specified, but the testing was performed on Beckman Coulter AU680.
• Method Comparison Test Set: A total of 150 unaltered clinical urine specimens.
• Data Provenance: The document states "human urine" was used for testing, and for the method comparison, it specifies "unaltered clinical urine specimens that are not individually identifiable." No specific country of origin is mentioned, but the context implies it was likely conducted in the US, given the FDA submission. The studies appear to be prospective as they were specifically designed and conducted to evaluate the device's performance for this submission.

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

This section is not applicable as the device is an in-vitro diagnostic (IVD) immunoassay for detecting a chemical (fentanyl) in urine, not an image-based AI device requiring expert interpretation of medical images. The "ground truth" for the method comparison was established by a laboratory-based confirmatory method, LC-MS/MS (Liquid Chromatography/tandem Mass Spectrometry).

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

This is not applicable for this type of IVD device. Adjudication methods like "2+1" or "3+1" are typically used in medical imaging studies where human readers provide interpretations that need to be reconciled to establish a consensus ground truth. Here, the ground truth is an analytical measurement (LC-MS/MS).

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 is not applicable. The device is an automated immunoassay, which does not involve human readers for interpretation, nor is it an AI-assisted diagnostic tool. Its performance is compared against a gold-standard laboratory method (LC-MS/MS).

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

Yes, the studies presented (Precision, Analytical Specificity, Interference, and Method Comparison) represent the standalone performance of the ARK Fentanyl Assay, as it is an automated immunoassay performed on clinical chemistry analyzers, without human intervention for result interpretation beyond the machine's output. The device itself is the "algorithm only" in this context.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

The ground truth for the method comparison study was established by LC-MS/MS (Liquid Chromatography/tandem Mass Spectrometry), which is considered a definitive confirmatory chemical method for fentanyl detection.

8. The sample size for the training set

This information is not provided in the document. The document describes performance validation studies for the device, but it does not detail the internal development or "training" process (if any, in the context of an immunoassay optimization rather than machine learning). Immunoassays are biochemically developed systems, not typically "trained" on data sets in the same way an AI algorithm is.

9. How the ground truth for the training set was established

As the document does not describe a "training set" in the context of machine learning, this information is not applicable. The development of an immunoassay involves extensive biochemical research, optimization, and validation using well-characterized samples, rather than a data-driven "training" process with a ground truth dataset in the AI sense. The calibrators and controls used are prepared by volumetric dilution of high purity fentanyl traceable to HPLC into drug-free human urine.

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The ARK™ Methotrexate Assay is a homogeneous enzyme immunoassay intended for the quantitative determination of methotrexate in human serum or plasma on automated clinical chemistry analyzers. The measurements obtained are used in monitoring levels of methotrexate to help ensure appropriate therapy.

Specimens from patients who have received glucarpidase (carboxypeptidase G2) as a high dose methotrexate rescue therapy should not be tested with the ARK Methotrexate Assay.

The ARK Methotrexate Assay is a homogeneous immunoassay based on competition between drug in the specimen and Methotrexate labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for binding to the antibody reagent. As the latter binds antibody, enzyme activity decreases. In the presence of drug from the specimen, enzyme activity increases and is directly proportional to the drug concentration. Active enzyme converts the coenzyme nicotinamide adenine dinucleotide (NAD) to NADH that is measured spectrophotometrically as a rate of change in absorbance. Endogenous serum G6PDH does not interfere with the results because the coenzyme NAD functions only with the bacterial enzyme used in the assay.

The ARK Methotrexate Assay consists of reagents R1 anti-Methotrexate polyclonal antibody with substrate and R2 Methotrexate labeled with bacterial G6PDH enzyme. The ARK Methotrexate Calibrator consists of a six-level set to calibrate the assay, and the ARK Methotrexate Control consists of a six-level set used for quality control of the assay (tri-level calibration range set and tri-level high range set). The ARK Methotrexate Dilution Buffer is equivalent to zero calibrator (Calibrator A).

Here's an analysis of the provided text to extract the acceptance criteria and study information:

Acceptance Criteria and Device Performance for ARK™ Methotrexate Assay

The provided document describes the acceptance criteria and the study that proves the ARK™ Methotrexate Assay, when used on the Beckman Coulter AU680 analyzer, meets these criteria. The study aims to demonstrate substantial equivalence to the assay's performance on the predicate device, the Roche/Hitachi 917 analyzer.

1. Table of Acceptance Criteria and Reported Device Performance

The document states: "The pre-determined Pass/Fail acceptance criteria were met for all of the above performance studies." However, the specific numerical acceptance criteria or performance values for each characteristic are not provided in the given text. It only lists the types of performance characteristics evaluated.

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

The document does not specify the sample sizes used for the test set for any of the performance studies.

The document refers to "human serum or plasma" as the sample type. The country of origin of the data is not explicitly stated. The study is a "validation and verification" activity, implying it was conducted specifically for this submission, likely making it a prospective study for the purpose of device validation.

3. Number of Experts and Qualifications for Ground Truth

The concept of "experts" and their qualifications for establishing ground truth, as typically seen in image analysis or diagnostic interpretation, is not applicable to this type of in vitro diagnostic device (immunoassay) study. The ground truth for this device's performance characteristics is established through analytical methods and reference standards, not expert interpretation.

4. Adjudication Method for the Test Set

The concept of an "adjudication method" (e.g., 2+1, 3+1) is not applicable to this type of in vitro diagnostic device (immunoassay) study. Performance is assessed through quantitative measurements against established analytical criteria, not through expert consensus on diagnostic outcomes.

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

A Multi-Reader Multi-Case (MRMC) comparative effectiveness study is not applicable to this type of in vitro diagnostic device (immunoassay). This study design is typically used for imaging or diagnostic interpretation tasks where human readers' performance is being evaluated, often with and without AI assistance. This device is an automated assay, not an AI for human interpretive tasks.

6. Standalone (Algorithm Only) Performance Study

The study described is a standalone performance study for the algorithm (assay system) on the Beckman Coulter AU680 analyzer. The validation and verification activities listed (Limit of Blank, Limit of Detection, Accuracy, Precision, etc.) directly evaluate the performance of the device itself, without human interpretation in the loop. The purpose is to demonstrate that the assay system alone performs comparably to its predicate.

7. Type of Ground Truth Used

For an immunoassay like the ARK™ Methotrexate Assay, the "ground truth" for evaluating its performance characteristics (analytical accuracy, precision, linearity, etc.) would be established through:

• Reference materials/standards: Calibrators and controls with precisely known concentrations of methotrexate.
• Reference methods: Comparison with established, validated analytical methods (e.g., LC-MS/MS, or the predicate device's performance which was previously validated) for samples with unknown concentrations.
• Spiking studies: Adding known amounts of analyte to a sample and measuring recovery to assess accuracy.

The document implicitly refers to these as part of the "analytical performance studies" and "validation and verification activities."

8. Sample Size for the Training Set

The document does not mention a training set or its sample size. This is expected as the ARK™ Methotrexate Assay is a homogeneous enzyme immunoassay kit, not a machine learning or AI model that requires a "training set" in the conventional sense. The "training" for such a system would involve validating its components and establishing its operational parameters on the target analyzer.

9. How Ground Truth for the Training Set Was Established

Since there is no "training set" in the context of machine learning, this question is not applicable. The assay is a chemical and biological system where parameters are set based on chemical principles and reagent characteristics, and then validated through performance studies.

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The ARK™ Oxcarbazepine Metabolite Assay is a homogeneous enzyme immunoassay intended for the quantitative determination of Oxcarbazepine Metabolite in human serum on automated clinical chemistry analyzers. The measurements obtained are used in monitoring levels of Oxcarbazepine Metabolite to help ensure appropriate therapy.

The ARK™ Oxcarbazepine Metabolite Calibrator is intended for use in calibration of the ARK Oxcarbazepine Metabolite Assay.

The ARK™ Oxcarbazepine Metabolite Control is an assayed quality control material intended for use in quality control of the ARK Oxcarcarbazepine Metabolite Assay.

For prescription use only. Caution: Federal Law restricts this device to sale by or on the order of a licensed practitioner.

The ARK Oxcarbazepine Metabolite Assay is a homogeneous immunoassay based on competition between drug in the specimen and Oxcarbazepine Metabolite labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for binding to the antibody reagent. As the latter binds antibody, enzyme activity decreases. In the presence of drug from the specimen, enzyme activity increases and is directly proportional to the drug concentration. Active enzyme converts the coenzyme nicotinamide adenine dinucleotide (NAD) to NADH that is measured spectrophotometrically as a rate of change in absorbance. Endogenous serum G6PDH does not interfere with the results because the coenyzme NAD functions only with the bacterial enzyme used in the assay.

The ARK Oxcarbazepine Metabolite Assay consists of reagents R1 anti-Oxcarbazepine Metabolite polyclonal antibody with substrate and R2 Oxcarbazepine Metabolite labeled with bacterial G6PDH enzyme. The ARK Oxcarbazepine Metabolite Calibrator consists of a six-level set to calibrate the assay, and the ARK Oxcarbazepine Metabolite Control consists of a three-level set used for quality control of the assay.

The provided document describes the performance characteristics of the ARK™ Oxcarbazepine Metabolite Assay, Ark Oxcarbazepine Metabolite Calibrator, and Ark Oxcarbazepine Metabolite Control. This is a 510(k) premarket notification for a medical device (an in-vitro diagnostic assay), not an AI/ML powered device, therefore the information typically requested for AI/ML device studies (such as number of experts, adjudication methods, multi-reader multi-case studies, separate training/test sets with ground truth establishment methods for AI/ML models) are not applicable.

The acceptance criteria and performance data are detailed for several analytical validation studies.

Here's the breakdown of the requested information based on the provided document:

1. A table of acceptance criteria and the reported device performance

2. Sample size used for the test set and the data provenance

• LOQ: Not explicitly stated how many unique samples, but "mean of six (6) replicate measurements" for recovery at different enantiomer ratios.
• Recovery: Not explicitly stated how many unique samples, but "mean of six (6) replicate measurements" of Oxcarbazepine Metabolite was tabulated as a function of the enantiomer ratio.
• Linearity: Not explicitly stated how many unique samples other than a "60.0 µg/mL serum sample was prepared and dilutions were made proportionally."
• Method Comparison: 190 samples.
• Precision: 3 levels of ARK Control (N=160 each) and 3 human serum pooled specimens (N=160 each). This means for each of the 6 material types, 160 measurements were taken (quadruplicate twice a day for 20 days).
• Interfering Substances: Not explicitly stated the number of unique human serum samples, but substances were tested "in serum with known levels of Oxcarbazepine Metabolite (approximately 3 and 30 µg/mL)."
• Specificity & Drug Interference: Not explicitly stated how many unique human serum samples, but tested with spiked compounds into normal human serum with known Oxcarbazepine Metabolite levels.
• Sample Stability & Calibration Curve Stability: "supporting data" cited, but specific sample sizes are not provided within this document.

Data Provenance: The document does not specify the country of origin of the human serum samples. The studies are analytical validations performed retrospectively in a laboratory setting (e.g., Beckman Coulter AU480® automated clinical chemistry analyzer). It's not a prospective clinical trial with patient data.

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

This is an analytical chemistry assay validation, not a diagnostic imaging AI/ML model. Therefore, "experts" in the sense of physicians establishing ground truth for patient cases are not applicable. The "ground truth" for the test set (e.g., concentration of Oxcarbazepine Metabolite) is established by highly accurate reference methods such as LC-MS/MS (for method comparison) or by precise gravimetric/volumetric preparation of controls and calibrators using certified reference materials. The qualifications of the personnel performing these analytical tests are implicitly assumed to be those typical for a laboratory setting conducting such validations.

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

Not applicable. This is an analytical validation of an in-vitro diagnostic assay measuring a chemical concentration, not a study involving human readers or subjective interpretations requiring 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

Not applicable. This is an analytical validation of an in-vitro diagnostic assay, not an AI-assisted diagnostic device for human readers.

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

The device itself is an "algorithm only" in the sense that it is an automated chemical assay system. Its performance (quantification of Oxcarbazepine Metabolite) is assessed independently through the various analytical studies (e.g., LOQ, linearity, precision, method comparison against LC-MS/MS). Human "human-in-the-loop" performance is not a direct component of the assay's function, though human operators are involved in running the assay and interpreting the results.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

The "ground truth" for the analytical performance studies is primarily:

• Reference Method: For method comparison, LC-MS/MS (Liquid Chromatography-Mass Spectrometry/Mass Spectrometry) is used as the reference "ground truth" method. LC-MS/MS is a highly accurate and precise analytical technique for quantifying specific compounds in complex mixtures.
• Gravimetric/Volumetric Preparation: For calibrators and controls, the "ground truth" concentrations are established by precise gravimetric addition of certified Oxcarbazepine Metabolite powder to solvents. Purity is determined by NMR and elemental analysis.

8. The sample size for the training set

This is an immunoassay, not a machine learning or AI algorithm in the traditional sense that requires a "training set" for model development. The "training" of the assay refers to its calibration. The calibrators are prepared and value-assigned as described (e.g., "Two calibrated runs are performed using the Master Calibrator. In each run, five replicates of Master Lot (reference) and Test Lot are tested as matched pairs for each calibrator level.").

9. How the ground truth for the training set was established

As described above, for an immunoassay, the "training set" is the calibrator set. The ground truth for the calibrators is established through:

• Traceability to certified powder: The calibrators are traceable to certified Oxcarbazepine Metabolite powder. "The purity of Oxcarbazepine Metabolite in the certified raw material is determined by NMR and elemental analysis as performed by the supplier of the certified powder."
• Gravimetric Addition: "Bulk solutions of the ARK Oxcarbazepine Metabolite Calibrator are prepared volumetrically using a stock solution prepared by gravimetric addition of powder to solvent."
• Value Assignment: "Testing is performed with the ARK Oxcarbazepine Metabolite Assay on the Beckman Coulter AU480® automated analyzer. Two calibrated runs are performed using the Master Calibrator. In each run, five replicates of Master Lot (reference) and Test Lot are tested as matched pairs for each calibrator level. Mean values for ten replicates are calculated." This process ensures consistency and accuracy against a master reference.

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